Electrical synapses mediate embryonic hyperactivity in a zebrafish model of Fragile X syndrome.

Although hyperactivity is associated with a wide variety of neurodevelopmental disorders, the early embryonic origins of locomotion have hindered investigation of pathogenesis of these debilitating behaviors. The earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Gap junction electrical synapses drive early spontaneous behavior in zebrafish, prior to the emergence of chemical neurotransmitter networks. We use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome (FXS) model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show altered sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 34/35. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. We also use functional imaging to examine motor neuron and interneuron activity in early embryogenesis, finding genetic disruption of electrical gap junctions uncouples activity between mnx1 + motor neurons and interneurons. Taken together, our work highlights the importance of electrical synapses in motor development and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initial formation of locomotive circuits.Significance Statement The origins of hyperactivity in neurodevelopmental disorders are difficult to pinpoint in vertebrate systems. Zebrafish locomotive circuits initiate in early embryogenesis, with defined motor neurons and interneurons driving the earliest locomotive movements. Using a genetic model of hyperactivity, we show that Fragile X syndrome model fmr1 mutant embryos display hyperexcitable behavior and express excess gap junction connexin proteins on motor circuit neurons. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. Taken together, this data suggests hyperactive behavior initiates in the earliest phases of neurodevelopment.

Breast Cancer Immunotherapy: A Clinical Review for the Plastic Surgeon.

Background: Immunotherapy has transformed breast cancer management. However, it can be challenging to remain familiar with the adverse events, contraindications, and perioperative recommendations for each agent. Methods: We used FDALabel to identify all Food and Drug Administration-approved immunotherapies indicated for the treatment of breast cancer. We extracted details regarding warnings and precautions, indications, and adverse events from each package insert. Results: We identified nine immunotherapies belonging to three classes: anti-human epidermal growth factor receptor 2 (HER2) agents, anti-programmed cell death protein 1 (PD-1) agents, and anti-trophoblast cell-surface antigen 2 (TROP-2) agents. Cardiotoxicity, including heart failure and cardiomyopathy, was common among those receiving anti-HER2 agents, and hypothyroidism was common among patients receiving the anti-PD-1 agent. The anti-TROP-2 agent was associated with diarrhea and neutropenia. Given the adverse event profile for each drug, we recommend preoperative evaluation components, including transthoracic echocardiography, liver function tests, and thyroid panels. We also indicate here which immunotherapies raise concern for venous thromboembolism, hematoma, and infection. Conclusions: Using data from clinical trials, we recommend a preoperative evaluation tailored to the immunotherapeutic regimen of individual patients.

Sensitivity, specificity, and discordance with self-report of nail sample testing for alcohol and cannabis.

BACKGROUND: Nails accumulate the alcohol metabolite, ethyl glucuronide (ETG), and the cannabis metabolite, carboxy- delta-9-THC over 3-6 months. Few studies have examined nail toxicology testing's sensitivity and specificity and the agreement between nail testing and self-reported alcohol and marijuana use. METHODS: In an ongoing clinical trial, 1101 veterans completed initial telephone questionnaires and were then asked to mail nail clippings for substance use analysis. We examined sensitivity and specificity of ETG and carboxy- delta-9-THC in nails compared to self-report of alcohol use patterns (the AUDIT-C) and substance-related harms (alcohol and THC subscales of the ASSIST). We then examined factors associated with discordance between nails and self-report. RESULTS: Almost two-thirds (707/1101) of respondents mailed in nail clippings. Those with returned nails were disproportionately married, white race, older, and less depressed. At a threshold of 8pg/mg, sensitivity was only.50 to detect risky alcohol use and.49 to detect alcohol-related issues. Sensitivity for marijuana issues was only.61. Specificity was greater than.77 for all measures. Factors associated with positive nails/negative self-report (i.e. false positives) for risky alcohol use on the Audit-C included more pain and being unmarried; false positive nails for alcohol-related issues on the ASSIST were associated with being unmarried and non-Hispanic ethnicity. False positive nails for THC-related issues on the ASSIST were associated with being African American, Hispanic, and having had legal issues. CONCLUSIONS: At standard cut-offs, nail measures had low sensitivity and higher specificity. The groups who disproportionately submit positive nails/negative self-report could have substance use patterns not adequately captured by self-report, inaccurate self-report due to social pressures, or distinct drug metabolism.

Rectus Abdominis Muscle Atrophy and Asymmetry After Pulmonary Lobectomy.

INTRODUCTION: Pulmonary lobectomy can result in intercostal nerve injury, leading to denervation of the rectus abdominis (RA) resulting in asymmetric muscle atrophy or an abdominal bulge. While there is a high rate of intercostal nerve injury during thoracic surgery, there are no studies that evaluate the magnitude and predisposing factors for RA atrophy in a large cohort. METHODS: A retrospective chart review was conducted of 357 patients who underwent open, thoracoscopic or robotic pulmonary lobectomy at a single academic center. RA volumes were measured on computed tomography scans preoperatively and postoperatively on both the operated and nonoperated sides from the level of the xiphoid process to the thoracolumbar junction. RA volume change and association of surgical/demographic characteristics was assessed. RESULTS: Median RA volume decreased bilaterally after operation, decreasing significantly more on the operated side (-19.5%) versus the nonoperated side (-6.6%) (P < 0.0001). 80.4% of the analyzed cohort experienced a 10% or greater decrease from preoperative RA volume on the operated side. Overweight individuals (body mass index 25.5-29.9) experienced a 1.7-fold greater volume loss on the operated side compared to normal weight individuals (body mass index 18.5-24.9) (P = 0.00016). In all right-sided lobectomies, lower lobe resection had the highest postoperative volume loss (Median (interquartile range): -28 (-35, -15)) (P = 0.082). CONCLUSIONS: This study of postlobectomy RA asymmetry includes the largest cohort to date; previous literature only includes case reports. Lobectomy operations result in asymmetric RA atrophy and predisposing factors include demographics and surgical approach. Clinical and quality of life outcomes of RA atrophy, along with mitigation strategies, must be assessed.

Investigating cognitive and motivational proximal outcomes in a randomized clinical trial of writing about the future self to reduce drinking.

BACKGROUND: Drinking identity (the extent to which one links the self with drinking alcohol) is a unique risk factor for college students' hazardous drinking that is not directly targeted by existing interventions. We conducted a study that aimed to decrease drinking identity among college students with hazardous drinking. We adapted a writing task about the future self and tested whether three writing sessions could decrease drinking identity and change drinking. We also investigated whether two additional factors (writing perspective and inclusion of participants' social networks) would enhance task impact. The present study evaluated whether posited proximal cognitive and motivational outcomes (drinking identity, self-efficacy, readiness to change, and drinking intentions) changed immediately after each writing session. METHOD: The study is a randomized clinical trial in which hypotheses and analyses were pre-registered. Participants were 328 college students who met hazardous drinking criteria. The study had a 2 (narrative writing topic: low-risk drinker vs. reduced smartphone use) × 2 (writing perspective: first-person vs. non-first-person) × 2 (social network instruction: instructed to include vs. not) factorial design. Proximal outcomes were drinking identity, self-efficacy, readiness to change, and drinking intentions. The clinical outcome was alcohol consumption. Participants completed three laboratory sessions at weekly intervals that included the writing task and pre- and post-task assessments. RESULTS: Results were largely null, except that readiness to reduce drinking was higher in the low-risk drinker condition and increased over the lab sessions. Time effects indicated that reductions in drinking identity, drinking intentions, and alcohol consumption, and increases in self-efficacy were observed but did not change above and beyond control conditions. CONCLUSIONS: Findings indicate the need to strengthen the writing task and select a more appropriate control task to target proposed proximal outcomes. Future studies might try personalizing the task, evaluating its efficacy with individuals motivated to change their drinking, and using a control task that does not involve imagining a future self.

Pharmacokinetics of long-acting cephapirin and cloxacillin after intramammary administration in dairy goats.

Determining the pharmacokinetics of intramammary antimicrobials in goats can assist in predicting appropriate meat and milk withdrawal intervals for drugs that are effective at treating subclinical mastitis due to non-aureus Staphylococci during the dry period. Twenty-four healthy, lactating does were enrolled in this study. Half were administered 300 mg of cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica, Duluth, GA) via intramammary infusion into each half of the udder. The remaining does had 500 mg cloxacillin benzathine (Orbenin DC, Merck & Co., Rahway, NJ) administered per half. Plasma was collected before treatment and for 7 days post-treatment followed by analysis via liquid chromatography with tandem mass spectroscopy. Pharmacokinetic parameters were determined using noncompartmental methods via commercial software (MonolixSuite). The mean maximum concentration (Cmax) of cephapirin of 0.073 µg/mL was noted at 7.06 h post-administration (Tmax). The area under the plasma concentration curve based on the final sampling point (AUClast) was 1.06 h × µg/mL. The mean residence time until the final sampling point (MRTlast) was 13.55 h. Mean terminal half-life (T½) of cephapirin was 6.98 h. In CLOX does, Cmax was 0.074 µg/mL with a Tmax of 18 h, AUClast was 5.71 h × µg/mL, T½ was 77.45 h, and MRTlast was 65.36 h. Despite both products being formulated with benzathine salts, marked differences were noted in pharmacokinetic parameters including AUC, T1/2, and MRTlast. This data will be used to plan sampling schedules for milk and tissue residue depletion studies for both products.

Women Who Experience More Affectionate Touch Report Better Body Satisfaction and Relationship Outcomes.

Affectionate touch (e.g. hugging, handholding) is an essential component of many intimate relationships and is a primary contributor to overall relationship satisfaction as well as sexual satisfaction. Affectionate touch is understood to be a form of non-verbal communication in which the giver is expressing positive feelings toward the receiver. Here, we propose that affectionate touch also positively impacts receivers' body satisfaction, because affectionate touch is a positive message communicated toward the receiver's body. In a cross-sectional sample of romantically partnered women (N = 1,156), we assessed the association between affectionate touch frequency and body satisfaction. We also investigated whether affectionate touch is associated with relationship/sexual satisfaction in part because touch helps to improve women's evaluations of their own bodies. Our results showed that body satisfaction was a significant, partial mediator and a valid path through which affectionate touch shapes relationship quality. Receiving affectionate touch could bolster relationship satisfaction and self-perceptions among women. Given the prevalence of body dissatisfaction amongst women, these results suggest that the underexplored associations between affectionate touch and body satisfaction may have significant impacts on a wide array of future empirical and applied research trajectories.

The Impacts of Lifetime Violence on Women's Current Sexual Health.

Background: Intimate partner violence (IPV), nonpartner sexual violence (SV), child sexual and physical abuse, and neglect have detrimental impacts on women's reproductive and sexual health. More empirical studies are needed to investigate the negative impacts of lifetime violence, including physical or sexual child abuse, nonpartner SV, physical, sexual, and psychological IPV on women's sexual health to better understand long-term impacts from IPV and physical or sexual child abuse. Materials and Methods: We used data from Wellness, Health and You, an ongoing health registry. A total of 1,213 women were included in data analysis. Our aim was to investigate the associations between lifetime IPV, nonpartner SV, child abuse, and women's current sexual health defined using Patient-Reported Outcomes Measurement Information System (PROMIS) measures of sexual health (e.g., sexual satisfaction, interest, and functioning), sexual assertiveness, female sexual subjectivity, and use of online resources to address sexual needs. Multivariate analysis of covariance was used to investigate demographic factors (e.g., age and current relationship) as potential correlates of current sexual health. Results: Women with lifetime experiences of physical, sexual, or psychological IPV, nonpartner SV, and child physical or sexual abuse reported lower sexual satisfaction compared to women with no history of lifetime violence (p < 0.0001). However, lifetime violence was not correlated with sexual interest, sexual functioning, sexual subjectivity, nor sexual assertiveness. Conclusion: Lifetime experiences of violence (i.e., IPV, nonpartner SV, child abuse) are associated with poorer sexual health. Asking questions about past sexual and physical violence/abuse in ways that support disclosure is important toward improving women's physical and sexual health and wellbeing.

Erectile dysfunction prevalence in the United States: report from the 2021 National Survey of Sexual Wellbeing.

BACKGROUND: There has been a great deal of public speculation regarding a surge in erectile dysfunction (ED) in younger men despite data consistently indicating that the ED prevalence rates increase with age. AIM: In this study we sought to assess the prevalence and risk of experiencing ED in a nationally representative sample of men in the United States across various social groups, describe comorbidities, and examine barriers to treatment. METHODS: Data from the 2021 National Survey of Sexual Wellbeing were analyzed by utilizing the Ipsos KnowledgePanel®, a probability-based online panel, for the purpose of obtaining US nationally representative data of adults aged 18 years and older. The analytic sample consisted of 1822 cisgender men ranging in age from 18 to 87 years, with a mean age of 47.5 years. OUTCOMES: Study outcomes were ED as measured by the 5-item version of the International Index of Erectile Function (IIEF-5), as well as self-reported diagnosis by a medical professional, comorbidities with other health issues, medications taken for ED, and barriers to treatment. RESULTS: The ED prevalence rate based on IIEF-5 scores was 24.2%. Prevalence increased with age: 52.2% of the 75+ age group, and 48.0% of the 65-74 age group meeting diagnostic criteria for ED. Diagnostic criteria were met for more participants in the 18-24 age group (17.9%) than the 25-34 (13.3%) or 35-44 (12.7%) age groups, but less than the 45-54 (25.3%) or 55-64 (33.9%) age groups. Only 7.7% (n = 141) of the sample reported having been diagnosed by a provider (n = 4 in 25-34, n = 6 in 35-44, n = 13 in 45-54, n = 39 in 55-64, n = 44 in 65-74, and n = 34 in ≥75-year olds), indicating a gap in access to treatment. The most common reason selected for not accessing care for ED concerns was a lack of need to see a provider in the past year. CLINICAL IMPLICATIONS: The discrepancy between ED self-report and medical diagnosis is critical, given that ED can be an indication of underlying health risks. STRENGTHS AND LIMITATIONS: This study is the first nationally representative update to information regarding the prevalence of ED in almost 2 decades. Standard administration of the IIEF-5 is limited to participants who have had sex in the last 6 months, so these rates do not include those men with ED who have been avoiding penetrative sex for a significant time. CONCLUSION: The results indicate that ED prevalence and severity remain highest in older age groups and that most individuals who meet criteria for ED have not sought medical care related to this concern.

Diversity in online resources for breast reconstruction: What do patients see?

BACKGROUND: Online resources are commonly used by patients to obtain information on breast reconstruction. Despite the key role of these resources in patient decision-making, their visual content has not yet been evaluated. This study sought to 1) characterize the presence and content of visual aids in online patient education breast reconstruction resources and 2) determine if the women represented in these visual aids reflect the breast reconstruction patient population in the United States. METHODS: The top 10 Google websites and the first 400 Google Images containing photographs/graphics depicting human skin for the search phrase "breast reconstruction" were analyzed. Images were categorized by content as "Before/After," "Surgical/Anatomical," "Step-by-Step," or "Breast-Centric Stock Images." Image subjects were classified by skin tone into "White" or "Non-White" using the Fitzpatrick scale and by body type into "Lean" or "Full-Figured." RESULTS: In total, 471 images were analyzed. These were predominantly "Before/After" images (43.9%), followed by "Breast-Centric Stock Images" (27.4%), "Surgical/Anatomical" (24.2%), and "Step-by-Step" (4.5%). The majority of all images depicted "White" skin types (90.7%) and "Lean" body types (73.0%). "Before/After" images were more likely to show "Full-Figured" women than the other content categories (p < 0.0001) and had the highest percentage of "Non-White" skin types (35.3%). CONCLUSIONS: Our findings demonstrate that breast reconstruction online resources are not reflective of the patient population seeking reconstruction. Improving the diversity of online image resources can both better represent our diverse patient population as well as better align patient expectations with postoperative outcomes, likely improving patient satisfaction.

Accelerated Aging and Microsatellite Instability in Recessive Dystrophic Epidermolysis Bullosa-Associated Cutaneous Squamous Cell Carcinoma.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severely debilitating disorder caused by pathogenic variants in COL7A1 and is characterized by extreme skin fragility, chronic inflammation, and fibrosis. A majority of patients with RDEB develop squamous cell carcinoma, a highly aggressive skin cancer with limited treatment options currently available. In this study, we utilized an approach leveraging whole-genome sequencing and RNA sequencing across 3 different tissues in a single patient with RDEB to gain insight into possible mechanisms of RDEB-associated squamous cell carcinoma progression and to identify potential therapeutic options. As a result, we identified PLK-1 as a possible candidate for targeted therapy and discovered microsatellite instability and accelerated aging as factors potentially contributing to the aggressive nature and early onset of RDEB squamous cell carcinoma. By integrating multitissue genomic and transcriptomic analyses in a single patient, we demonstrate the promise of bridging the gap between genomic research and clinical applications for developing tailored therapies for patients with rare genetic disorders such as RDEB.

Evaluating distress as a moderator of the relationship between drinking identity and hazardous drinking during the post-college transition.

Drinking identity (the extent to which one associates the self with drinking alcohol) is a robust predictor of young adult hazardous drinking (HD; heavy drinking and alcohol-related problems), and decreases in drinking identity have been linked to the decline in HD that often occurs following college graduation. Identifying moderators is key to recognizing who is most at risk for continued HD given a drinking identity vulnerability. Using data from a longitudinal study of graduating college students from the U.S., we evaluated distress (depression, anxiety, stress symptoms) as a potential moderator. Between- and within-person components of drinking identity and distress were evaluated to consider both individual differences and variations within a person across time and changing contexts. Study hypotheses and data analysis plan were preregistered. Graduating college students who met HD criteria (N = 422) completed implicit and explicit drinking identity measures (assessed using reaction time and self-report measures, respectively), distress symptom questionnaires, and self-reported alcohol consumption and problems at four-month intervals for 2.5 years. Results supported moderation at the between-person level for alcohol consumption, with higher levels of implicit drinking identity and distress linked to greater subsequent alcohol consumption. Only between-person main effects for (explicit) identity and distress were linked to more subsequent alcohol-related problems. Though moderation findings were mixed, having a stronger drinking identity and/or greater distress was linked to continued HD risk in this sample. Individuals with these risk factors may benefit from enhanced prevention efforts to help graduates transition out of HD post-college.

Seeing is believing: The effect of subtle communication in social media on viewers' beliefs about depression and anxiety symptom trajectories.

OBJECTIVE: One barrier to treatment seeking, uptake, and engagement is the belief that nothing can be done to reduce symptoms. Given the widespread use of social media to disseminate information about important issues, including psychological health, we sought to understand how the influence of social media communication regarding mental health impacts viewers' beliefs about psychopathology recovery. METHOD: Undergraduate participants from a large Midwestern university (N = 322) were randomized to view a series of Tweets characterizing psychopathology from a fixed mindset perspective, a growth mindset perspective, or, in the control condition, Tweets unrelated to psychopathology. Afterward, they completed a series of questionnaires designed to assess beliefs about recovery from depression and anxiety. RESULTS: Participants in the growth mindset condition endorsed less pessimistic beliefs about their ability (i.e., self-efficacy) to alleviate symptoms of depression and anxiety, and they believed these symptoms to be less stable and innate relative to those in the fixed mindset condition. CONCLUSION: Social media communication that characterizes psychopathology from a growth mindset perspective may be a viable intervention for improving beliefs around mental health self-efficacy and the malleable nature of mental illness, particularly depression and anxiety. Clinicians may be able to use social media platforms to promote functional beliefs around mental illness.

Relationships Between Prenatal Cocaine Exposure, Cannabis-Use Onset and Emotional and Related Characteristics in Young/Emerging Adults.

Background: Exposure to substances in utero may have significant early-life consequences. Less is known about the effects in emerging adulthood, particularly regarding patterns of substance use and related characteristics.Objectives: In this study, we recruited emerging adults, followed since birth, who had been prenatally exposed, or not, to cocaine. Individuals reported on their cannabis, alcohol, and tobacco use, and measures of impulsivity, anhedonia, emotional regulation, and mental health were obtained. Comparisons were made between emerging adults with prenatal cocaine exposure and those without. Correlations were performed between psychological measures and substance use, and regression analyses were conducted to determine potential pathways by which such measures may relate to prenatal exposure or substance use.Results: Individuals with prenatal cocaine exposure (vs. those without) used cannabis at younger ages, reported greater cannabis-use severity, and demonstrated higher impulsivity, state anxiety, and alexithymia. Earlier age of onset of cannabis use was associated with higher impulsivity, state anxiety, alexithymia, and social and physical anhedonia. Cannabis-use age-of-onset mediated the relationship between prenatal cocaine-exposure status and state anxiety and between prenatal cocaine-exposure status and cannabis-use severity in emerging adulthood but not relationships between prenatal cocaine-exposure status and impulsivity or alexithymia in emerging adulthood. Findings suggest that adults with prenatal cocaine exposure may use cannabis at younger ages, which may relate to increased anxiety and more severe use.Conclusions: These findings suggest both mechanisms and possible intervention targets to improve mental health in emerging adults with prenatal cocaine exposure.

Writing about the future self to shift drinking identity: An experimental investigation.

College student drinking is prevalent and costly to public and personal health, leading to calls to identify and target novel mechanisms of behavior change. We aimed to manipulate drinking identity (a cognitive risk factor for hazardous drinking) via three sessions of narrative writing about a future self. We tested whether writing could shift drinking identity and would be accompanied by changes in alcohol consumption and problems. Participants were college students meeting hazardous drinking criteria (N = 328; Mage = 20.15; 59% women, 40% men, 1% gender-diverse; 60% white; 23% Asian; 12% multiple races; 2% other racial groups; 8% identified as Hispanic/Latino/a/x). The study had a 2 [narrative writing topic: low-risk drinker vs. reduced smartphone use] × 2 [writing perspective: first person vs. non-first-person] × 2 [social network instruction: instructed to include vs. not] factorial design. Outcomes were drinking identity, drinking refusal self-efficacy, alcohol consumption, alcohol-related problems, and craving. Participants completed three writing sessions and online follow-up assessments at 2, 4, and 12 weeks. The study is a registered clinical trial; hypotheses and analyses were preregistered (https://osf.io/vy2ep/). Contrary to predictions, narrative writing about a future self as a low-risk drinker did not significantly impact outcomes. Null results extended to expected interactions with writing perspective and social network instructions. The narrative writing task did not shift drinking or alcohol-related outcomes. Future experimental work may benefit from greater flexibility in conceptualizing a future self, recruiting individuals interested in behavior change, and more sensitive measures of drinking identity.

Subscales of alexithymia show unique pathways through reappraisal and suppression to anxiety, depression and stress.

The goal of this work was to explore associations of constituent factors of alexithymia on mental health and potential mediating effects of emotion regulation strategies, specifically suppression and reappraisal. Data were collected through the crowd-sourcing platform Amazon Mechanical Turk (MTURK). Three hundred seventy-seven individuals completed questionnaires related to distress (Depression Anxiety Stress Scales [DASS]), emotion regulation (Emotion Regulation Questionnaire [ERQ]) and Alexithymia (Bermond-Vorst Alexithymia Questionnaire [BVAQ]). Three mediation models were constructed for depression, anxiety and stress, with BVAQ subscales (verbalizing, identifying, emotionalizing, fantasizing, and analyzing) as predictors and ERQ subscales (suppression and reappraisal) as mediators. Results indicated 37.3 % variance in depression, 25.2 % variance in anxiety, and 35.3 % variance in stress was explained by each model. Direct associations revealed emotionalizing and fantasizing were negatively associated with depression, anxiety, and stress, while verbalizing was additionally associated with depression, identifying was additionally associated with anxiety, and all four BVAQ subscales were associated with stress. BVAQ subscales demonstrated negative associations with reappraisal and positive associations with suppression that mediated anxiety and depression. However, suppression did not mediate relationships between BVAQ subscales with stress. Findings support the importance of examining multiple factors of alexithymia and associations with emotion regulation strategies and distress.

Mechanical Intercellular Communication via Matrix-Borne Cell Force Transmission During Vascular Network Formation.

Intercellular communication is critical to the formation and homeostatic function of all tissues. Previous work has shown that cells can communicate mechanically via the transmission of cell-generated forces through their surrounding extracellular matrix, but this process is not well understood. Here, mechanically defined, synthetic electrospun fibrous matrices are utilized in conjunction with a microfabrication-based cell patterning approach to examine mechanical intercellular communication (MIC) between endothelial cells (ECs) during their assembly into interconnected multicellular networks. It is found that cell force-mediated matrix displacements in deformable fibrous matrices underly directional extension and migration of neighboring ECs toward each other prior to the formation of stable cell-cell connections enriched with vascular endothelial cadherin (VE-cadherin). A critical role is also identified for calcium signaling mediated by focal adhesion kinase and mechanosensitive ion channels in MIC that extends to multicellular assembly of 3D vessel-like networks when ECs are embedded within fibrin hydrogels. These results illustrate a role for cell-generated forces and ECM mechanical properties in multicellular assembly of capillary-like EC networks and motivates the design of biomaterials that promote MIC for vascular tissue engineering.