ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways.

Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defenses. In exploring the finding that HCMV infection up-regulates tumor necrosis factor receptor 2 (TNFR2), a ligand for the pro-inflammatory antiviral cytokine TNFα, we found that the underlying mechanism was due to targeting of the protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 is the prototype 'sheddase', a family of proteases that cleaves other membrane-bound proteins to release biologically active ectodomains into the supernatant. HCMV impaired ADAM17 surface expression through the action of two virally-encoded proteins in its UL/b' region, UL148 and UL148D. Proteomic plasma membrane profiling of cells infected with an HCMV double-deletion mutant for UL148 and UL148D with restored ADAM17 expression, combined with ADAM17 functional blockade, showed that HCMV stabilized the surface expression of 114 proteins (P < 0.05) in an ADAM17-dependent fashion. These included reported substrates of ADAM17 with established immunological functions such as TNFR2 and jagged1, but also numerous unreported host and viral targets, such as nectin1, UL8, and UL144. Regulation of TNFα-induced cytokine responses and NK inhibition during HCMV infection were dependent on this impairment of ADAM17. We therefore identify a viral immunoregulatory mechanism in which targeting a single sheddase enables broad regulation of multiple critical surface receptors, revealing a paradigm for viral-encoded immunomodulation.

In vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome.

Cytomegaloviruses (CMVs) are highly adapted to their host species resulting in strict species specificity. Hence, in vivo examination of all aspects of CMV biology employs animal models using host-specific CMVs. Infection of rhesus macaques (RM) with rhesus CMV (RhCMV) has been established as a representative model for infection of humans with HCMV due to the close evolutionary relationships of both host and virus. However, the only available RhCMV clone that permits genetic modifications is based on the 68-1 strain which has been passaged in fibroblasts for decades resulting in multiple genomic changes due to tissue culture adaptations. As a result, 68-1 displays reduced viremia in RhCMV-naïve animals and limited shedding compared to non-clonal, low passage isolates. To overcome this limitation, we used sequence information from primary RhCMV isolates to construct a full-length (FL) RhCMV by repairing all mutations affecting open reading frames (ORFs) in the 68-1 bacterial artificial chromosome (BAC). Inoculation of adult, immunocompetent, RhCMV-naïve RM with the reconstituted virus resulted in significant viremia in the blood similar to primary isolates of RhCMV and furthermore led to high viral genome copy numbers in many tissues at day 14 post infection. In contrast, viral dissemination was greatly reduced upon deletion of genes also lacking in 68-1. Transcriptome analysis of infected tissues further revealed that chemokine-like genes deleted in 68-1 are among the most highly expressed viral transcripts both in vitro and in vivo consistent with an important immunomodulatory function of the respective proteins. We conclude that FL-RhCMV displays in vitro and in vivo characteristics of a wildtype virus while being amenable to genetic modifications through BAC recombineering techniques.

Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses.

CD58 is an adhesion molecule that is known to play a critical role in costimulation of effector cells and is intrinsic to immune synapse structure. Herein, we describe a virally encoded gene that inhibits CD58 surface expression. Human cytomegalovirus (HCMV) UL148 was necessary and sufficient to promote intracellular retention of CD58 during HCMV infection. Blocking studies with antagonistic anti-CD58 mAb and an HCMV UL148 deletion mutant (HCMV∆UL148) with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8+ HCMV-specific cytotoxic T lymphocytes (CTLs). Further, challenge of peripheral blood mononuclear cells ex vivo with HCMV∆UL148 increased both CTL and natural killer (NK) cell degranulation against HCMV-infected cells, including NK-driven antibody-dependent cellular cytotoxicity, showing that UL148 is a modulator of the function of multiple effector cell subsets. Our data stress the effect of HCMV immune evasion functions on shaping the immune response, highlighting the capacity for their potential use in modulating immunity during the development of anti-HCMV vaccines and HCMV-based vaccine vectors.

Downregulation of HLA-I by the molluscum contagiosum virus mc080 impacts NK-cell recognition and promotes CD8+ T-cell evasion.

Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of primary keratinocytes in the epidermis, MCV induces the proliferation of infected cells and this results in the production of wart-like growths. Full productive infection is observed only after the infected cells differentiate. During this prolonged replication cycle the virus must avoid elimination by the host immune system. We therefore sought to investigate the function of the two major histocompatibility complex class-I-related genes encoded by the MCV genes mc033 and mc080. Following insertion into a replication-deficient adenovirus vector, codon-optimized versions of mc033 and mc080 were expressed as endoglycosidase-sensitive glycoproteins that localized primarily in the endoplasmic reticulum. MC080, but not MC033, downregulated cell-surface expression of endogenous classical human leucocyte antigen (HLA) class I and non-classical HLA-E by a transporter associated with antigen processing (TAP)-independent mechanism. MC080 exhibited a capacity to inhibit or activate NK cells in autologous assays in a donor-specific manner. MC080 consistently inhibited antigen-specific T cells being activated by peptide-pulsed targets. We therefore propose that MC080 acts to promote evasion of HLA-I-restricted cytotoxic T cells.

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation.

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αß and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1-6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12-US21; a genetic arrangement, which is suggestive of an 'accordion' expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family.

No short-term savings in health care expenditures for physically active adults.

OBJECTIVE: The purpose of this study was to investigate the association of physical activity and health care expenditures in a nationally representative sample of non-disabled adults. METHODS: This was a secondary analysis of data from 8843 adults. Physical activity measures were derived from participants in the 2006 and 2007 National Health Interview Survey. Demographic and expenditure variables came from the Medical Expenditure Panel Survey data files for panels 12 (2007-2008) and 13 (2008-2009). Multivariable regression models were used to determine the association between levels of physical activity participation and total health care expenditures, drug expenditures, and out-of-pocket health care expenditures. RESULTS: Unadjusted data revealed lower health care expenditures among those whose activity level met the CDC guidelines with greater savings apparent among those who exercised above recommended guidelines. However, in the models that adjusted for age, sex, race, income and health status these differences disappeared. CONCLUSION: In the short-term, the amount of physical activity undertaken by an adult may have little effect on the expenditures for health services, drugs and the money expended directly out-of-pocket. However, given the benefits of physical activity in terms of chronic disease prevention there are very likely long-term expenditure savings to be had.

Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk.

Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3(R102G)), factor B (fB(R32Q)), and factor H (fH(V62I)) are associated with age-related macular degeneration (AMD) and other pathologies. Our published work showed that fB(R32Q) influences C3 convertase formation, whereas fH(V62I) affects factor I cofactor activity. Here we show how C3(R102G) (C3S/F) influences AP activity. In hemolysis assays, C3(102G) activated AP more efficiently (EC(50) C3(102G): 157 nM; C3(102R): 191 nM; P < 0.0001). fB binding kinetics and convertase stability were identical, but native and recombinant fH bound more strongly to C3b(102R) (K(D) C3b(102R): 1.0 µM; C3b(102G): 1.4 µM; P < 0.0001). Accelerated decay was unaltered, but fH cofactor activity was reduced for C3b(102G), favoring AP amplification. Combining disease "risk" variants (C3(102G), fB(32R), and fH(62V)) in add-back assays yielded sixfold higher hemolytic activity compared with "protective" variants (C3(102R), fB(32Q), and fH(62I); P < 0.0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease.

Enabling cross-country learning and exchange to support universal health coverage implementation.

As countries transition from external assistance while pursuing ambitious plans to achieve universal health coverage (UHC), there is increasing need to facilitate knowledge sharing and learning among them. Country-led and country-owned knowledge management is foundational to sustainable, more equitable external assistance for health and is a useful complement to more conventional capacity-building modalities provided under external assistance. In the context of external assistance, few initiatives use country-to-country sharing of practitioner experiences, and link learning to receiving guidance on how to adapt, apply and sustain policy changes. Dominant knowledge exchange processes are didactic, implicitly assuming static technical needs, and that practitioners in low- and middle-income countries require problem-specific, time-bound solutions. In reality, the technical challenges of achieving UHC and the group of policymakers involved continuously evolve. This paper aims to explore factors which are supportive of experience-based knowledge exchange between practitioners from diverse settings, drawing from the experience of the Joint Learning Network (JLN) for UHC-a global network of practitioners and policymakers sharing experiences about common challenges to develop and implement knowledge products supporting reforms for UHC-as an illustration of a peer-to-peer learning approach. This paper considers: (1) an analysis of JLN monitoring and evaluation data between 2020 and 2023 and (2) a qualitative inquiry to explore policymakers' engagement with the JLN using semi-structured interviews (n = 14) with stakeholders from 10 countries. The JLN's experience provides insights to factors that contribute to successful peer-to-peer learning approaches. JLN relies on engaging a network of practitioners with diverse experiences who organically identify and pursue a common learning agenda. Meaningful peer-to-peer learning requires dynamic, structured interactions, and alignment with windows of opportunity for implementation that enable rapid response to emerging and timely issues. Peer-to-peer learning can facilitate in-country knowledge sharing, learning and catalyse action at the institutional and health system levels.

Arctos: Community-driven innovations for managing natural and cultural history collections.

More than tools for managing physical and digital objects, museum collection management systems (CMS) serve as platforms for structuring, integrating, and making accessible the rich data embodied by natural history collections. Here we describe Arctos, a scalable community solution for managing and publishing global biological, geological, and cultural collections data for research and education. Specific goals are to: (1) Describe the core features and implementation of Arctos for a broad audience with respect to the biodiversity informatics principles that enable high quality research; (2) Highlight the unique aspects of Arctos; (3) Illustrate Arctos as a model for supporting and enhancing the Digital Extended Specimen concept; and (4) Emphasize the role of the Arctos community for improving data discovery and enabling cross-disciplinary, integrative studies within a sustainable governance model. In addition to detailing Arctos as both a community of museum professionals and a collection database platform, we discuss how Arctos achieves its richly annotated data by creating a web of knowledge with deep connections between catalog records and derived or associated data. We also highlight the value of Arctos as an educational resource. Finally, we present the financial model of fiscal sponsorship by a nonprofit organization, implemented in 2022, to ensure the long-term success and sustainability of Arctos.

Investigating the Impact of Control Modes to Competency and Engagement in Serious Game Play for Children with ADHD.

Serious games are designed to reduce symptoms of attention deficit among children with Attention Deficit/Hyperactivity Disorder (ADHD). These games predominantly use touchscreen interfaces that children with ADHD play in a sitting position, which contributes to already-problematic sedentary behaviors. In an effort to mitigate negative impacts of sedentary behavior, we set out to investigate the use of Dance Dance Revolution (DDR) mats with serious games to induce gross movements. To that end, we designed and implemented Breathtaking Glass Bridge to investigate the impact of interface (DDR vs. touchscreen) on competency and engagement in children with ADHD. Our investigation with 30 children with ADHD reveal that the DDR mat was as engaging as the conventional touchscreen interface despite relatively lower competence shown by our participants. Our study opens new research opportunities for developing and strategically using movement-based control interfaces to encourage gross movements while reducing attention deficit symptoms among children with ADHD.

Weight status and gross motor skill in kindergarten children.

PURPOSE: Childhood obesity rates are increasing globally. Physical activity is one behavioral variable that influences weight status. Participation in physical activity requires basic gross motor proficiency in early childhood. The purpose of this study was to examine the relationship between gross motor skill level and weight status in a large national representative sample of kindergarten-aged children. METHODS: Body mass index percentile ranking was calculated for 4650 children from the Early Childhood Longitudinal Study-Birth Cohort. Children were classified into underweight, healthy, overweight, or obese categories according to the Centers for Disease Control and Prevention criteria. The Early Screening Inventory Revised was used to evaluate gross motor skill level. RESULTS: Children with obesity displayed lower gross motor skill levels compared with peers of healthy weight. Largest differences were seen in locomotor and balance skills. CONCLUSIONS: Clinicians should consider adjusting gross motor expectations for locomotor or stability tasks in young children with obesity.

The effects of intrinsic foot muscle strengthening on functional mobility in older adults: A systematic review.

BACKGROUND: Weakness and disuse of intrinsic foot muscles contributes to dysfunction in foot and toe alignment and sensory input, which may lead to instability and falls in older adults. The aim of this systematic review was to report the effects of intrinsic foot muscle strengthening (IFMS) interventions on functional mobility in adults aged ≥65 years. METHODS: A systematic review was performed with searches from December 2019-February 2021 using MEDLINE, CINAHL, SPORTDiscus, Rehab and Sports Medicine Source, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. Additional sources were sought using reference scanning. Eligible sources analyzed adults aged ≥65 years (n = 1674) who were ambulatory, used a functional mobility outcome measure, and contained foot and ankle interventions that included IFMS. Literature studies regarding neurological, vestibular, cognitive, amputation, or post-surgical conditions were excluded. Studies that did not specify intrinsic foot muscle involvement were excluded. Two authors extracted relevant studies and appraised them using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: A total of 1420 articles were screened for relevance, and 16 were extracted. Five additional sources were obtained through reference scanning. Nine articles were eligible for review. PEDro scores ranged from 3 to 7 (out of 10), indicating "fair" quality of evidence. Heterogeneity of methods and data did not allow for statistical comparison. Themes extracted from sources were types of intrinsic foot strengthening interventions and parameters; outcomes on falls, balance, functional mobility; and subjective reports regarding functional mobility. CONCLUSION: Evidence reviewed was of fair quality. IFMS interventions contributed to improvements in strength, balance, mobility, and possibly reduced fall risk. There was little effect on gait. Subjective reports indicate a possible mechanism for improved mobility may be from increased proprioception and sensation.

Comparison of interventions to reduce sun exposure.

Exposure to ultraviolet (UV) light is the leading behavioral cause of skin cancer. This study evaluated the efficacy of 2 interventions to reduce UV exposure in college students prior to an opportunity for high-intensity exposure. Participants of 1 college campus were assigned randomly to 1 of 2 interventions prior to their spring holiday spent in a warm, sunny location: (1) a community-based informational campaign, or (2) a combination of the campaign and a cognitive-behavioral small group intervention. Participants of a second college campus served as a comparison group. The cognitive-behavioral group exhibited increased knowledge, more positive attitudes toward UV protection, greater advancement through stages of change, and greater protective clothing use relative to the comparison or community-education groups. The informational campaign had little apparent impact in this study.

Impact of retinopathy of prematurity screening examination on cardiorespiratory indices: a comparison of indirect ophthalmoscopy and retcam imaging.

PURPOSE: To compare the impact of retinopathy of prematurity (ROP) screening examination between a digital fundus camera and conventional binocular indirect ophthalmoscopy (BIO) using cardiorespiratory indices as a measure of distress. DESIGN: Prospective comparative (nonrandomized) interventional study. PARTICIPANTS: Eighty-six preterm infants with a birth weight of < or =1500 g or gestational age of < or =32 weeks and undergoing ROP screening were included. METHODS: Retinopathy of prematurity screening examination with BIO or the digital fundus camera was performed. Cardiovascular indices were recorded before, during, and 1 hour after examination. Race, birth weight, gender, twin status, duration of the examination, gestational age, and postconceptual age were recorded. MAIN OUTCOME MEASURES: Heart rate (HR), oxygen saturation, respiratory rate (RR), and mean blood pressure (BP). RESULTS: Thirty-four infants underwent indirect ophthalmoscopy, whereas 52 underwent digital fundus camera examination. The increase in HR and RR was significantly higher in the indirect ophthalmoscopy group than in the digital fundus camera group (P<0.05). There was a significant increase in HR and mean BP during examination in both groups (P<0.05). No clinically significant response persisted at 1 hour. Digital fundus camera examination took significantly longer (P<0.001). CONCLUSIONS: Screening for ROP with a digital fundus camera is associated with a significantly lower stress-related response than conventional indirect ophthalmoscopy.

Validation of the Kaiser Physical Activity Survey in pregnant women.

PURPOSE: Participation in physical activity during pregnancy may reduce the risk of maternal and fetal disorders. However, few studies have validated physical activity questionnaires for use during pregnancy, a time characterized by different patterns of activity than nonpregnancy. Therefore, the aim of this study was to assess the validity and reliability of the Kaiser Physical Activity Survey (KPAS) for use during pregnancy. METHODS: The KPAS, adapted from the Baecke physical activity survey, was designed specifically to assess physical activity in women. Unique features of the KPAS include the assessment of multiple domains of physical activity (household/caregiving, occupational, active living, and sports/exercise) as well as total activity. Summary KPAS indices were compared with objective (ActiGraph accelerometer by ActiGraph LLC) and subjective (Pregnancy Physical Activity Questionnaire (PPAQ)) measures of physical activity. Participants completed the self-administered PPAQ followed by the interviewer-administered KPAS and then wore the accelerometer for the following 7 d. At the end of the 7-d period, the questionnaires were repeated. RESULTS: Intraclass correlation coefficients used to measure reproducibility of the KPAS were r = 0.84 for total activity and ranged from r = 0.76 for active living activities to r = 0.86 for occupational activity. Spearman correlations between the KPAS and three published cut points used to classify accelerometer data ranged from r = 0.49-0.59 for total activity, r = 0.12-0.26 for household/caregiving, r = 0.26-0.33 for occupational activity, r = 0.31-0.36 for active living, and r = 0.34-0.51 for sports/exercise. Spearman correlations between the KPAS and the PPAQ ranged from r = 0.71 for household/caregiving to r = 0.84 for sports/exercise. CONCLUSIONS: The KPAS is a reliable and reasonably accurate instrument for estimating physical activity among pregnant women.

Health benefits of seated speed, resistance, and power training for an individual with spastic quadriplegic cerebral palsy: A case report.

Children with moderate to severe cerebral palsy are at risk for low bone mass for chronological age, which compounds risk in adulthood for progressive deformity and chronic pain. Physical activity and exercise can be a key component to optimizing bone health. In this case report we present a young adult male with non-ambulatory, spastic quadriplegia CP whom began a seated speed, resistance, and power training exercise program at age 14.5 years. Exercise program continued into adulthood as part of an active lifestyle. The individual had a history of failure to thrive, bowel and bladder incontinence, reduced bone mineral density (BMD) for age, and spinal deformity at the time exercise was initiated. Participation in the exercise program began once a week for 1.5-2 hours/session, and progressed to 3-5 times per week after two years. This exercise program is now a component of his habitual lifestyle. Over the 6 years he was followed, lumbar spine and total hip BMD Z-scores did not worsen, which may be viewed as a positive outcome given his level of gross motor impairment. Additionally, the individual reported less back pain, improved bowel and bladder control, increased energy level, and never sustained an exercise related injury. Findings from this case report suggest a regular program of seated speed, resistance, power training may promote overall well-being, are safe, and should be considered as a mechanism for optimizing bone health.

Transpalpebral proton beam radiotherapy of choroidal melanoma.

BACKGROUND: Collateral damage to upper eyelid margin during proton beam radiotherapy (PBR) for choroidal melanoma may cause squamous metaplasia of the tarsal conjunctiva with keratinisation, corneal irritation, discomfort and, rarely, corneal perforation. We evaluated transpalpebral PBR as a means of avoiding collateral damage to the upper eyelid margin without increasing the risk of failure of local tumour control. METHODS: Retrospective study of consecutive patients who underwent PBR for choroidal melanoma between 1992 and 2007 at the Royal Liverpool University Hospital and the Douglas Cyclotron at Clatterbridge Cancer Centre, UK. RESULTS: Sixty-three patients were included in this study. Mean basal tumour diameter and tumour thickness were 11.8 mm and 3.6 mm, respectively. PBR mean beam range and modulation were 26.5 mm and 16.9 mm respectively. The eyelid margin was included in the radiation field in 15 (24%) eyes. The median follow-up was 2.5 years. Local tumour recurrence developed in 2 (3.2%) patients. In these two cases that developed tumour recurrence the transpalpebral treatment did not involve the eyelid margin. Six (9.5%) patients died of metastatic disease. No eyelid or ocular surface problems developed in any of the 48 patients who were treated without eyelid rim involvement, while 7 of the 15 patients with unavoidable irradiation of the eyelid rim developed some degree of madarosis. These seven patients all received more than 26.55 proton Gy to the eyelid margin. Symptoms, such as grittiness occurred in 12% of 48 patients without eyelid margin irradiation as compared with 53% of 15 patients whose lid margin was irradiated. CONCLUSIONS: Transpalpebral PBR of choroidal melanoma avoids eyelid and ocular surface complications without increasing failure of local tumour control.

Development and validation of a Pregnancy Physical Activity Questionnaire.

PURPOSE: The effect of physical activity during pregnancy on maternal and fetal health remains controversial and studies have yet to identify the optimal dose of physical activity associated with favorable pregnancy outcomes. The aim of this study was to develop and validate a pregnancy physical activity questionnaire (PPAQ). METHODS: To ascertain the type, duration, and frequency of physical activities performed by pregnant women, three 24-h physical activity recalls were administered to 235 ethnically diverse prenatal care patients at a large tertiary care facility in western Massachusetts. The relative contribution of each activity to between-person variance in energy expenditure was used to establish the list of activities for the PPAQ. The PPAQ is self-administered and asks respondents to report the time spent participating in 32 activities including household/caregiving, occupational, sports/exercise, transportation, and inactivity. To validate the PPAQ, 54 pregnant women completed the PPAQ and then wore a Manufacturing Technology, Inc. actigraph for the following 7 d. At the end of the 7-d period, the PPAQ was repeated. RESULTS: Intraclass correlation coefficients used to measure reproducibility of the PPAQ were 0.78 for total activity, 0.82 for moderate activity, 0.81 for vigorous activity, and ranged from 0.83 for sports/exercise to 0.93 for occupational activity. Spearman correlations between the PPAQ and three published cut points used to classify actigraph data ranged from 0.08 to 0.43 for total activity, 0.25 to 0.34 for vigorous activity, 0.20 to 0.49 for moderate activity, and -0.08 to 0.22 for light-intensity activity. Correlations were higher for sports/exercise and occupational activities as compared to household/caregiving activities. CONCLUSIONS: household/caregiving activities. CONCLUSIONS: The PPAQ is a reliable instrument of physical activities during pregnancy.

Whole anterior segment proton beam radiotherapy for diffuse iris melanoma.

AIM: To report the results of whole anterior segment proton beam radiotherapy (PBR) for diffuse iris melanoma. METHODS: Between 2000 and 2011, 12 patients with iris melanoma received PBR to the entire iris and ciliary body. RESULTS: Patients had a mean age of 57 years and a median follow-up of 3.5 years (range 1-11.6 years). Tumour iris involvement was 1-4 h in five patients, 5-8 h in four and 9-12 h in three. Angle involvement was 6-8 h in five patients and 9-12 h in seven. The visual acuity (VA) before treatment was 6/5-6/6 in six patients, 6/8-6/9 in three and 6/18-6/38 in three. No tumour recurrence occurred during the follow-up period. Glaucoma treatment was required in 11 of 12 patients. The visual acuity at the last follow-up was 6/5-6/9 in five patients, 6/18-6/24 in three, 6/60-1/60 in two and no light perception in two. Four patients developed varying non-severe degrees of limbal stem cell deficiency, which was treatable with conservative measures. CONCLUSIONS: Whole anterior segment PBR is a useful alternative to enucleation for diffuse iris melanoma. Most patients will need treatment for glaucoma and some may require treatment for tear-film instability and/or stem cell failure.

Active or sedentary? Objectively measured physical activity of Latinos and implications for intervention.

BACKGROUND: Latinos have the lowest leisure-time physical activity (LTPA) rates. However, measurement of only LTPA might underestimate total physical activity. This study compares the objective physical activity of Latinos reporting high or low levels of LTPA and also compares gender differences. METHODS: Data were obtained from 148 Latinos (n = 83 women, n = 65 men). Freedson cut points were employed to determine daily minutes of activity. RESULTS: Latinos reporting high LTPA engaged in more daily minutes of vigorous and very vigorous activity than Latinos reporting low LTPA (P values < .05). There was no difference in daily minutes of moderate-intensity activity (P = .12), with both groups of Latinos meeting Centers for Disease Control and Prevention/American College of Sports Medicine guidelines. Men engaged in more daily minutes of moderate activity than women (P < .01). CONCLUSIONS: Many Latinos met physical activity guidelines even when reporting low levels of LTPA. Future studies should determine whether equivalent health benefits are achieved by meeting guidelines through LTPA and non-LTPA.