Mental health interventions for individuals with serious mental illness in the criminal legal system: a systematic review.

BACKGROUND: Globally, individuals with mental illness get in contact with the law at a greater rate than the general population. The goal of this review was to identify and describe: (1) effectiveness of mental health interventions for individuals with serious mental illness (SMI) who have criminal legal involvement; (2) additional outcomes targeted by these interventions; (3) settings/contexts where interventions were delivered; and (4) barriers and facilitating factors for implementing these interventions. METHODS: A systematic review was conducted to summarize the mental health treatment literature for individuals with serious mental illness with criminal legal involvement (i.e., bipolar disorder, schizophrenia, major depressive disorder). Searches were conducted using PsychINFO, Embase, ProQuest, PubMed, and Web of Science. Articles were eligible if they were intervention studies among criminal legal involved populations with a mental health primary outcome and provided description of the intervention. RESULTS: A total of 13 eligible studies were identified. Tested interventions were categorized as cognitive/behavioral, community-based, interpersonal (IPT), psychoeducational, or court-based. Studies that used IPT-based interventions reported clinically significant improvements in mental health symptoms and were also feasible and acceptable. Other interventions demonstrated positive trends favoring the mental health outcomes but did not show statistically and clinically significant changes. All studies reported treatment outcomes, with only 8 studies reporting both treatment and implementation outcomes. CONCLUSION: Our findings highlight a need for more mental health research in this population. Studies with randomized design, larger sample size and studies that utilize non-clinicians are needed.

Recurrent Neuroendocrine Primary Cutaneous Mucinous Carcinoma of the Scalp After Complete Excision.

ABSTRACT: Primary cutaneous mucinous carcinoma is a rare, indolent malignancy with a debated history regarding cell of origin. Recurrence is rare but has been documented in up to a third of cases. Recent literature reviews have recognized 2 possible subtypes-neuroendocrine and nonneuroendocrine- with different possible prognostic implications for patients. We describe a case of recurrent primary cutaneous mucinous carcinoma in a 50-year-old man with subtle neuroendocrine features not initially recognized on routine H&E staining but highlighted by immunohistochemical studies. We underscore the importance of immunohistochemical use in these rare cases and emphasize that awareness of these neuroendocrine and nonneuroendocrine subtypes is essential for a complete diagnosis.

Evaluating the Response of Palbociclib on Progression-Free Survival in Hormone Receptor-Positive Metastatic Breast Cancer.

BACKGROUND: In patients with hormone receptor-positive metastatic breast cancer, palbociclib has been shown to improve overall survival and progression-free survival (PFS) when combined with endocrine therapy. Dose modification of palbociclib is effective in the management of adverse events. Despite variable clinical response, no predictive biomarkers of efficacy to palbociclib have been identified in metastatic breast cancer. In our study, we aimed to assess the PFS of metastatic breast cancer patients who received dose-reduced palbociclib and compare the results in the non-dose-reduced group. We also evaluated the clinical significance of progesterone receptor (PR) and Ki67 as predictive biomarkers of palbociclib. METHODS: Seventy-six palbociclib-treated metastatic breast cancer patients were included in our study. PFS was compared between dose-reduced and non-dose-reduced groups. PR expression and Ki67 status were assessed by immunohistochemistry. Kaplan-Meier method and log-rank test were used to analyze PFS. RESULTS: Of the 76 patients, 40 (52.6%) experienced dose reduction (DR). Statistical analysis of the results revealed that there were no statistically significant differences observed between dose-reduced (16.5 months) versus non-dose-reduced (17.7 months) patients in PFS (p = 0.5493). For patients with Ki67 ≥14%, PFS was 15.2 months (95% CI: 10.2-22.2 months; p = 0.3024). In patients with PR ≥20%, median PFS was 25.0 months (lower 95% CI: 16.8 months; p = 0.0069). CONCLUSION: Our study indicated that DR of palbociclib is frequently required but does not appear to affect PFS. PR expression was suggested to be a significant predictive factor for palbociclib responsiveness.

Access to Substituted Indenol Ethers via a Regioselective Intermolecular Carbopalladation Cascade.

Alkyne carbopalladation reactions can rapidly generate multiple new C-C bonds; however, regioselectivity is challenging for intermolecular variants. Using ynol ethers, we observe complete regiocontrol of migratory insertion followed by a second migratory insertion with a pendant alkene to turn-over the catalytic cycle. The resulting products are oligosubstituted 1-indenol ethers with defined stereochemistry based on the initial alkene geometry. Blocking ß-hydride elimination allowed for C-H and C-C reductive elimination steps for catalyst turnover.

Accessing 4-oxy-substituted isoquinolinones via C-H activation and regioselective migratory insertion with electronically biased ynol ethers.

The rhodium-catalyzed C-H activation and annulation with ynol ethers to directly provide 4-oxy substituted isoquinolinones is reported. The polarized nature of ynol ethers provides an electronic bias for controlling the regioselectivity of the migratory insertion process. While the highly reactive nature of ynol ethers presents a challenge, mild conditions were found to provide product in moderate to good yield. Utility was demonstrated by application in the synthesis of a prolyl-4-hydroxylase inhibitor framework.

Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity.

All pancreatic endocrine cell types arise from a common endocrine precursor cell population, yet the molecular mechanisms that establish and maintain the unique gene expression programs of each endocrine cell lineage have remained largely elusive. Such knowledge would improve our ability to correctly program or reprogram cells to adopt specific endocrine fates. Here, we show that the transcription factor Nkx6.1 is both necessary and sufficient to specify insulin-producing beta cells. Heritable expression of Nkx6.1 in endocrine precursors of mice is sufficient to respecify non-beta endocrine precursors towards the beta cell lineage, while endocrine precursor- or beta cell-specific inactivation of Nkx6.1 converts beta cells to alternative endocrine lineages. Remaining insulin(+) cells in conditional Nkx6.1 mutants fail to express the beta cell transcription factors Pdx1 and MafA and ectopically express genes found in non-beta endocrine cells. By showing that Nkx6.1 binds to and represses the alpha cell determinant Arx, we identify Arx as a direct target of Nkx6.1. Moreover, we demonstrate that Nkx6.1 and the Arx activator Isl1 regulate Arx transcription antagonistically, thus establishing competition between Isl1 and Nkx6.1 as a critical mechanism for determining alpha versus beta cell identity. Our findings establish Nkx6.1 as a beta cell programming factor and demonstrate that repression of alternative lineage programs is a fundamental principle by which beta cells are specified and maintained. Given the lack of Nkx6.1 expression and aberrant activation of non-beta endocrine hormones in human embryonic stem cell (hESC)-derived insulin(+) cells, our study has significant implications for developing cell replacement therapies.

Study protocol for the ROSE Scale-Up Study: Informing a decision about ROSE as universal postpartum depression prevention.

PURPOSE: To examine the effectiveness, cost-outcome, equity, scalability, and mechanisms of the Reach Out, Stay strong, Essentials for mothers of newborns (ROSE) postpartum depression prevention (PPD) program as universal versus selective or indicated prevention. BACKGROUND: The United States Preventive Services Task Force (USPSTF) currently recommends PPD prevention for pregnant people at risk of PPD (i.e., selective/indicated prevention). However, universal prevention may be more scalable, equitable, and cost-beneficial. DESIGN: Effectiveness of ROSE for preventing PPD among people at risk is known. To assess ROSE as universal prevention, we need to determine the effectiveness of ROSE among all pregnant people, including those screening negative for PPD risk. We will enroll 2320 pregnant people, assess them with commonly available PPD risk prediction tools, randomize everyone to ROSE or enhanced care as usual, and assess ROSE as universal, selective, and indicated prevention in terms of: (1) effectiveness (PPD prevention and functioning), (2) cost-benefit, (3) equity (PPD cases prevented by universal prevention that would not be prevented under selective/indicated for minority vs. non-Hispanic white people), (4) quantitative and qualitative measures of scalability (from 98 agencies previously implementing ROSE), (5) ROSE mechanisms across risk levels. We will integrate results to outline pros and cons of the three prevention approaches (i.e., universal, selective, indicated). CONCLUSION: This will be the first trial to assess universal vs. selective/indicated PPD prevention. Trial design illustrates a novel, efficient way to make these comparisons. This trial, the largest PPD prevention trial to date, will examine scalability, an understudied area of implementation science.

Multifunctional Nanogenerator-Integrated Metamaterial Concrete Systems for Smart Civil Infrastructure.

Creating multifunctional concrete materials with advanced functionalities and mechanical tunability is a critical step toward reimagining the traditional civil infrastructure systems. Here, the concept of nanogenerator-integrated mechanical metamaterial concrete is presented to design lightweight and mechanically tunable concrete systems with energy harvesting and sensing functionalities. The proposed metamaterial concrete systems are created via integrating the mechanical metamaterial and nano-energy-harvesting paradigms. These advanced materials are composed of reinforcement auxetic polymer lattices with snap-through buckling behavior fully embedded inside a conductive cement matrix. We rationally design their composite structures to induce contact-electrification between the layers under mechanical excitations/triggering. The conductive cement enhanced with graphite powder serves as the electrode in the proposed systems, while providing the desired mechanical performance. Experimental studies are conducted to investigate the mechanical and electrical properties of the designed prototypes. The metamaterial concrete systems are tuned to achieve up to 15% compressibility under cycling loading. The power output of the nanogenerator-integrated metamaterial concrete prototypes reaches 330 µW. Furthermore, the self-powered sensing functionality of the nanogenerator concrete systems for distributed health monitoring of large-scale concrete structures is demonstrated. The metamaterial concrete paradigm can possibly enable the design of smart civil infrastructure systems with a broad range of advanced functionalities.

Targeted inhibition of telomerase activity combined with chemotherapy demonstrates synergy in eliminating ovarian cancer spheroid-forming cells.

OBJECTIVE: Telomerase activity (TA) is often used as a molecular marker for cancer aggressiveness. Our objectives were to determine the TA in ovarian cancer cell lines and the effectiveness of targeting telomerase for cancer therapy. METHODS: Ovarian cancer cell lines of various histologic subtypes were chosen to correspond to decreasing levels of clinical aggressiveness. Cells were grown in non-adherent growth conditions to form spheroid-forming cells (SFC). Telomerase activity was quantified using the TRAPeze RT Telomerase Detection Kit and confirmed with luciferase reporter plasmid containing promoter of human telomerase reverse transcriptase (hTERT). Cell proliferation survival assays were performed after treatment with a small molecule telomerase inhibitor BIBR1532 both with and without multiple chemotherapeutic agents. RESULTS: Compared to monolayer, TA from SFC correlated to the innate clinical aggressiveness of ovarian cancer cell lines ES2, SKOV3, and TOV112D. Treatment with BIBR1532 resulted in up to a 12-fold decrease in TA compared to controls. SFCs were significantly more resistant to BIBR1532 compared to monolayer cell lines; however, it showed reasonable efficacy at 100 uM. In combination assays, the addition of BIBR1532 to carboplatin yielded the most favorable results in regards to synergy in all three cell lines evaluated. CONCLUSIONS: Telomerase activity appears to correlate to the clinical aggressiveness seen in histologic subtypes of ovarian cancer. BIBR1532 demonstrated significant inhibition of TA as well as reasonable efficacy as a single agent. Inhibition of telomerase with BIBR1532 in combination with carboplatin demonstrated a more than additive effect in-vitro and could represent a novel targeted therapy for ovarian cancer.

Initially High Correlation between Air Pollution and COVID-19 Mortality Declined to Zero as the Pandemic Progressed: There Is No Evidence for a Causal Link between Air Pollution and COVID-19 Vulnerability.

Wu et al. found a strong positive association between cumulative daily county-level COVID-19 mortality and long-term average PM2.5 concentrations for data up until September 2020. We replicated the results of Wu et al. and extended the analysis up until May 2022. The association between PM2.5 concentration and cumulative COVID-19 mortality fell sharply after September 2020. Using the data available from Wu et al.'s "updated_data" branch up until May 2022, we found that the effect of a 1 µg/m3 increase in PM2.5 was associated with only a +0.603% mortality difference. The 95% CI of this difference was between -0.560% and +1.78%, narrow bounds that include zero, with the upper bound far below the Wu et al. estimate. Short-term trends in the initial spread of COVID-19, not a long-term epidemiologic association, caused an early correlation between air pollution and COVID-19 mortality.

Protocol for the Healing After Loss (HeAL) Study: a randomised controlled trial of interpersonal psychotherapy (IPT) for major depression following perinatal loss.

INTRODUCTION: This protocol describes a study testing the efficacy of interpersonal psychotherapy (IPT) for major depressive disorder following perinatal loss (early and late fetal death and early neonatal death). Perinatal loss is associated with elevated risk of major depressive disorder and post-traumatic stress disorder (PTSD). Perinatal loss conveys specific treatment needs. The trial will be the first fully powered randomised trial of treatment for any psychiatric disorder following perinatal loss. METHODS AND ANALYSIS: A sample of 274 women in Flint and Detroit areas in Michigan who experience a major depressive episode following a perinatal loss will be randomised to group IPT for perinatal loss or to group coping with depression. We anticipate that 50% of the sample will have co-occurring PTSD. Assessments occur at baseline, mid-treatment (8 weeks), post-treatment (16 weeks) and follow-up (28 weeks). Clinical outcomes include time to recovery from major depressive episode (primary), depressive symptoms, PTSD symptoms and time to recovery from PTSD. Additional outcomes include social support, social role functioning (including parental functioning for those with living children), well-being, grief (including complicated grief and fault beliefs) and fear of subsequent pregnancies. Social support and grief are hypothesised mediators of IPT effects on time to recovery from major depressive episode. ETHICS AND DISSEMINATION: The trial was approved by Michigan State University's Biomedical Institutional Review Board. It has a data and safety monitoring board and has been submitted to the community-based organisation partners community ethics review board. Written operating procedures outline methods for protecting confidentiality, monitoring and recording adverse events, and safeguarding participants. We will share study results with research and clinical communities, community organisations through which we recruited, and will offer results to study participants. Deidentified datasets will be available through the National Institute of Mental Health Data Archive and to qualified investigators on request. TRIAL REGISTRATION NUMBER: NCT04629599.

EndoBind detects endogenous protein-protein interactions in real time.

We present two high-throughput compatible methods to detect the interaction of ectopically expressed (RT-Bind) or endogenously tagged (EndoBind) proteins of interest. Both approaches provide temporal evaluation of dimer formation over an extended duration. Using examples of the Nrf2-KEAP1 and the CRAF-KRAS-G12V interaction, we demonstrate that our method allows for the detection of signal for more than 2 days after substrate addition, allowing for continuous monitoring of endogenous protein-protein interactions in real time.

Identification of a small molecule that stimulates human ß-cell proliferation and insulin secretion, and protects against cytotoxic stress in rat insulinoma cells.

A key event in the development of both major forms of diabetes is the loss of functional pancreatic islet ß-cell mass. Strategies aimed at enhancing ß-cell regeneration have long been pursued, but methods for reliably inducing human ß-cell proliferation with full retention of key functions such as glucose-stimulated insulin secretion (GSIS) are still very limited. We have previously reported that overexpression of the homeobox transcription factor NKX6.1 stimulates ß-cell proliferation, while also enhancing GSIS and providing protection against ß-cell cytotoxicity through induction of the VGF prohormone. We developed an NKX6.1 pathway screen by stably transfecting 832/13 rat insulinoma cells with a VGF promoter-luciferase reporter construct, using the resultant cell line to screen a 630,000 compound chemical library. We isolated three compounds with consistent effects to stimulate human islet cell proliferation, but not expression of NKX6.1 or VGF, suggesting an alternative mechanism of action. Further studies of the most potent of these compounds, GNF-9228, revealed that it selectively activates human ß-cell relative to α-cell proliferation and has no effect on δ-cell replication. In addition, pre-treatment, but not short term exposure of human islets to GNF-9228 enhances GSIS. GNF-9228 also protects 832/13 insulinoma cells against ER stress- and inflammatory cytokine-induced cytotoxicity. GNF-9228 stimulates proliferation via a mechanism distinct from recently emergent DYRK1A inhibitors, as it is unaffected by DYRK1A overexpression and does not activate NFAT translocation. In conclusion, we have identified a small molecule with pleiotropic positive effects on islet biology, including stimulation of human ß-cell proliferation and insulin secretion, and protection against multiple agents of cytotoxic stress.

A Dual Inhibitor of DYRK1A and GSK3ß for ß-Cell Proliferation: Aminopyrazine Derivative GNF4877.

Loss of ß-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase ß-cell mass are less developed. Promoting ß-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring ß-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3ß (GSK3ß) was previously reported to induce primary human ß-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring ß-cell proliferation.

Integrated In Vivo Quantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic ß Cell Function.

Pancreatic ß cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion. Nutrient tracing and targeted metabolomics demonstrated accelerated accumulation of glucose-derived metabolites and coupling factors in islets from 1-year-old mice, indicating that age-related changes in glucose metabolism contribute to improved glucose-stimulated insulin secretion with age. Together, our study provides an in-depth characterization of age-related changes in the islet proteome and establishes metabolic rewiring as an important mechanism for age-associated changes in ß cell function.

Osseous Healing in Foot and Ankle Surgery with Autograft, Allograft, and Other Orthobiologics.

In the surgical treatment of foot and ankle abnormality, many problems require bone grafting for successful osseous union. Nonunion, reconstruction, and arthrodesis procedures pose specific challenges due to bony defects secondary to trauma, malunions, or previous surgery. Nonunion in foot and ankle arthrodesis is a significant risk and is well documented in recent literature. This article is a review of the recent literature regarding the use of bone graft and orthobiologics in foot and ankle surgery.

Bilateral femoral neck fractures associated with complex pelvic ring injuries in a pediatric patient: a case report.

Femoral neck and pelvic fractures are rarely encountered in the pediatric population secondary to the resilient nature of the immature skeleton. Both fracture types usually result from high-energy blunt trauma including motor vehicle collisions, motor vehicle-pedestrian accidents, and falls from height. Considerable studies have been published on the natural history, management, and complications of pediatric pelvis and femoral neck fractures. However, few case reports have documented both fracture types in the same patient. Management of concomitant injuries presents unique challenges both for operative stabilization and for clinical postoperative care. After appropriate consent was obtained, a thorough review was performed of the patient's hospital records and imaging history. The senior author of the report also provided insight into the management of the patient's initial injuries and subsequent complications. Our case involves a 4-year-old female who was overrun by an all-terrain vehicle. Her orthopedic injuries included a nondisplaced Delbet type 3 fracture of the right femoral neck, a completely displaced Delbet type 3 fracture of the left femoral neck, bilateral sacroiliac fracture-dislocations, severe comminution of her left pubic rami, and a free-floating right pubic rami segment spanning from the triradiate cartilage to the pubic symphysis with severe rotational deformity. Her postoperative recovery was complicated by refracture of her left femoral neck (Delbet type 1), left hip osteomyelitis, and left femoral head avascular necrosis. The salient features of her operative management, subsequent complications, and functional recovery are described in this report. Cases of bilateral femoral neck fractures and multiple pelvic fractures in pediatric patients are sparsely documented in the literature because of their infrequent occurrence. Pediatric pelvic fractures typically do well with conservative treatment secondary to the incredible remodeling ability of the immature pelvis. Femoral neck fractures, in contrast, are highly associated with complications including coxa vara, nonunion, infection, physeal closure, and avascular necrosis. This case report documents two rare fracture types in the same patient and describes the challenges encountered throughout the duration of her recovery. LEVEL OF EVIDENCE: Level V, Case report.

LIM domain-binding 1 maintains the terminally differentiated state of pancreatic ß cells.

The recognition of ß cell dedifferentiation in type 2 diabetes raises the translational relevance of mechanisms that direct and maintain ß cell identity. LIM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes promoter-enhancer looping, thereby directing fate assignment and maturation of progenitor populations. Many terminally differentiated endocrine cell types, however, remain enriched for LDB1, but its role is unknown. Here, we have demonstrated a requirement for LDB1 in maintaining the terminally differentiated status of pancreatic ß cells. Inducible ablation of LDB1 in mature ß cells impaired insulin secretion and glucose homeostasis. Transcriptomic analysis of LDB1-depleted ß cells revealed the collapse of the terminally differentiated gene program, indicated by a loss of ß cell identity genes and induction of the endocrine progenitor factor neurogenin 3 (NEUROG3). Lineage tracing confirmed that LDB1-depleted, insulin-negative ß cells express NEUROG3 but do not adopt alternate endocrine cell fates. In primary mouse islets, LDB1 and its LIM homeodomain-binding partner islet 1 (ISL1) were coenriched at chromatin sites occupied by pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), forkhead box A2 (FOXA2), and NK2 homeobox 2 (NKX2.2) - factors that co-occupy active enhancers in 3D chromatin domains in human islets. Indeed, LDB1 was enriched at active enhancers in human islets. Thus, LDB1 maintains the terminally differentiated state of ß cells and is a component of active enhancers in both murine and human islets.

Computational analysis of swallowing mechanics underlying impaired epiglottic inversion.

OBJECTIVES/HYPOTHESIS: Determine swallowing mechanics associated with the first and second epiglottic movements, that is, movement to horizontal and full inversion, respectively, to provide a clinical interpretation of impaired epiglottic function. STUDY DESIGN: Retrospective cohort study. METHODS: A heterogeneous cohort of patients with swallowing difficulties was identified (n = 92). Two speech-language pathologists reviewed 5-mL thin and 5-mL pudding videofluoroscopic swallow studies per subject, and assigned epiglottic component scores of 0 = complete inversion, 1 = partial inversion, and 2 = no inversion, forming three groups of videos for comparison. Coordinates mapping minimum and maximum excursion of the hyoid, pharynx, larynx, and tongue base during pharyngeal swallowing were recorded using ImageJ software. A canonical variate analysis with post hoc discriminant function analysis of coordinates was performed using MorphoJ software to evaluate mechanical differences between groups. Eigenvectors characterizing swallowing mechanics underlying impaired epiglottic movements were visualized. RESULTS: Nineteen of 184 video swallows were rejected for poor quality (n = 165). A Goodman-Kruskal index of predictive association showed no correlation between epiglottic component scores and etiologies of dysphagia (λ = .04). A two-way analysis of variance by epiglottic component scores showed no significant interaction effects between sex and age (f = 1.4, P = .25). Discriminant function analysis demonstrated statistically significant mechanical differences between epiglottic component scores: 1 and 2, representing the first epiglottic movement (Mahalanobis distance = 1.13, P = .0007); and 0 and 1, representing the second epiglottic movement (Mahalanobis distance = 0.83, P = .003). Eigenvectors indicate that laryngeal elevation and tongue base retraction underlie both epiglottic movements. CONCLUSIONS: Results suggest that reduced tongue base retraction and laryngeal elevation underlie impaired first and second epiglottic movements. The styloglossus, hyoglossus, and long pharyngeal muscles are implicated as targets for rehabilitation in dysphagic patients with impaired epiglottic inversion. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1854-1858, 2016.

Postnatal ß-cell proliferation and mass expansion is dependent on the transcription factor Nkx6.1.

All forms of diabetes are characterized by a loss of functional ß-cell mass, and strategies for expanding ß-cell mass could have significant therapeutic benefit. We have recently identified the transcription factor Nkx6.1 as an essential maintenance factor of the functional ß-cell state. In addition, Nkx6.1 has been proposed to control ß-cell proliferation, but a role for Nkx6.1 in regulating ß-cell mass has not been demonstrated. Here, we show that Nkx6.1 is required for postnatal ß-cell mass expansion. Genetic inactivation of Nkx6.1 in newly formed ß-cells caused a drastic decrease in early postnatal ß-cell proliferation, leading to reduced ß-cell mass and glucose intolerance. Interestingly, Nkx6.1 was dispensable for prenatal ß-cell proliferation. We found that Nkx6.1 regulates the expression of several ß-cell maturation markers as well as expression of the nutrient sensors Glut2 and Glp1r. Manifestation of the ß-cell mass defect at the transition to postnatal feeding suggests that Nkx6.1 could regulate ß-cell growth by enabling ß-cells to respond to nutrient-dependent proliferation signals, such as glucose and Glp1. Identification of ß-cell-intrinsic regulators that connect nutrient-sensing and proliferation suggests new therapeutic targets for expanding functional ß-cell mass.