Virtual AppLication-supported Environment To INcrease Exercise (VALENTINE) during cardiac rehabilitation study: Rationale and design.

BACKGROUND: In-person, exercise-based cardiac rehabilitation improves physical activity and reduces morbidity and mortality for patients with cardiovascular disease. However, activity levels may not be optimized and decline over time after patients graduate from cardiac rehabilitation. Scalable interventions through mobile health (mHealth) technologies have the potential to augment activity levels and extend the benefits of cardiac rehabilitation. METHODS: The VALENTINE Study is a prospective, randomized-controlled, remotely-administered trial designed to evaluate an mHealth intervention to supplement cardiac rehabilitation for low- and moderate-risk patients (ClinicalTrials.gov NCT04587882). Participants are randomized to the control or intervention arms of the study. Both groups receive a compatible smartwatch (Fitbit Versa 2 or Apple Watch 4) and usual care. Participants in the intervention arm of the study additionally receive a just-in-time adaptive intervention (JITAI) delivered as contextually tailored notifications promoting low-level physical activity and exercise throughout the day. In addition, they have access to activity tracking and goal setting through the mobile study application and receive weekly activity summaries via email. The primary outcome is change in 6-minute walk distance at 6-months and, secondarily, change in average daily step count. Exploratory analyses will examine the impact of notifications on immediate short-term smartwatch-measured step counts and exercise minutes. CONCLUSIONS: The VALENTINE study leverages innovative techniques in behavioral and cardiovascular disease research and will make a significant contribution to our understanding of how to support patients using mHealth technologies to promote and sustain physical activity.

Accuracy of a Smartphone-based Autorefractor Compared with Criterion-standard Refraction.

SIGNIFICANCE: Uncorrected refractive error is a prevalent problem throughout the world especially among the low-income population who have limited access to professional eye care and cannot afford eyeglasses. PURPOSE: The purpose of this study was to evaluate the accuracy and usability of a low-cost, portable, smartphone-based autorefractor (Netra, EyeNetra Inc., Somerville, MA) in adults. METHODS: A cross-sectional study was conducted to compare the portable refractor with subjective (manifest and cycloplegic) refraction for sequential adult participants with best-corrected visual acuity of 20/40 or greater. For each method of refraction, the spherical equivalent was calculated. Differences between methods were tested with linear mixed regression models. A validated usability questionnaire was administered regarding ease of use (100-point scale, higher scores better) for the portable autorefractor. RESULTS: Eighty-seven subjects (152 eyes) were studied (age range, 20 to 90 years; mean ± standard deviation, 51.9 ± 18.3 years). Mean spherical equivalent by the portable device was -2.76 D (range, -14.75 to 3.63 D) compared with -2.49 D (range, -15.25 to 4.25 D) by manifest refraction. The mean relative difference in spherical equivalent between methods was -0.27 D (P = .001, significantly different than 0 D). The mean absolute difference between methods was 0.69 D (P < .001, significantly different than 0.5-D absolute difference). Similar results were found when comparing spherical equivalent between Netra and cycloplegic refraction methods. Subjects reported average ease of use for the Netra of 75.4 ± 19.8. CONCLUSIONS: The portable autorefractor had small but clinically significant differences from subjective refraction. The device's scores on the usability scale indicate good overall patient acceptance. The device may be valuable for use where there is limited access to a trained refractionist.

Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice.

Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies. Here, we describe the isolation and characterization of monoclonal brain-reactive antibodies from blood of women with brain-reactive serology and a child with ASD. We further demonstrate that male but not female mice exposed in utero to the C6 monoclonal antibody, binding to contactin-associated protein-like 2 (Caspr2), display abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as impairments in sociability, flexible learning and repetitive behavior. Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a child with ASD. Together these studies provide a methodology for obtaining monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can result from in utero exposure to maternal brain-reactive antibodies of single specificity and point toward the exciting possibility of prognostic and protective strategies.

Refractive error in underserved adults: causes and potential solutions.

PURPOSE OF REVIEW: To evaluate the epidemiology of uncorrected refractive errors (URE) in adults both in the United States and globally, health outcomes impacted by URE, common barriers to treatment, and propose potential interventions. RECENT FNDINGS: URE is the main cause of visual impairment and the second leading cause of blindness globally. Rates of URE are rising, and cause disability that reduces productivity, economic earnings, and the quality of life of affected individuals. Economic barriers, healthcare access, and sociocultural constraints are among the most fundamental barriers to correcting URE. However, innovative approaches are poised to lower rates of URE. SUMMARY: URE is a leading cause of preventable visual impairment with serious health consequences. Numerous social and financial barriers are associated with the high prevalence of URE in low-income adults. Novel delivery programs for eyeglasses and programs to provide refractive surgery to correct refractive error could decrease rates of URE.

A Physical Activity and Diet Just-in-Time Adaptive Intervention to Reduce Blood Pressure: The myBPmyLife Study Rationale and Design.

BACKGROUND: Smartphone applications and wearable devices are promising mobile health interventions for hypertension self-management. However, most mobile health interventions fail to use contextual data, potentially diminishing their impact. The myBPmyLife Study is a just-in-time adaptive intervention designed to promote personalized self-management for patients with hypertension. METHODS AND RESULTS: The study is a 6-month prospective, randomized-controlled, remotely administered trial. Participants were recruited from the University of Michigan Health in Ann Arbor, Michigan or the Hamilton Community Health Network, a federally qualified health center network in Flint, Michigan. Participants were randomized to a mobile application with a just-in-time adaptive intervention promoting physical activity and lower-sodium food choices as well as weekly goal setting or usual care. The mobile study application encourages goal attainment through a central visualization displaying participants' progress toward their goals for physical activity and lower-sodium food choices. Participants in both groups are followed for up for 6 months with a primary end point of change in systolic blood pressure. Exploratory analyses will examine the impact of notifications on step count and self-reported lower-sodium food choices. The study launched on December 9, 2021, with 484 participants enrolled as of March 31, 2023. Enrollment of participants was completed on July 3, 2023. After 6 months of follow-up, it is expected that results will be available in the spring of 2024. CONCLUSIONS: The myBPmyLife study is an innovative mobile health trial designed to evaluate the effects of a just-in-time adaptive intervention focused on improving physical activity and dietary sodium intake on blood pressure in diverse patients with hypertension. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05154929.

Text Messages to Promote Physical Activity in Patients With Cardiovascular Disease: A Micro-Randomized Trial of a Just-In-Time Adaptive Intervention.

BACKGROUND: Text messages may enhance physical activity levels in patients with cardiovascular disease, including those enrolled in cardiac rehabilitation. However, the independent and long-term effects of text messages remain uncertain. METHODS: The VALENTINE study (Virtual Application-supported Environment to Increase Exercise) was a micro-randomized trial that delivered text messages through a smartwatch (Apple Watch or Fitbit Versa) to participants initiating cardiac rehabilitation. Participants were randomized 4× per day over 6-months to receive no text message or a message encouraging low-level physical activity. Text messages were tailored on contextual factors (eg, weather). Our primary outcome was step count 60 minutes following a text message, and we used a centered and weighted least squares mean method to estimate causal effects. Given potential measurement differences between devices determined a priori, data were assessed separately for Apple Watch and Fitbit Versa users over 3 time periods corresponding to the initiation (0-30 days), maintenance (31-120 days), and completion (121-182 days) of cardiac rehabilitation. RESULTS: One hundred eight participants were included with 70 552 randomizations over 6 months; mean age was 59.5 (SD, 10.7) years with 36 (32.4%) female and 68 (63.0%) Apple Watch participants. For Apple Watch participants, text messages led to a trend in increased step count by 10% in the 60-minutes following a message during days 1 to 30 (95% CI, -1% to +20%), with no effect from days 31 to 120 (+1% [95% CI, -4% to +5%]), and a significant 6% increase during days 121 to 182 (95% CI, +0% to +11%). For Fitbit users, text messages significantly increased step count by 17% (95% CI, +7% to +28%) in the 60-minutes following a message in the first 30 days of the study with no effect subsequently. CONCLUSIONS: In patients undergoing cardiac rehabilitation, contextually tailored text messages may increase physical activity, but this effect varies over time and by device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

A randomized trial of a mobile health intervention to augment cardiac rehabilitation.

Mobile health (mHealth) interventions may enhance positive health behaviors, but randomized trials evaluating their efficacy are uncommon. Our goal was to determine if a mHealth intervention augmented and extended benefits of center-based cardiac rehabilitation (CR) for physical activity levels at 6-months. We delivered a randomized clinical trial to low and moderate risk patients with a compatible smartphone enrolled in CR at two health systems. All participants received a compatible smartwatch and usual CR care. Intervention participants received a mHealth intervention that included a just-in-time-adaptive intervention (JITAI) as text messages. The primary outcome was change in remote 6-minute walk distance at 6-months stratified by device type. Here we report the results for 220 participants enrolled in the study (mean [SD]: age 59.6 [10.6] years; 67 [30.5%] women). For our primary outcome at 6 months, there is no significant difference in the change in 6 min walk distance across smartwatch types (Intervention versus control: +31.1 meters Apple Watch, -7.4 meters Fitbit; p = 0.28). Secondary outcomes show no difference in mean step counts between the first and final weeks of the study, but a change in 6 min walk distance at 3 months for Fitbit users. Amongst patients enrolled in center-based CR, a mHealth intervention did not improve 6-month outcomes but suggested differences at 3 months in some users.

Integration of artificial vision with non-visual peripheral cues to guide mobility.

Visual prostheses can improve vision for people with severe vision loss, but low image resolution and lack of peripheral vision limit their effectiveness. To address both problems, we developed a prototype advanced video processing system with a headworn depth camera and feature detection capabilities. We used computer vision algorithms to detect landmarks representing a goal and plan a path towards the goal, while removing unnecessary distractors from the video. If the landmark fell outside the visual prosthesis's field-of-view (20 degrees central vision) but within the camera's field-of-view (70 degrees), we provided vibrational cues to the left or right temple to guide the user in pointing the camera. We evaluated an Argus II retinal prosthesis participant with significant vision loss who could not complete the task (finding a door in a large room) with either his remaining vision or his retinal prosthesis. His success rate improved to 57%, 37.5%, and 100% while requiring 52.3, 83.0, and 58.8 seconds to reach the door using only vibration feedback, retinal prosthesis with modified video, and retinal prosthesis with modified video and vibration feedback, respectively. This case study demonstrates a possible means of augmenting artificial vision. Clinical Relevance- Retinal prostheses can be enhanced by adding computer vision and non-visual cues.

Understanding Baseline Physical Activity in Cardiac Rehabilitation Enrollees Using Mobile Health Technologies.

BACKGROUND: Baseline physical activity in patients when they initiate cardiac rehabilitation is poorly understood. We used mobile health technology to understand baseline physical activity of patients initiating cardiac rehabilitation within a clinical trial to potentially inform personalized care. METHODS: The VALENTINE (Virtual Application-Supported Environment to Increase Exercise During Cardiac Rehabilitation Study) is a prospective, randomized-controlled, remotely administered trial designed to evaluate a mobile health intervention to supplement cardiac rehabilitation for low- and moderate-risk patients. All participants receive a smartwatch and usual care. Baseline physical activity was assessed remotely after enrollment and included (1) 6-minute walk distance, (2) daily step count, and (3) daily exercise minutes, both over 7 days and for compliant days, defined by >8 hours of watch wear time. Multivariable linear regression identified patient-level features associated with these 3 measures of baseline physical activity. RESULTS: From October 2020 to March 2022, 220 participants enrolled in the study. Participants are mostly White (184 [83.6%]); 67 (30.5%) are female and 84 (38.2%) are >65 years old. Most participants enrolled in cardiac rehabilitation after percutaneous coronary intervention (105 [47.7%]) or coronary artery bypass surgery (39 [17.7 %]). Clinical diagnoses include coronary artery disease (78.6%), heart failure (17.3%), and valve repair or replacement (26.4%). Baseline mean 6-minute walk distance was 489.6 (SD, 143.4) meters, daily step count was 6845 (SD, 3353), and exercise minutes was 37.5 (SD, 33.5). In a multivariable model, 6-minute walk distance was significantly associated with age and sex, but not cardiac rehabilitation indication. Sex but not age or cardiac rehabilitation indication was significantly associated with daily step count and exercise minutes. CONCLUSIONS: Baseline physical activity varies substantially in low- and moderate-risk patients enrolled in cardiac rehabilitation. Future studies are warranted to explore whether personalizing cardiac rehabilitation programs using mobile health technologies could optimize recovery. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04587882.

Robotic technology in ophthalmic surgery.

PURPOSE OF REVIEW: To provide an overview of the history, development, and potential applications of robotic technology, with a focus on ophthalmic surgery. An extensive literature review and authors' own perspectives were taken into account in selecting the most relevant articles from MEDLINE and Google scholar. RECENT FINDINGS: Most surgical specialties have introduced robots in current use. Although the application of robots in ophthalmic surgery is in its infancy today, its advantages and great potential is quite apparent. As robotics transcends utility and attain wider consensus among the surgical profession, ophthalmologists must acquaint themselves with this novel interdisciplinary field and its relevance to their specialty. SUMMARY: Future possibilities, including the prospects for nanotechnology in ophthalmology, are awaited.

Treatment viability of stem cells in ophthalmology.

PURPOSE OF REVIEW: Adult ocular stem cells have the potential to restore vision in patients previously deemed incurable. This review summarizes strides in stem cell research and stumbling blocks that must be overcome to enable treatment viability in ophthalmology. RECENT FINDINGS: Stem/progenitor cells located in different regions of the eye are capable of differentiating enabling cell repopulation and tissue regeneration. At present, limbal epithelial stem transplantation is the sole ocular cell-based therapy being implemented into clinical practice. Research performed in animal models gives hope for using similar strategies to treat a wide range of ocular diseases in humans. The essential step toward successful therapeutic exploitation is to unravel regulators that control their cell proliferation and renewal pathways. The recently identified very small embryonic-like stem cells (VSEL-SCs) present in the bone marrow could potentially be harvested for regeneration from cord blood via ex-vivo expansion and differentiation protocols SUMMARY: Although numerous impediments remain, the use of bioengineered stem cells is promising and may epitomize the future for replacement and regeneration of ocular tissues in various previously incurable ocular disorders.

Crosswalk Guidance System for the Blind.

Street crossing can be a significant challenge for visually impaired people, limiting their mobility especially in urban environments. To date, there are few solutions for this significant problem. Current approaches for guiding blind pedestrians in crosswalks have mainly focused on detection of crosswalks and crosswalk signals. Few studies have taken into consideration the mobility of a visually impaired person while street crossing. We programmed a commercially available, wearable goggle system to detect crosswalk signals, to plan a path across the street, and to provide verbal guiding cues with real-time semantic features to keep the user on the correct path. During verification testing, we found crosswalk signal detections were typically reliable but depended on hyper-parameters to reduce false positive errors in the crosswalk signs in a small number of cases. Testing with visually impaired subjects resulted in successful guidance at an outdoor crosswalk.

The effect of waveform asymmetry on perception with epiretinal prostheses.

Objective: Retinal prosthetic implants have helped improve vision in patients blinded by photoreceptor degeneration. Retinal implant users report improvements in light perception and performing visual tasks, but their ability to perceive shapes and letters is limited due to the low precision of retinal activation, which is exacerbated by axonal stimulation and high perceptual thresholds. A previous in vitro study in our lab used calcium imaging to measure the spatial activity of mouse retinal ganglion cells (RGCs) in response to electrical stimulation. Based on this study, symmetric anodic-first (SA) stimulation effectively avoided axonal activation and asymmetric anodic-first stimulation (AA) with duration ratios (ratio of the anodic to cathodic phase) greater than 10 reduced RGC activation thresholds significantly. Applying these novel stimulation strategies in clinic may increase perception precision and improve the overall patient outcomes. Approach: We combined human subject testing and computational modeling to further examine the effect of SA and AA stimuli on perception shapes and thresholds for epiretinal stimulation of RGCs. Main results: Threshold measurement in three Argus II participants indicated that AA stimulation could increase perception probabilities compared to a standard symmetric cathodic-first (SC) pulse, and this effect can be intensified by addition of an interphae gap (IPG). Our in silico RGC model predicts lower thresholds with AA and asymmetric cathodic-first (AC) stimuli compared to a SC pulse. This effect was more pronounced at shorter pulse widths. The most effective pulse for threshold reduction with short pulse durations (≤0.12 ms) was AA stimulation with small duration ratios (≤5) and long IPGs (≥2 ms). For the 0.5 ms pulse duration, SC stimulation with IPGs longer than 0.5 ms, or asymmetric stimuli with large duration ratios (≥20) were most effective in threshold reduction. Phosphene shape analysis did not reveal a significant change in percept elongation with SA stimulation. However, there was a significant increase in percept size (P < 0.01) with AA stimulation compared to the standard pulse in one participant. Significane: Including asymmetric waveform capability will provide more flexible options for optimization and personalized fitting of retinal implants.

Retinal vascular caliber and diabetes in a multiethnic Asian population.

OBJECTIVE: The aim of this study was to examine the relationship of retinal vascular caliber with diabetes and impaired fasting glucose (IFG) in a multiethnic Asian population. METHODS: This work was a population-based cross-sectional study comprising 3,404 Singaporean Chinese, Indian, and Malay participants. Retinal arteriolar and venular diameters, CRAE and CRVE, respectively were measured from digital retinal photographs. Diabetes was defined as physician-diagnosis of diabetes, self-reported use of diabetic medication, or fasting plasma glucose (FPG) > or = 7 mmol/L; IFG as FPG 6.1-6.9 mmol/L. RESULTS: After adjusting for age, gender, ethnicity, systolic blood pressure, body mass index, total cholesterol, triglycerides, smoking, and vascular caliber (Model 3), participants with diabetes had both larger CRAE and CRVE, compared to those with normal fasting glucose (NFG) or IFG. In a multivariate analysis, including clinical risk factors and CRVE, mean CRAE increased from 143.6 microm in NFG to 145.3 microm with diabetes (P for trend = 0.01). On the other hand, each mmol/L increase in FPG was associated with a 0.51-microm increase in CRVE (P=0.006). In a subgroup analysis stratified by ethnicity, the association between FPG and larger CRVE was predominantly present among ethnic Indians (0.9-microm increase in CRVE per mmol/L increase in FPG). CONCLUSION: Diabetes was associated with larger retinal arteriolar diameters and glucose level was associated with larger retinal venular diameters in this multiethnic Asian population. The magnitude of association between glucose level and venular widening was stronger among ethnic Indians.

Sub-Tenon's anaesthesia: a well tolerated and effective procedure for ophthalmic surgery.

PURPOSE OF REVIEW: To report recent advancements with sub-Tenon's anaesthesia for ocular surgery, accentuating the efficacy and safety of this technique. Further clinical implications are reviewed with regard to its technique, indications, benefits, and reported complications. RECENT FINDINGS: Sub-Tenon's anaesthesia, a versatile and technically easy procedure to master, has gained popularity with both ophthalmic surgeons and anaesthetists. This block is achieving repute as the block of choice, providing anaesthesia as well as akinesia during ophthalmic surgery. As the technique has further evolved and novel cannulae introduced, increasing complications have been documented. SUMMARY: Currently, there is no absolutely well tolerated orbital regional block technique. However, well founded evidence appears to support sub-Tenon's block as a safer option. Sound knowledge of orbital anatomy, pharmacology of anaesthetic agents, and prevention of potential complications are therefore crucial to perform sub-Tenon's block effectively and safely.

Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration.

PURPOSE OF REVIEW: To report the safety and efficacy of intravitreal injections for age-related macular degeneration (AMD). RECENT FINDINGS: Injecting antivascular endothelial growth factor drugs into the vitreal cavity brings new hope to many AMD patients. Currently, several antivascular endothelial growth factor drugs such as pegaptanib, ranibizumab, and bevacizumab are used via the intravitreal route for neovascular AMD. However, these injections are not without ocular or systemic complications. SUMMARY: Review of current literature suggests that intravitreal antivascular endothelial growth factor agents are generally a safe and effective treatment for neovascular AMD for up to 2-3 years. Presently, there is level I evidence to substantiate this conclusion for pegaptanib and ranibizumab, but not bevacizumab.

Readability of prescription labels and medication recall in a population of tertiary referral glaucoma patients.

PURPOSE: To evaluate readability of eye drop labels and accurate recall of prescription instructions in a glaucoma population. METHODS: A hospital-based, cross-sectional study. A trained, interviewer examined patient ability to read standard and larger font medication labels. A questionnaire was administered to ascertain accurate recall of prescribed eye drops. Clinical information was obtained through independent chart review. Glaucoma severity was classified according to a glaucoma staging system. The setting for the study was the glaucoma outpatient clinic, Royal Victorian Eye and Ear Hospital (Melbourne, Australia), a major tertiary referral centre. A total of 200 glaucoma patients (96.2% response), aged 45-90 years, on eye drops took part in the study. Non-English-speaking patients were excluded. The main outcome measure was the ability to read prescribed medication labels and accurately recall treatment regime was compared with glaucoma severity and the number of eye drops. RESULTS: Of the glaucoma patients, 12% were unable to read standard pharmacy labels. Only 5.5% were unable to read the larger font labels. Of the patients, 32% were not able to accurately recall the type of drops or prescribed frequency of instillation. An inability to read standard labels was associated with a threefold reduction in the likelihood of accurate medication recall (95% confidence intervals, 1.40-7.66, P < 0.05). Patients with three or more types of eye drops were five times less likely to recall their medications (95% confidence interval, 0.07-0.57, P < 0.05). CONCLUSIONS: Inability to read or recall prescribed eye drops was associated with glaucoma severity and the number of prescribed eye drops. These factors may impact significantly on patients' adherence to glaucoma medications.

Vitamin A nutrition among East Timor refugee children.

BACKGROUND AND OBJECTIVES: Children age 6 to 72 months, living in refugee camps are at increased risk of developing vitamin A deficiency (VAD), resulting in increased morbidity and mortality. Due to poverty, often this population group has limited access to foods containing vitamin A from animal-based food sources and do not commonly consume available foods containing beta-carotene. To date, there is a paucity of data on vitamin A intake in young refugee children. To determine vitamin A intake in children ages 6 to 72 months at refugee camps in East Timor. METHODS AND STUDY DESIGN: A cross sectional study was carried out among children ages 6 to 72 months at refugee camps near Dili, East Timor. A detailed vitamin A intake questionnaire was ascertained from the primary caretaker, and the criteria and indicator cut off values suggested by World Health Organization (WHO) were used to classify the populations' vitamin A risk. RESULTS: Although animal sources of vitamin A were limited due to costs, all 89 children commonly consumed fruit containing vitamin A sources more than 3 times a week. Most children (69.7%) had been breast fed regularly, while 30.3% combined with bottle milk. 80.9% of children received vitamin A supplementation. CONCLUSION: Children in East Timor refugee camps have adequate vitamin A intake.

Unilateral retinitis pigmentosa occurring in an individual with a mutation in the CLRN1 gene.

This case report depicts the clinical course of a female patient with unilateral retinitis pigmentosa, who first presented at the age of 12 years. Fundus photography at the time revealed unilateral pigmentary retinopathy, which was associated with extinguished electroretinogram (ERG) signal. At 35 years of age, fundus examination revealed deterioration of pre-existing unilateral pigmentary retinopathy with progressive visual field defect detected on Goldmann visual field testing. ERG findings remained unchanged and multifocal ERG showed unilateral decrease in amplitude in the affected eye. The patient was referred for genetic counselling. Next-generation sequencing identified a deleterious heterozygous c.118T>G (p.Cys40Gly) mutation in the CLRN1 gene.

Sex hormones and SLE: influencing the fate of autoreactive B cells.

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been conducted. While it is plausible that some sex-linked genes may contribute to the genetic predisposition for the disease, other likely culprits are the sex hormones estrogen and prolactin. In this chapter we review studies that have addressed the influence of sex hormones in SLE activity and discuss the recent data established in a BALB/c mouse transgenic for the heavy chain of an anti-DNA antibody. These mice are prone to develop lupus following exposure to exogenous sex hormones. We describe how estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence. Finally, we discuss the relevance and implications of these data for human disease.