Early cataract surgery and affordable Sinskey hook goniotomy in Black and Afro-Latino glaucoma patients: a 6-month retrospective study.

Aim: The purpose of this study was to determine the real-world efficacy of early phacoemulsification cataract surgery and goniotomy with a Sinskey hook in patients with glaucoma. Methods: This study was conducted at Advanced Eye Care of New York, a private practice located in Manhattan, NY. This was a single-center, retrospective study of predominantly Black and Afro-Latino patients with glaucoma. These patients underwent early phacoemulsification cataract surgery and goniotomy using an affordable and reusable straight Sinskey hook (Ambler 200-µm tip). Patients who underwent the aforementioned procedure with 6 months of follow-up were included in this study. Investigated parameters were intraocular pressure, number of medications, mean deviation on visual field test, visual acuity, adverse events, and pre/postoperative spherical refractive error. Results: Among all 38 eyes that were enrolled in the study and underwent surgery (goniotomy using a Sinskey hook with phacoemulsification), mean intraocular pressure was reduced from 16.45 mmHg at baseline to 13.24 mmHg at month 6, a 19.5% reduction. The mean number of topical intraocular pressure-lowering medications used was reduced from 1.81 at baseline to 0.52 at month 6, a 71% reduction in topical medications. Conclusion: Combined early cataract surgery and goniotomy performed with a Sinskey hook is an affordable microinvasive surgery and an effective way to reduce intraocular pressure and the number of ocular hypertensive medications used in Black and Afro-Latino patients with primary open-angle glaucoma.

Treating young adult cannabis use disorder with text message-delivered peer network counseling.

BACKGROUND: Approximately 16.5% of U.S. young adults have a cannabis use disorder (CUD) and are at risk for negative outcomes. Treatment can reduce cannabis use, but young adults are less likely to seek help than older adults. Peer Network Counseling-txt (PNC-txt) is a brief, text-delivered, Motivational Interviewing-informed substance use intervention focusing on peer relations and activity spaces as mechanisms for behavioral change. PNC-txt has shown evidence of reducing tobacco and cannabis use with adolescents and young adults, but it has not been tested in the context of legal cannabis use. The current randomized controlled trial sought to expand the evidence regarding the context of PNC-txt effects, comparing one state in which cannabis is legal (Colorado) and one state in which it is not (Tennessee). We hypothesized that participants randomized to PNC-txt would show significant reductions in cannabis use compared to controls, with larger reductions for females and those in Colorado, and that peer relations and activity space would mediate effects. METHODS: One thousand, seventy eight 18-25 year olds (CO: 551; TN: 527) who met screening criteria for CUD and biologically-verified cannabis use were randomly assigned to PNC-txt or waitlist control condition. Every other day for 4 weeks, participants assigned to PNC-txt received pre-programmed text conversations, tailored via data from the baseline assessment. Self-report and biological indicators of cannabis use were measured at 1-, 3-, and 6-months. DISCUSSION: Data analysis is underway. Results will provide evidence regarding whether, and how, PNC-txt reduces cannabis use in young adults with CUD. TRIAL REGISTRATION: This trial was prospectively registered on September 28, 2020 with ClinicalTrials.gov (NCT04567394).

Corrigendum: Pilot report: objective quantification of trabecular meshwork pigmentation using densitometry and the NIDEK GS-1 gonioscope in glaucoma patients.

[This corrects the article DOI: 10.3389/fopht.2023.1322178.].

Anesthetic dilemmas in an achondroplastic patient undergoing elective cesarean section.

Achondroplasia is a genetic condition characterized by skeletal dysplasia that results in characteristic craniofacial and spinal abnormalities. It is the most common form of short-limbed skeletal dysplasia. Additionally, a pregnant patient who is morbidly obese warrants specific anatomical and physiological considerations, such as a difficult airway with potential hypoxia, full stomach precautions, and a reduced functional residual capacity. Achondroplasia increases the risks of maternal and fetal complications. Although neuraxial techniques are generally preferred for cesarean sections, there is no consensus among patients with achondroplasia. We aimed to discuss the anesthetic challenges in an achondroplastic patient and report our regional anesthesia approach for an elective cesarean section.

Navigating the Adipocyte Precursor Niche: Cell-Cell Interactions, Regulatory Mechanisms and Implications for Adipose Tissue Homeostasis.

Support for stem cell self-renewal and differentiation hinges upon the intricate microenvironment termed the stem cell 'niche'. Within the adipose tissue stem cell niche, diverse cell types, such as endothelial cells, immune cells, mural cells, and adipocytes, intricately regulate the function of adipocyte precursors. These interactions, whether direct or indirect, play a pivotal role in governing the balance between self-renewal and differentiation of adipocyte precursors into adipocytes. The mechanisms orchestrating the maintenance and coordination of this niche are still in the early stages of comprehension, despite their crucial role in regulating adipose tissue homeostasis. The complexity of understanding adipocyte precursor renewal and differentiation is amplified due to the challenges posed by the absence of suitable surface receptors for identification, limitations in creating optimal ex vivo culture conditions for expansion and constraints in conducting in vivo studies. This review delves into the current landscape of knowledge surrounding adipocyte precursors within the adipose stem cell niche. We will review the identification of adipocyte precursors, the cell-cell interactions they engage in, the factors influencing their renewal and commitment toward adipocytes and the transformations they undergo during instances of obesity.

Opioid Use Disorder among Hospitalized Adults in North Carolina: Analysis from the 2000-2020 NC State Inpatient Database.

OBJECTIVES: Opioid use disorder (OUD) is characterized as a chronic condition that was first outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and now the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision. It encompasses frequent opioid usage, cravings, the development of tolerance, withdrawal symptoms upon discontinuation, unsuccessful attempts to quit or reduce use, and recurrent use even when faced with negative consequences. Both national- and state-level data show that overdose deaths associated with prescription opioids are increasing at an alarming rate. The increasing overdose deaths from illicitly manufactured fentanyl and other synthetic opioids compound this epidemic's burden. The present study sought to determine the prevalence and potential factors associated with OUD in North Carolina. METHODS: Using the State Inpatient Database, a retrospective cross-sectional study was conducted to identify OUD-related discharges between 2000 and 2020. Descriptive statistics and rates of OUD per 1000 discharges were calculated. Simple and multivariable logistic regression models were used to identify factors associated with increased odds of having an opioid use disorder diagnosis at discharge. The deviance-Pearson goodness of fit statistic was also used. Variables were identified using International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, Clinical Modification, codes in the discharge records. RESULTS: Of 19,370,483 hospitalizations that occurred between 2000 and 2020 in North Carolina, 483,250 were associated with OUD, a prevalence rate of 24.9 cases per 1000 discharges. The highest OUD rates were seen among adults who self-paid for their hospitalization, those with Medicaid, and those with other types of payors such as Workers' Compensation and the Indian Health Service; individuals between 25 and 54 years old; tobacco and alcohol users; Native American patients; patients located in urban areas; patients with lower household income; White patients; and female patients. OUD also was associated with increased odds of having one or more comorbid psychiatric disorders when controlling for other factors. CONCLUSIONS: Although preventive measures are crucial, including policies that discourage prescribing opioids for noncancer pain and those that target the manufacturing and distribution of synthetic opioids, providing integrated care for patients with OUD and co-occurring psychiatric and/or physical disorders is equally important. These findings suggest the need for a system-wide public health response focused on the expansion of primary prevention and treatment efforts, including crisis services, harm reduction services, and recovery programs.

Cost analysis of one-time intravenous antibiotic doses in the emergency department.

BACKGROUND: Research shows that one-time doses of intravenous (IV) antibiotics do not improve resolution of infection. Providers, however, continue to use them - especially in the emergency department. Very few studies have aimed to quantify the cost of this practice. OBJECTIVES: The primary objective was to evaluate the difference in average total cost of emergency department (ED) stay between patients who received a one-time dose of intravenous antibiotics in the ED before discharging on oral antibiotics and patients who were just discharged on oral antibiotics. Secondary objectives were to evaluate the differences in durations of stay between the two groups, as well as the differences in adverse drug effects and need for healthcare contact after discharge. METHODS: Chart review was conducted to identify patients who received and did not receive a one-time dose of IV antibiotics in the ED between April 30, 2020, and April 30, 2022. A micro-costing approach was used to determine ED-associated costs per patient. Comparisons in primary and secondary outcomes were performed using statistical inferential tests. RESULTS: A total of 102 patients were analyzed in each group. Patients who received a one-time dose of intravenous antibiotics in the emergency department before being discharged on oral antibiotics had an average length of stay of 4.55 hours, as opposed to patients who did not receive a one-time dose of intravenous antibiotics before being discharged on oral antibiotics who had an average length of stay of 2.82 hours (absolute difference: 1.73 hours, p < 0.001). One-time dosing of intravenous antibiotics in the emergency department incurred an additional cost of approximately $556 per patient, totaling to over $56,000 in our study cohort. CONCLUSION: The use of one-time intravenous antibiotics in the emergency department did not confer any additional benefits to patients. Use of one-time doses resulted in significantly reduced throughput in the emergency department and significantly increased healthcare costs.

Alloyed Airways: Chromium, Beryllium, and Titanium in the Lungs of an Aerospace Veteran.

Pneumoconiosis is a form of interstitial lung disease (ILD) that commonly occurs secondary to occupational or environmental exposures. This is an emerging disease as there are many potential forms of pathologic insults. Further adding to the complication is that clinical symptomatology secondary to pneumoconiosis can have long latent periods, as repetitive exposure over years leads to long-standing inflammation and subsequent irreversible damage. Exposure to asbestos, coal, silica, aluminum, talc, hay, and many more agents has the potential to cause pneumoconiosis. This case highlights a veteran, who made his career working with heavy metals such as chromium, beryllium, and titanium in the aerospace defense industry. This case discusses high-risk occupations, a workup for suspected pneumoconiosis, management, and the mechanism of lung injury underlying the three aforementioned pathologic agents. In each case of pneumoconiosis, a thorough history is essential, and diagnoses are made via the incorporation of the patient's historical risk factors, pulmonary function test (PFT) findings, and high-resolution chest computed tomography (HRCT).

Computational approaches for mechanobiology in cardiovascular development and diseases.

The cardiovascular development in vertebrates evolves in response to genetic and mechanical cues. The dynamic interplay among mechanics, cell biology, and anatomy continually shapes the hydraulic networks, characterized by complex, non-linear changes in anatomical structure and blood flow dynamics. To better understand this interplay, a diverse set of molecular and computational tools has been used to comprehensively study cardiovascular mechanobiology. With the continual advancement of computational capacity and numerical techniques, cardiovascular simulation is increasingly vital in both basic science research for understanding developmental mechanisms and disease etiologies, as well as in clinical studies aimed at enhancing treatment outcomes. This review provides an overview of computational cardiovascular modeling. Beginning with the fundamental concepts of computational cardiovascular modeling, it navigates through the applications of computational modeling in investigating mechanobiology during cardiac development. Second, the article illustrates the utility of computational hemodynamic modeling in the context of treatment planning for congenital heart diseases. It then delves into the predictive potential of computational models for elucidating tissue growth and remodeling processes. In closing, we outline prevailing challenges and future prospects, underscoring the transformative impact of computational cardiovascular modeling in reshaping cardiovascular science and clinical practice.

Drug-Induced Liver Injury Secondary to Terbinafine Use.

Drug-induced liver injury (DILI) has a symptomatic profile that mimics many forms of hepatic injury. In patients presenting with symptoms suspicious of acute liver injury, it is important that clinicians effectively rule out more common causes while simultaneously maintaining a broad differential diagnosis that includes DILI. In this report, we present the case of a 41-year-old African American male who was admitted to the hospital for two weeks' duration of worsening jaundice, right upper quadrant pain, pruritus, and acholic stools after terbinafine use for an acute episode of onychomycosis. Physical examination showed evidence of jaundice, scleral icterus, and a soft non-distended abdomen. Initial laboratory results at admission showed significant elevation of total bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. Careful review of the patient's medications, a clinical workup to rule out primary causes of hepatobiliary pathology, and confirmatory liver biopsy showing benign hepatic parenchyma with marked cholestasis including bile plugs and bile granulomas provided sufficient evidence supporting terbinafine use as the inciting factor. The emphasis of this case is to highlight the symptoms, diagnostic measures, and suspected pathophysiology of terbinafine-induced hepatotoxicity.

A Modular Framework for Implicit 3D-0D Coupling in Cardiac Mechanics.

In numerical simulations of cardiac mechanics, coupling the heart to a model of the circulatory system is essential for capturing physiological cardiac behavior. A popular and efficient technique is to use an electrical circuit analogy, known as a lumped parameter network or zero-dimensional (0D) fluid model, to represent blood flow throughout the cardiovascular system. Due to the strong physical interaction between the heart and the blood circulation, developing accurate and efficient numerical coupling methods remains an active area of research. In this work, we present a modular framework for implicitly coupling three-dimensional (3D) finite element simulations of cardiac mechanics to 0D models of blood circulation. The framework is modular in that the circulation model can be modified independently of the 3D finite element solver, and vice versa. The numerical scheme builds upon a previous work that combines 3D blood flow models with 0D circulation models (3D fluid - 0D fluid). Here, we extend it to couple 3D cardiac tissue mechanics models with 0D circulation models (3D structure - 0D fluid), showing that both mathematical problems can be solved within a unified coupling scheme. The effectiveness, temporal convergence, and computational cost of the algorithm are assessed through multiple examples relevant to the cardiovascular modeling community. Importantly, in an idealized left ventricle example, we show that the coupled model yields physiological pressure-volume loops and naturally recapitulates the isovolumic contraction and relaxation phases of the cardiac cycle without any additional numerical techniques. Furthermore, we provide a new derivation of the scheme inspired by the Approximate Newton Method of Chan (1985), explaining how the proposed numerical scheme combines the stability of monolithic approaches with the modularity and flexibility of partitioned approaches.

Optogenetics Sheds Light on Brown and Beige Adipocytes.

Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders. This review examines the therapeutic potential of brown and beige adipocytes for obesity and metabolic disorders, focusing on recent studies that employ optogenetics for thermogenesis control in these cells. The findings delve into the mechanisms underlying UCP1-dependent and UCP1-independent thermogenesis and how optogenetic approaches can be used to precisely modulate energy expenditure and induce thermogenesis. The convergence of adipocyte biology and optogenetics presents an exciting frontier in combating metabolic disorders and advancing our understanding of cellular regulation and energy balance.

Over the Hills and Through the Hollers: How One Program is Assisting Residents of Appalachian with Opioid Use Recovery.

Introduction: The consequences of increasing opioid misuse in the U.S. over the last two decades have been severe, contributing to hundreds of thousands of lives lost and heavy tolls on individuals, families, and society. The Appalachian Region has been hit particularly hard, with its predominantly rural landscape seeing disproportionate increases in opioid misuse and overdoses. These cases have been difficult to address due to poor treatment access and capacity constraints in many areas of Appalachia. Purpose: The current study focuses on evaluating The Kentucky Access to Recovery Program (KATR), which provides services to individuals recovering from opioid addiction residing in several counties in Eastern Kentucky. Its purpose is to understand the impact of KATR on service recipients' access to recovery services and supports. Methods: Semi-structured interviews were conducted with 12 service recipients, three service providers, and four vendors of support services related to housing, transportation, medical/dental care, employment, and childcare. Qualitative data were analyzed using thematic analysis. Results: Themes related to individual-level impacts were identified and discussed, including behavioral changes related to recovery, physical and mental health improvements, relationship repair, regaining custody of children, provision of needed supports, and ability to gain employment and improve finances. Study findings showed that KATR had meaningful impacts on the lives of service recipients by helping meet needs and reducing barriers to their ongoing recovery. Implications: Through its use of vouchers for support services and basic-needs provision, KATR demonstrates a potentially effective strategy for increasing access to health-related social services for persons in recovery in predominantly rural areas.

Complexities of protecting children from violence during the COVID-19 pandemic: Providers' and policymakers' best practices, innovations and challenges in 12 countries.

BACKGROUND: Globally, the COVID-19 pandemic has put children at an increased risk of neglect, violence and other human rights violations. Despite growing evidence of its impact on child protective services, there has been a dearth of research from low- and middle-income countries. OBJECTIVE: This cross-sectional qualitative study explored service providers' and policymakers' views and experiences of children's protection, in real-time, in the last quarter of 2020. METHODS: A smartphone app-based survey containing both open- and closed-ended questions was used. The data were analyzed using descriptive statistics and qualitative content analysis. PARTICIPANTS AND SETTING: Eighty-four respondents participated, including service providers, service managers and policymakers, mostly representing non-governmental organizations (NGOs), civil society organizations (CSOs) and governments across 12 countries (predominantly Kenya, South Africa and the Philippines). RESULTS: Most respondents reported their sectors had experienced challenges in protecting children from violence - particularly delays in reporting abuse and pursuing justice, and reaching those living in poor and/or rural areas. Good practices and innovations in children's protection during the pandemic were reported in several domains: advocacy and signposting; justice; health care; education and awareness-raising; children's visibility; and virtual service delivery. Community resources and involvement were also highlighted as vital. The ineffectiveness of child protection laws, policies and organizational responses, however, hindered the implementation of effective practices. CONCLUSIONS: The COVID-19 pandemic has accentuated the complexities and interconnectivity of systems, processes and actors and their joint impact on children's protection and rights. Collectively, the findings reinforce the criticality of collaborative, urgent and child-centered responses.

Non-prescribing clinicians' treatment orientations and attitudes toward treatments for opioid use disorder: Rural differences.

INTRODUCTION: The United States has experienced substantial increases in opioid use for more than two decades. This growth has impacted rural areas where overdoses have risen drastically during this time period and more often involve prescription opioids than in urban areas. Medications for opioid use disorders (MOUDs) are highly underutilized in rural settings due to lack of access, inadequate prescribing, and stigma. METHODS: The study collected data using a cross-sectional online survey of nonprescribing clinicians (NPCs) involved in the treatment of substance use disorders (SUDs) in the United States. The study used multiple recruitment methods to obtain a purposive sample of NPCs from a variety of geographical contexts across the nation. The survey assessed demographic and practice characteristics including rurality of practice location, exposure and training related to MOUDs, treatment orientation, treatment preferences for opioid use disorder (OUD), and attitudes toward MOUDs. The study compared treatment preferences for OUD and attitudes toward MOUDs based on rurality of practice location. We tested a mediation model to determine whether the relationship between rurality of practice setting and attitudes toward MOUDs is mediated by treatment orientation. RESULTS: Most of the 636 NPCs surveyed favored a combination of MOUDs and psychosocial treatment. Compared to clinicians practicing in suburban or urban areas, self-identified rural clinicians were more likely to favor MOUDs alone as most effective and less likely to endorse a combination of MOUDs and psychosocial treatment. Although most NPCs were supportive of MOUDs overall, many endorsed misconceptions related to MOUDs. Rural clinicians were less likely to perceive MOUDs as effective or acceptable compared to those in urban settings. Results of a mediation analysis indicated that practicing in a rural location compared to in an urban location directly and indirectly influenced attitudes toward MOUDs through an effect on treatment orientation. CONCLUSIONS: NPCs play important roles in the implementation of MOUDs, and while efforts to increase their knowledge of and exposure to MOUDs have contributed broadly to more favorable attitudes toward MOUDs among NPCs, this study's findings indicate that additional efforts are still needed, particularly among NPCs who work in rural settings. Findings also indicate that, among rural clinicians, increasing knowledge of and exposure to harm reduction principles may be a necessary prerequisite to engaging them in the implementation of specific harm reduction strategies such as MOUDs.

Testing Mechanisms of Change for Text Message-Delivered Cognitive Behavioral Therapy: Randomized Clinical Trial for Young Adult Depression.

BACKGROUND: Current psychiatric epidemiological evidence estimates that 17% of young adults (aged 18-25 years) experienced a major depressive episode in 2020, relative to 8.4% of all adults aged ≥26 years. Young adults with a major depressive episode in the past year are the least likely to receive treatment for depression compared with other age groups. OBJECTIVE: We conducted a randomized clinical trial following our initial 4-week SMS text message-delivered cognitive behavioral therapy (CBT-txt) for depression in young adults. We sought to test mechanisms of change for CBT-txt. METHODS: Based on participant feedback, outcome data, and the empirical literature, we increased the treatment dosage from 4-8 weeks and tested 3 mechanisms of change with 103 young adults in the United States. Participants were from 34 states, recruited from Facebook and Instagram and presenting with at least moderate depressive symptomatology. Web-based assessments occurred at baseline prior to randomization and at 1, 2, and 3 months after enrollment. The primary outcome, the severity of depressive symptoms, was assessed using the Beck Depression Inventory II. Behavioral activation, perseverative thinking, and cognitive distortions were measured as mechanisms of change. Participants were randomized to CBT-txt or a waitlist control condition. Those assigned to the CBT-txt intervention condition received 474 fully automated SMS text messages, delivered every other day over a 64-day period and averaging 14.8 (SD 2.4) SMS text messages per treatment day. Intervention texts are delivered via TextIt, a web-based automated SMS text messaging platform. RESULTS: Across all 3 months of the study, participants in the CBT-txt group showed significantly larger decreases in depressive symptoms than those in the control group (P<.001 at each follow-up), producing a medium-to-large effect size (Cohen d=0.76). Over half (25/47, 53%) of the treatment group moved into the "high-end functioning" category, representing no or minimal clinically significant depressive symptoms, compared with 15% (8/53) of the control condition. Mediation analysis showed that CBT-txt appeared to lead to greater increases in behavioral activation and greater decreases in cognitive distortions and perseverative thinking across the 3-month follow-up period, which were then associated with larger baseline to 3-month decreases in depression. The size of the indirect effects was substantial: 57%, 41%, and 50% of the CBT-txt effect on changes in depression were mediated by changes in behavioral activation, cognitive distortions, and perseverative thinking, respectively. Models including all 3 mediators simultaneously showed that 63% of the CBT-txt effect was mediated by the combined indirect effects. CONCLUSIONS: Results provide evidence for the efficacy of CBT-txt to reduce young adult depressive symptoms through hypothesized mechanisms. To the best of our knowledge, CBT-txt is unique in its SMS text message-delivered modality, the strong clinical evidence supporting efficacy and mechanisms of change. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551702; https://clinicaltrials.gov/study/NCT05551702.

Deep Learning for Localized Detection of Optic Disc Hemorrhages.

PURPOSE: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs. DESIGN: Development and testing of a deep learning algorithm. METHODS: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage. The images were split into training (n = 1340), validation (n = 167), and test (n = 165) datasets. Two state-of-the-art deep learning algorithms based on either object-level detection or image-level classification were trained on the dataset. These models were compared to one another and against 2 independent glaucoma specialists. We evaluated model performance by the area under the receiver operating characteristic curve (AUC). AUCs were compared with the Hanley-McNeil method. RESULTS: The object detection model achieved an AUC of 0.936 (95% CI = 0.857-0.964) across all held-out images (n = 165 photographs), which was significantly superior to the image classification model (AUC = 0.845, 95% CI = 0.740-0.912; P = .006). At an operating point selected for high specificity, the model achieved a specificity of 94.3% and a sensitivity of 70.0%, which was statistically indistinguishable from an expert clinician (P = .7). At an operating point selected for high sensitivity, the model achieves a sensitivity of 96.7% and a specificity of 73.3%. CONCLUSIONS: An autonomous object detection model is superior to an image classification model for detecting disc hemorrhages, and performed comparably to 2 clinicians.

Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes.

Brown adipocytes are unique in that they expend energy and produce heat to maintain euthermia through expression of uncoupling protein-1 (UCP1). Given their propensity to stimulate weight loss and promote resistance to obesity, they are a compelling interventional target for obesity-related disorders. Here, we tested whether an optogenetic approach could be used to activate UCP1-dependent thermogenesis in brown adipocytes. We generated brown adipocytes expressing a bacterial-derived photoactivatable adenylyl cyclase (bPAC) that, upon blue light stimulation, increases UCP1 expression, fuel uptake and thermogenesis. This unique system allows for precise, chemical free, temporal control of UCP1-dependent thermogenesis, which can aid in our understanding of brown adipocyte biology and development of therapies that target obesity-related disorders.

Inhibitors of Rho kinases (ROCK) induce multiple mitotic defects and synthetic lethality in BRCA2-deficient cells.

The trapping of Poly-ADP-ribose polymerase (PARP) on DNA caused by PARP inhibitors (PARPi) triggers acute DNA replication stress and synthetic lethality (SL) in BRCA2-deficient cells. Hence, DNA damage is accepted as a prerequisite for SL in BRCA2-deficient cells. In contrast, here we show that inhibiting ROCK in BRCA2-deficient cells triggers SL independently from acute replication stress. Such SL is preceded by polyploidy and binucleation resulting from cytokinesis failure. Such initial mitosis abnormalities are followed by other M phase defects, including anaphase bridges and abnormal mitotic figures associated with multipolar spindles, supernumerary centrosomes and multinucleation. SL was also triggered by inhibiting Citron Rho-interacting kinase, another enzyme that, similarly to ROCK, regulates cytokinesis. Together, these observations demonstrate that cytokinesis failure triggers mitotic abnormalities and SL in BRCA2-deficient cells. Furthermore, the prevention of mitotic entry by depletion of Early mitotic inhibitor 1 (EMI1) augmented the survival of BRCA2-deficient cells treated with ROCK inhibitors, thus reinforcing the association between M phase and cell death in BRCA2-deficient cells. This novel SL differs from the one triggered by PARPi and uncovers mitosis as an Achilles heel of BRCA2-deficient cells.