Planning and implementing a statewide soccer HIV awareness and health promotion intervention for African-born men living in the United States
The increasing number of African-born individuals newly diagnosed with HIV in Massachusetts led to a grassroots effort to advocate for needed resources, policies, and programs. This article describes the African Health Cup (AHC), one of the major innovative programs developed by Africans For Improved Access (AFIA) in collaboration with community members.
Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth
OBJECTIVES: We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.
METHODS: Ninety subjects 4 to < 25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.
RESULTS: At entry, 26 (29%) subjects had pH1N1 protective HAI titers ( > /=1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p /=1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI < 1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNgamma, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNgamma responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.
CONCLUSIONS: HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI>/=1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00992836.
The second Annual Scientific Meeting of the Pan Arab Interventional Radiology Society (PAIRS), held March 12-14, 2015, was a step above the inaugural edition, and opened new concepts for development.
Cambodia is located in Southeast Asia on the Indochina Peninsula and borders Vietnam, Laos, Thailand and the Gulf of Thailand (Figure 1). With a total area of 69,898 square miles and population of 15,458,332, Cambodia’s population density has steadily increased since 1980. The country’s annual rate of urbanization is 2.65 %. As of 2014, 20.5% of the population lives in an urban setting. The estimated population growth rate is 1.63% (1).
The capital of Cambodia is Phnom Penh, which is located in the southern part of the country. Other major cities include Battambang and Siem Reap, both of which have populations over 150,000. There are officially 24 provinces and one municipality (Phnom Penh). However, many consider Phnom Penh to be its own province. As a result, some research puts the number of Cambodian provinces at 25.
The climate is tropical with two seasons: monsoon season (May to November) and dry season (December to April). Temperatures range from approximately 70 to 95°F. Cambodia’s economy largely depends on the garment industry, tourism, construction, real estate and agriculture.
Cambodia gained independence from France in 1953 and was first ruled by a constitutional monarchy under King Norodom Sihanouk. After a five-year struggle starting in 1970, the Khmer Rouge captured Phnom Penh in 1975. Pol Pot, the leader of the Khmer Rouge, oversaw a brutal regime that, through executions and forced labor, was responsible for the deaths of at least 1.5 million Cambodians. The Vietnamese drove out the Khmer Rouge in 1979. After years of Vietnamese occupation, the 1991 Paris Peace Accords established a ceasefire and a democratic framework for the country. By 1993 elections established a new coalition government; yet, political instability and violence persisted throughout the 1990s. Cambodia most recently held elections in 2013, as a multiparty democracy under a constitutional monarchy.
The devastation caused by the Khmer Rouge has had long-lasting negative effects on Cambodia’s political and economic systems, as well as to its infrastructure, and public health. Despite this, Cambodia has made measurable improvements. At the end of Khmer Rouge rule in 1980, life expectancy was 30 years (1). Political stabilization, economic improvement and a growing healthcare system improved the life expectancy to 63.78 years by 2015 (2). The physician density remains low, at 0.17 physicians per 1,000 people (2). As of 2012, there were eight national hospitals and three levels of referral hospitals in the public sector. Referral hospitals are categorized by three levels of Complementary Package of Activity (CPA): 1) CPA-1 hospitals do not perform surgery; 2) CPA-2 hospitals perform surgeries but with more limited specialized services; and 3) CPA-3 hospitals perform surgery with more specialized services. There are 26 CPA-3 hospitals in Cambodia (3). As of 2011 there were 2,391 doctors, 8,433 nurses and 3,748 midwives (3). There are also NGOs that run hospitals throughout Cambodia, as well as private sector health care facilities.
Systems and Psychosocial Advances Research Center Annual Report to the Massachusetts Department of Mental Health 2014-2015
We are grateful to the Massachusetts Department of Mental Health (DMH) for its continued support of the University of Massachusetts Medical School’s (UMMS) DMH Research Center of Excellence, the Systems and Psychosocial Advances Research Center (SPARC). We continue to leverage the DMH investment to support innovative, recovery-oriented, state-of-the-art psychosocial and systems research. Highlights of Fiscal Year 2015 include another increase in research dollars awarded through new grants and contracts, and the end of our three-year Strategic Plan to guide our growth and trajectory over the coming years.
The Systems and Psychosocial Advances Research Center conducts research to enhance services, improve the quality of life, and promote recovery for people with behavioral health conditions. Our research informs and advises individuals with lived experience and their families, providers, administrators and policy-makers navigating the behavioral health landscape in the Commonwealth and beyond. SPARC was created in 1993 when it was designated a Center of Excellence for Psychosocial and Systems Research by the Massachusetts DMH. Our mission mirrors the DMH commitment to collaborating with other state agencies, consumers, families, advocates, providers, and communities. DMH and SPARC are aligned in their vision of promoting mental health through early intervention, treatment, education, policy, and regulation to provide opportunities for citizens of the Commonwealth to live full and productive lives.
Single-Molecule Imaging Reveals that Argonaute Reshapes the Binding Properties of Its Nucleic Acid Guides
Argonaute proteins repress gene expression and defend against foreign nucleic acids using short RNAs or DNAs to specify the correct target RNA or DNA sequence. We have developed single-molecule methods to analyze target binding and cleavage mediated by the Argonaute:guide complex, RISC. We find that both eukaryotic and prokaryotic Argonaute proteins reshape the fundamental properties of RNA:RNA, RNA:DNA, and DNA:DNA hybridization—a small RNA or DNA bound to Argonaute as a guide no longer follows the well-established rules by which oligonucleotides find, bind, and dissociate from complementary nucleic acid sequences. Argonautes distinguish substrates from targets with similar complementarity. Mouse AGO2, for example, binds tighter to miRNA targets than its RNAi cleavage product, even though the cleaved product contains more base pairs. By re-writing the rules for nucleic acid hybridization, Argonautes allow oligonucleotides to serve as specificity determinants with thermodynamic and kinetic properties more typical of RNA-binding proteins than of RNA or DNA.
BACKGROUND: The main cause of brachioradial pruritus (BRP) is not known but there is evidence to suggest that BRP may arise in the nervous system. Cervical spine disease may be an important contributing factor.
OBJECTIVE: Our aim was to determine whether spine pathology is associated with BRP. METHODS: Medical charts of patients with BRP seen in the Division of Dermatology of the University of Massachusetts Medical Center between the years of 1993 and 2000 were retrospectively analyzed. On the basis of clinical index of suspicion, some patients had undergone radiography of the spine.
RESULTS: Of 22 patients with BRP, 11 had cervical spine radiographs. The radiographs showed cervical nnspine disease that could be correlated with the location of pruritus in each of these 11 patients.
CONCLUSIONS: Patients with BRP may have underlying cervical spine pathology. Whether this association is causal or coincidental remains to be determined.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Case: An otherwise healthy 55-year-old man reports that he has been itchy all over for 6 months. The itch interferes with falling asleep and wakes him repeatedly during the night. Initially, there was no rash, but during the past 4 months, itchy nodules and plaques have developed on his back, arms, and legs. Treatment with sedating and nonsedating oral antihistamines and topical glucocorticoids has had no effect. How would you evaluate and manage this case?
Brachioradial pruritus (BRP) is a form of neuropathic itch characterized by localized itching, burning, stinging, and tingling sensations on the dorsolateral aspect of the forearm and upper arms. Herein we present a case series of 8 patients with BRP-triggered generalized pruritus.
Article snippet: Not all itches arise in the skin. Take, for example, notalgia paraesthetica (NP) and brachioradial pruritus (BRP). Formerly considered rare, these two ‘named itches’ are in fact rather common... It is now generally accepted that BRP and NP arise not in the skin but in the nervous system. NP and BRP are neurogenic in origin,neuropathic in character...
Vitiligo is an autoimmune disease of the skin in which melanocytes are destroyed by antigen-specific T cells, resulting in patchy depigmentation. Although adaptive immunity plays a clear role in disease progression, initiating factors are largely unknown. Many studies report that cellular stress pathways are dysregulated in melanocytes from vitiligo patients, suggesting that melanocyte-intrinsic defects participate in disease pathogenesis. Recent studies reveal that melanocyte stress generates damage-associated molecular patterns that activate innate immunity, thus connecting stress to organ-specific inflammation. Genetic studies in vitiligo support a role for stress, innate immunity, and adaptive mechanisms. Here, we discuss advances in the field that highlight how cellular stress, endogenous danger signals, and innate immune activation promote the onset of vitiligo.
The Integrated Skin Exam film: an educational intervention to promote early detection of melanoma by medical students
BACKGROUND: Knowledge of the skin cancer examination (SCE) and its practice remain relevant competency gaps among medical students.
OBJECTIVE: We elaborate on a method of SCE known as the Integrated Skin Exam and discuss the development of an instructional film that illustrates its principles. We assess the tool's effect on knowledge, attitudes, and perceptions related to the SCE.
METHODS: Second-year students among 8 randomized schools viewed the film and completed pre-post questionnaires.
RESULTS: After viewing The Integrated Skin Exam film, students demonstrated improved melanoma knowledge, including identification of high-risk demographic groups (61% vs 42.9%, P < .001), high-risk anatomic sites in women (88.6% vs 46.5%, P < .001) and men (92.1% vs 34.8%, P < .001), and the ABCDEs of melanoma (98.4% vs 91.2%, P < .001). Students demonstrated increased confidence in the SCE (66.93% vs 16.40%, P < .001) and augmented intentions to practice it (99.05% vs 13.9%, P < .001). A greater proportion (70.4% vs 41.9%, P < .001) of students thought less than 3 minutes were required to integrate SCE into the routine examination.
LIMITATIONS: Longitudinal impact of the film was not assessed.
CONCLUSION: The Integrated Skin Exam film introduces an integrated approach to the SCE that addresses knowledge gaps, mitigates perceived barriers, and augments intention related to practice of the SCE.
Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and are routinely used for disease diagnosis. Protein citrullination is also increased in cancer and other autoimmune disorders, suggesting that citrullinated proteins may serve as biomarkers for diseases beyond RA. To identify these citrullinated proteins, we developed biotin-conjugated phenylglyoxal (biotin-PG). Using this probe and our platform technology, we identified > 50 intracellular citrullinated proteins. More than 20 of these are involved in RNA splicing, suggesting, for the first time, that citrullination modulates RNA biology. Overall, this chemical proteomic platform will play a key role in furthering our understanding of protein citrullination in rheumatoid arthritis and potentially a wider spectrum of inflammatory diseases.
Ulcerative colitis (UC) is a chronic disease, in which the lining of the colon becomes inflamed and develops ulcers leading to abdominal pain, diarrhea, and rectal bleeding. The extent of these symptoms depends on disease severity. The protein arginine deiminase (PAD) family of enzymes converts peptidyl-Arginine to peptidyl-Citrulline through citrullination. PADs are dysregulated, with abnormal citrullination in many diseases, including UC and colorectal cancer (CRC). We have developed the small molecule, pan-PAD inhibitor, Chlor-amidine (Cl-amidine), with multiple goals, including treating UC and preventing CRC. Building off our recent results showing that: 1) Cl-amidine suppresses colitis in vivo in a dextran sulfate sodium (DSS) mouse model; and 2) Cl-amidine induces microRNA (miR)-16 in vitro causing cell cycle arrest, we tested the hypothesis that Cl-amidine can prevent tumorigenesis and that miR-16 induction, by Cl-amidine, may be involved in vivo. Consistent with our hypothesis, we present evidence that Cl-amidine, delivered in the drinking water, prevents colon tumorigenesis in our mouse model of colitis-associated CRC where mice are given carcinogenic azoxymethane (AOM), followed by multiple cycles of 2% DSS to induce colitis. To begin identifying mechanisms, we examined the effects of Cl-amidine on miR-16. Results show miR-16 suppression during the colitis-to-cancer sequence in colon epithelial cells, which was rescued by drinking Cl-amidine. Likewise, Ki67 and cellular proliferation targets of miR-16 (Cyclins D1 and E1) were suppressed by Cl-amidine. The decrease in cell proliferation markers and increase in tumor suppressor miRNA expression potentially define a mechanism of how Cl-amidine is suppressing tumorigenesis in vivo.
Protein arginine phosphorylation is a post-translational modification (PTM) that is important for bacterial growth and virulence. Despite its biological relevance, the intrinsic acid lability of phosphoarginine (pArg) has impaired studies of this novel PTM. Herein, we report for the first time the development of phosphonate amidines and sulfonate amidines as isosteres of pArg and then use these mimics as haptens to develop the first high-affinity sequence independent anti-pArg specific antibody. Employing this anti-pArg antibody, we further showed that arginine phosphorylation is induced in Bacillus subtilis during oxidative stress. Overall, we expect this antibody to see widespread use in analyzing the biological significance of arginine phosphorylation. Additionally, the chemistry reported here will facilitate the generation of pArg mimetics as highly potent inhibitors of the enzymes that catalyze arginine phosphorylation/dephosphorylation.
Breast Ultrasound Following a Positive Clinical Breast Examination: Does It Have a Role in Low- and Middle-Income Countries?
Purpose: Breast cancer is the most common cancer among women worldwide, with an estimated 1.7 million new cases occurring in 2012. The majority of cases and deaths occur in low- and middle-income countries (LMICs), where population-based mammography screening is not available and countries must rely on clinical breast examination (CBE). Since ultrasound has the potential to reduce unnecessary biopsies by triaging women with palpable or focal breast findings at CBE, we searched for evidence in the literature on the effectiveness of ultrasound in detecting potential breast cancer following positive CBE findings.
Methods: We reviewed the literature from 2000 to 2014 for evidence on the performance of breast ultrasound, in the absence of mammography, used to evaluate women after a positive CBE. From the studies meeting our inclusion/exclusion criteria for our analysis, we extracted data on the study design, location, ultrasound transducer parameters, patient age, method for determining positive and negative cases, and number of malignancies detected/total number of women studied.
Results: We found 15 studies matching our inclusion/exclusion criteria, 9 from high-income countries and 6 from LMICs. Despite considerable variability in study design and patient populations, breast ultrasound consistently showed high sensitivity (median = 94 percent) and specificity (median = 80 percent) for detecting breast cancer and identifying normal and benign findings not requiring a biopsy. Clear patterns related to transducer frequency or income level were not discernible given the variations in patient populations and final diagnostic determinations.
Conclusion: Our systematic review suggests that breast ultrasound following a positive CBE may be a powerful diagnostic test to determine those who do or do not need biopsy. We encourage further research in breast ultrasound use after a positive CBE in LMICs to assess the accuracy of ultrasound in these settings and the feasibility of widespread implementation.
Falls remain one of the most reportable, serious and costly type of adverse events costing an estimated $3,500 to $27,000 depending on the injury. The research often focuses on the elderly and their risk for falls and injury. Increasingly higher rates of falls are being reported in the middle-age inpatient 45 to 64 years of age. While predictors of falls and injuries have been studied across all adult inpatients, research has not specifically addressed fall risk characteristics in the middle-age. The World Health Organization’s (WHO), “Risk factor model for fall in older age”, framework was adapted for the middle-age inpatient. This framework identifies extrinsic and intrinsic variables from four risk factor groupings of biological, socioeconomic, behavioral, environmental and related outcomes to describe characteristics of the middle-age inpatient’s fall injury risk. Hitcho et al. (2004) seminal article was also used to identify pertinent inpatient characteristics. The purpose of this exploratory retrospective quantitative study described fall risk factors specific to the middle-age inpatient. The aims: (1) described risk factors of falls and fall injury; (2) described unit specific data, fall numbers with type of falls, injuries from falls, and prevention strategies (3) compare the incidence of fall and injury rates in the middle-age (45- 64) patients to the other hospital adult age-groups (ages 21-44 and 65-90). This study used Retrospective hospital occurrence data to identify middle-age inpatient falls and related characteristics reported by staff. Chart review of inpatient falls identified 439 individual falls occurring from January 2012 through July 2014. The study sample included inpatients that fell either one-time or had a repeat fall during the study period. Analysis for data included use of descriptive statistics, crosstabs, and Poisson regression. Outcomes collected included demographics, admitting diagnosis, chief complaints, cormorbities, and discharge status, type of falls and areas of falls. There was no significant difference in rates of falls between units or in staffing ratios that had a bearing on the middle-age inpatient. Fall prevention interventions were found to be universally applied, not specific to the individual, nor based on outcomes of risk screening of anticipated physiological risk factors. In comparison of the middle-age inpatient population with those age 65 -90 years of age the rates per 1000 patient days for both falls (p=.637) and injuries (p=.626) had no significant difference. Males fell at a significantly higher rate (p=.000) than females in the middle-age inpatient and those aged 64-90 years. The middleage inpatient fell at an alarming rate of 42% of all falls.
staffing ratios that had a bearing on the middle-age inpatient. Fall prevention interventions were found to be universally applied, not specific to the individual, nor based on outcomes of risk screening of anticipated physiological risk factors. In comparison of the middle-age inpatient population with those age 65 -90 years of age the rates per 1000 patient days for both falls (p=.637) and injuries (p=.626) had no significant difference. Males fell at a significantly higher rate (p=.000) than females in the middle-age inpatient and those aged 64-90 years. The middle age inpatient fell at an alarming rate of 42% of all falls.
This research provided insight into a population with acute and multiple chronic disease conditions and comorbidities that contribute to altered mental status, abnormal gait and frequently awaking at night to void. This population often overestimates their limitations and strives to maintain their autonomy. The age of the patient should not influence staff assessment of alertness and orientation. The findings of the characteristics in this research provide rich information for further research in how to include the middle-age patient in clinical decision making and education of this age group.
This qualitative descriptive (QD) study examined the experience of the woman newly diagnosed with obstructive sleep apnea (OSA). The study employed Leventhal’s Self- Regulatory Theory to understand women’s illness representation of OSA, cognitive and emotional coping, and situational appraisal skills in coming to terms with OSA. The specific aims were to: 1) Describe the illness representation of women with a recent diagnosis (within one year) of OSA; 2) Describe the cognitive perceptions and emotional response to diagnosis and treatment of OSA in this sample of women; and, 3) Describe the meaning of OSA and the coping strategies used by this sample of women.
The overarching theme of this study of a life-altering diagnosis required participants to process the health threatening information in both a conceptual and concrete process for dealing with both the physical and emotional aspects. The first two subthemes that emerged were Making sense of it, and Making it work as the women came to terms with their symptoms, diagnosis, and adapted to their treatment. For this sample of women, both acceptance (acknowledging the diagnosis of OSA and embracing treatment), and denial (not convinced of diagnosis or need for treatment, seeking alternatives) were factors in how they made sense of the situation. The making it work subtheme dealt with the women’s experiences adapting to treatment both physically and emotionally, including the appraisal, reconsideration and adjustments when they encountered difficulties and delays. A fluid iterative process included women participants describing how they appraised their situation often moving back and forth between acceptance, denial, seeking alternatives, struggling with treatment and moving forward. In both of these subthemes, family support and the stigma of OSA and CPAP were involved in how the women accepted and adapted to treatment. The third subtheme that emerged was Paying it forward as many women felt the obligation to help themselves by adapting a healthier lifestyle for themselves, their families and to assist others impacted by OSA. Women spoke of paying it forward by offering information and support to others not yet diagnosed, or are struggling with diagnosis and treatment. Many of these women were staunch advocates for other women to be tested, for HCPs to be more aware, to be more attuned to women’s sleep history, and to refer women for treatment. Implications of these findings include enhancing recognition and awareness by women of OSA symptoms, the need for diagnostic evaluation, and partner awareness as an important component of diagnosis and successful treatment for women.
Study findings support recognition of women’s presentation of OSA including unusual symptoms for earlier diagnosis and treatment. Sleep partner awareness and support appear to be relevant to women in acceptance of a life altering diagnosis. Further exploration of modifiable factors such as prompt diagnosis and individualized treatment of women with OSA could also impact potential co-morbidities. Provision of further education and awareness by HCPs and insurance companies that women may not present with classic symptoms of OSA is also needed. Targeted interventions specific to women’s experiences with OSA include development of screening tools, care guidelines and treatments that enhance applicability, acceptability, and patient satisfaction. Future advocacy work will also require supporting women in “paying it forward” to help other women diagnosed with OSA.
IMP3 (insulin-like growth factor-2 mRNA binding protein 3) is an oncofetal protein whose expression is prognostic for poor outcome in several cancers. Although IMP3 is expressed preferentially in triple-negative breast cancer (TNBC), its function is poorly understood. We observed that IMP3 expression is significantly higher in tumor initiating than in non-tumor initiating breast cancer cells and we demonstrate that IMP3 contributes to self-renewal and tumor initiation, properties associated with cancer stem cells (CSCs). The mechanism by which IMP3 contributes to this phenotype involves its ability to induce the stem cell factor SOX2. IMP3 does not interact with SOX2 mRNA significantly or regulate SOX2 expression directly. We discovered that IMP3 binds avidly to SNAI2 (SLUG) mRNA and regulates its expression by binding to the 5' UTR. This finding is significant because SLUG has been implicated in breast CSCs and TNBC. Moreover, we show that SOX2 is a transcriptional target of SLUG. These data establish a novel mechanism of breast tumor initiation involving IMP3 and they provide a rationale for its association with aggressive disease and poor outcome.