Minorities Remain Underrepresented in HIV/AIDS Research Despite Access to Clinical Trials

Background and Objective: The reasons for minority underrepresentation in HIV/AIDS clinical trials remain unclear. We aimed to evaluate the knowledge, experience, and factors that influence minority participation in HIV/AIDS studies in the United States. Methods: An anonymous, bilingual, self-administered survey on study participation was given to HIV-infected adults attending AIDS Clinical Trials Group–affiliated clinics in the United States and Puerto Rico. Chi-square tests were used to evaluate differences by race, first language, and level of education. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for factors associated with being talked to about participation in a study. Results: We analyzed 2,175 complete surveys (221 in Spanish). Among respondents, 31% were White, 40% were Black/African American (AA), and 21% were Hispanic. The overall rate of previous participation in any HIV/AIDS study was 48%. Hispanics were less likely to know about studies compared to Whites and AAs (67% vs 74% and 76%, respectively; P .001). Compared to Whites, AAs and Hispanics were less likely to have been talked to about participating in a study (76% vs 67% and 67%, respectively; P .001). The OR for being talked to about participating in a study was 0.65 (95% CI, 0.52–0.81) for AAs and 0.65 (95% CI, 0.49–0.85) for Hispanics, compared to Whites. AAs and Hispanics were more likely to state that studies were not friendly to their race (17% and 10% vs 4%; P .001). Conclusions: Minorities continue to face barriers for HIV/AIDS trial participation, even when clinical research is available. Enrollment strategies should better target minorities to improve recruitment in HIV/AIDS research.     

Proteomic Analyses of the Effects of Drugs of Abuse on Monocyte-Derived Mature Dendritic Cells

Drug abuse has become a global health concern. Understanding how drug abuse modulates the immune system and how the immune system responds to pathogens associated with drug abuse, such hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1), can be assessed by an integrated approach comparing proteomic analyses and quantitation of gene expression. Two-dimensional (2D) difference gel electrophoresis was used to determine the molecular mechanisms underlying the proteomic changes that alter normal biological processes when monocyte-derived mature dendritic cells were treated with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins including those that modulate apoptosis, protein folding, protein kinase activity, and metabolism and proteins that function as intracellular signal transduction molecules. Proteomic data were validated using a combination of quantitative, real-time PCR and Western blot analyses. These studies will help to identify the molecular mechanisms, including the expression of several functionally important classes of proteins that have emerged as potential mediators of pathogenesis. These proteins may predispose immunocompetent cells, including dendritic cells, to infection with viruses such as HCV and HIV-1, which are associated with drug abuse.     

Osteopontin: a marker for invasive oral squamous cell carcinoma but not for potentially malignant epithelial dysplasias

This study aimed to evaluate and correlate osteopontin (OPN) expression in oral squamous cell carcinoma (OSCC) and potentially malignant disorders including oral leukoplakia and oral submucous fibrosis (OSMF). Expression of OPN was investigated in 140 samples including OSCC, oral leukoplakia, and OSMF with or without dysplasia and normal oral mucosa. By using immunohistochemistry. Both intercellular and intracellular staining of the keratinocytes was considered to be positive, and intensity grading was assessed. Statistical analysis was done using analysis of variance. OPN positivity was detected in 85% cases of OSCC, 55% cases of oral leukoplakia, 35% cases of OSMF, and 60% cases of normal mucosa. These study highlights OPN as a biomarker for malignancy in the form of invasion but not to study progression from dysplasia to malignant transformation.     

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

PurposeThe study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy.Methods and MaterialsForty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017–2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed.ResultsHigh-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm³ bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences.ConclusionsOur study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.     

Improvement of Dermatochalasis and Periorbital Rhytides With a High-Energy Pulsed CO2 Laser: A Retrospective Study

Background. Upper eyelid dermatochalasis is typically treated with excisional blepharoplasty. The role of the CO₂ laser previously had been confined to that of a vaporizing, incisional, or hemostatic tool. Over the past several years, however, ablative CO₂ laser skin resurfacing has been popularized as an adjunctive treatment to blepharoplasty to minimize periorbital rhytides through its vaporizing as well as skin-tightening action.
Objective. To evaluate the safety and efficacy of a high-energy pulsed CO₂ laser as a stand-alone treatment for dermatochalasis and periorbital rhytides.
Methods. Sixty-seven patients (skin phototypes I–IV) with mild-to-severe upper eyelid dermatochalasis and periorbital rhytides received periocular CO₂ laser skin treatment. Global assessment scores of dermatochalasis and rhytides were determined by a side-by-side comparison of periocular photographs preoperatively and 1, 3, and 6 months postoperatively. In addition, caliper measurements of upper eyelids before and 1, 3, and 6 months after treatment were obtained.
Results. Both dermatochalasis and periorbital rhytides were significantly improved after periocular CO₂ laser skin resurfacing. Patients with more severe dermatochalasis and rhytides showed greater improvement after CO₂ laser treatment than did those with mild or moderate involvement. Side effects were limited to erythema and transient hyperpigmentation. No scarring, hypopigmentation, or ectropion were observed.
Conclusions. Periocular skin resurfacing with a CO₂ laser can safely and effectively improve upper eyelid dermatochalasis and periorbital rhytides.     

Massive transfusion in paediatric and adolescent trauma patients: Incidence,patient profile,and outcomes prior to a massive transfusion protocol

Objectives

The purpose of this study was to quantify the incidence, patient profile, and outcomes associated with massive transfusion in paediatric trauma patients prior to establishing a massive transfusion protocol.

Methods

We performed a retrospective review of paediatric trauma patients treated at London Heath Sciences Centre between January 1, 2006, and December 31, 2011. Inclusion criteria were Injury Severity Score (ISS) greater than 12 and age less than 18 years.

Results

435 patients met the inclusion criteria. Three hundred and fifty-six (82%) did not receive packed red blood cells in the first 24 h, 66 (15%) received a non-massive transfusion (<40 mL/kg), and 13 (3%) received a massive transfusion (>40 mL/kg). Coagulopathy of any kind was more common in massive transfusion (11/13; 85%) than non-massive (32/66; 49%) (p = 0.037). Hyperkalemia (18% versus 23%; p = 0.98) and hypocalcemia (41% versus 46%; p = 1.00) were similar in both groups. Of the 13 massively transfused patients, 9 had multisystem injuries due to a motor vehicle collision, 3 had non-accidental head injuries requiring surgical evacuation, and 1 had multiple stab wounds. In the absence of a massive transfusion protocol, only 8 of the 13 patients received both fresh frozen plasma and platelets in the first 24 h. Massive transfusion occurred in patients from across the age spectrum and was associated with severe injuries (mean ISS = 33), a higher incidence of severe head injuries (92%), longer hospital stay (mean = 36 days), and increased mortality (38%).

Conclusions

This study is the first to describe the incidence, complications, and outcomes associated with massive transfusion in paediatric trauma patients prior to a massive transfusion protocol. Massive transfusion occurred in 3% of patients and was associated with coagulopathy and poor outcomes. Protocols are needed to ensure that resuscitation occurs in a coordinated fashion and that patients are given appropriate amounts of fresh frozen plasma, platelets, and cryoprecipitate.     

The TNF-derived TIP peptide activates the epithelial sodium channel and ameliorates experimental nephrotoxic serum nephritis

1. Download : Download high-res image (407KB)
2. Download : Download full-size image

     

Detectability of stop‐signal determines magnitude of deceleration in saccade planning

An inhibitory control is exerted when the context in which a movement has been planned changes abruptly making the impending movement inappropriate. Neurons in the frontal eye field and superior colliculus steadily increase activity before a saccadic eye movement, but cease the rise below a threshold when an impending saccade is withheld in response to an unexpected stop‐signal. This type of neural modulation has been majorly considered as an outcome of a race between preparatory and inhibitory processes ramping up to reach a decision criterion. An alternative model claims that the rate of saccade planning is diminished exclusively when the stop‐signal is detected within a stipulated period. However, due to a dearth of empirical evidence in support of the latter model, it remains unclear how the detectability of the stop‐signal influences saccade inhibition. In our study, human participants selected a visual target to look at by discriminating a go‐cue. Infrequently they cancelled saccade and reported whether they saw the stop‐signal. The go‐cue and stop‐signal both were embedded in a stream of irrelevant stimuli presented in rapid succession. Participants exhibited difficulty in detection of the stop‐signal when presented almost immediately after the go‐cue. We found a robust relationship between the detectability of the stop‐signal and the odds of saccade inhibition. Saccade latency increased exponentially with the maximum time available for processing the stop‐signal before gaze shifted. A model in which the stop‐signal onset spontaneously decelerated progressive saccade planning with the magnitude proportional to its detectability accounted for the data.     

Modulation of the Proteome of Peripheral Blood Mononuclear Cells from HIV-1-Infected Patients by Drugs of Abuse

Introduction  We used proteomic analyses to assess how drug abuse modulates immunologic responses to infections with the human immunodeficiency virus type 1 (HIV-1). Methods  Two-dimensional difference gel electrophoresis was utilized to determine changes in the proteome of peripheral blood mononuclear cells (PBMC) isolated from HIV-1-positive donors that occurred after treatment with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins. We further isolated specific subpopulations of PBMC to determine which subpopulations were selectively affected by treatment with drugs of abuse. Monocytes, B cells, and T cells were positively or negatively selected from PBMC isolated from HIV-1-positive donors. Results  Our results demonstrate that cocaine and methamphetamine modulate gene expression primarily in monocytes and T cells, the primary targets of HIV-1 infection. Proteomic data were validated with quantitative, real-time polymerase chain reaction. These studies elucidate the molecular mechanisms underlying the effects of drugs of abuse on HIV-1 infections. Several functionally relevant classes of proteins were identified as potential mediators of HIV-1 pathogenesis and disease progression associated with drug abuse.