Identification of circulating antigen-specific CD4+ T lymphocytes with a CCR5+, cytotoxic phenotype in an HIV-1 long-term nonprogressor and in CMV infection

Antigen-specific CD4+ effector T cells primarily provide help for B-cell antibody responses and CD8+ cytotoxic T-lymphocyte (CTL) responses. We have found an expanded population of HIV-1 p24-specific, T-cell receptor V beta 17+, CD4+ T lymphocytes, defined by in vitro proliferative and interferon-gamma responses to a 15-mer Gag peptide, in the peripheral blood of an individual with long-term nonprogressive HIV-1 infection. Ex vivo, these cells were CCR5+ and CCR7-, consistent with an effector/memory function. Surprisingly, these cells highly expressed several proteins characteristic of cytotoxic lymphocytes, including TIA-1 (T-cell intracellular antigen 1; GMP-17/NKG7), granzymes A and B, CD161 (NKRP-1), and CD244 (C1.7/2B4). Following in vitro peptide stimulation, these cells produced interleukin 2 (IL-2) and intracellular CD40L, suggesting possible helper function, in addition to induction of perforin and cytotoxicity. A subset of cytomegalovirus (CMV)-specific CD4+ T cells in healthy adults similarly expressed these CTL markers and CCR5, ex vivo. Furthermore, this distinct subset of CD4+ T cells was significantly elevated in healthy CMV-seropositive adults, compared with CMV-seronegative individuals. These results suggest that CCR5+ CD4+ CTL may be a major effector mechanism of the immune response to viral infections in humans. Moreover, expression of CCR5 may render them particularly susceptible to cytopathic effects during progressive HIV-1 infection.     

The spectrum of renal diseases with lupus-like features: a single-center study

BackgroundA subset of patients without overt systemic lupus erythematosus (SLE) present with biopsy findings typically seen in lupus nephritis (LN). Although a minority eventually develops SLE, many do not. It remains unclear how to classify or treat these patients. Our study attempted to further understand the clinical and pathological characteristics of cases with lupus-like nephritis (LLN).MethodsAmong 2700 native kidney biopsies interpreted at University of Rochester Medical Center (URMC) from 2010 to 2019, we identified 27 patients with biopsies showing lupus-like features (LL-fx) and 96 with LN. Of those with LL-fx, 17 were idiopathic LLN and 10 were associated with a secondary etiology (e.g., infection/drugs).ResultsAt the time of biopsy, the LLN-group tended to be slightly older (44 vs. 35), male (58.8 vs. 17.7%, p = .041), and Caucasian (47.0 vs. 28.1%, p = .005). Chronic kidney disease was the most common biopsy indication in LLN (21.4 vs. 2.8%, p = .001). Both LN and LLN presented with nephrotic-range proteinuria (mean 5.73 vs. 4.40 g/d), and elevated serum creatinine (mean 1.66 vs. 1.47 mg/dL). Tubuloreticular inclusions (TRIs; p < .001) and fibrous crescents (p = .04) were more often seen in LN, while more tubulointerstitial scarring was seen in LLN (p = .011). At mean follow-up of 1684 d (range: 31–4323), none of the LLN patients developed ESRD. A subset of both LN and cases with LL-fx overlapped with other autoimmune diseases.ConclusionsLupus-like pathologic features are seen in a wide array of disease processes. The findings suggest that LLN may be a manifestation of an autoimmune process that overlaps with SLE.     

Factor structure of the WAIS-R for an incarcerated population

The factor structure of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) for a large sample of incarcerated individuals (N = 234) was investigated. A principal components analysis followed by Varimax rotation identified the familiar Perceptual Organization and Verbal Comprehension factors. Coefficients of congruence between the current factors and those of the WAIS-R standardization sample indicate a high degree of correspondence. Thus, empirical support was provided for interpretation of WAIS-R Performance and Verbal IQs in this population.     

Compliance with and acceptability of two fortified balanced energy protein supplements among pregnant women in rural Nepal

Some evidence suggests that balanced energy protein (BEP) supplements taken during pregnancy and lactation can have positive effects on birth outcomes such as small‐for‐gestational age and birthweight, but more evidence is needed on the long‐term use and acceptability of such supplements. We conducted a mixed‐methods formative research study to assess and compare compliance with and acceptability of two BEP supplements, a lipid‐based peanut paste and a biscuit, to identify BEP supplements for subsequent inclusion in an efficacy trial. We conducted an 8‐week feeding trial of daily supplementation among two groups of 40 pregnant women each in rural Nepal. Compliance data were collected and supplements distributed at the weekly visits. Sensory properties of the supplements were assessed using a 7‐point Likert scale. In addition, in‐depth interviews with women (n = 16), family members (n = 6) and health workers (n = 6) and focus group discussions (FGDs) (n = 4) were conducted to explore themes related to general use and intention of future use of the supplement. Overall self‐reported compliance was high: medians of 91.1% in the lipid‐based peanut paste group and 96.4% in the biscuit group. Both supplements were rated highly on overall likability (median score 6/7) and sensory properties. Qualitative findings showed that sustained use of the supplements was attributed to expected health benefits, favourable sensory attributes, and family support. The FGDs suggested providing the option to choose between more than one type/flavour of supplements to improve compliance. Sharing was mostly evident in the first week with higher sharing reported in the biscuit group.     

Replication Kinetics for a Reporter Merkel Cell Polyomavirus

Merkel cell polyomavirus (MCV) causes one of the most aggressive human skin cancers, but laboratory studies on MCV replication have proven technically difficult. We report the first recombinase-mediated MCV minicircle (MCVmc) system that generates high levels of circularized virus, allowing facile MCV genetic manipulation and characterization of viral gene expression kinetics during replication. Mutations to Fbw7, Skp2, β-TrCP and hVam6p interaction sites, or to the stem loop sequence for the MCV-encoded miRNA precursor, markedly increase viral replication, whereas point mutation to an origin-binding site eliminates active virus replication. To further increase the utility of this system, an mScarlet fusion protein was inserted into the VP1 c-terminus to generate a non-infectious reporter virus for studies on virus kinetics. When this reporter virus genome is heterologously expressed together with MCV VP1 and VP2, virus-like particles are generated. The reporter virus genome is encapsidated and can be used at lower biosafety levels for one-round infection studies. Our findings reveal that MCV has multiple, self-encoded viral restriction mechanisms to promote viral latency over lytic replication, and these mechanisms are now amenable to examination using a recombinase technology.     

A systems approach to investigating interpersonal strife

Investigated the relationships between computer-simulated, in-vitro interactional personality behavior and various indices of interpersonal relationships using data collected from 31 families. Interpersonal strife scores for each of 31 family triads developed via mathematical simulation using a systems approach correlated significantly with 6 of the 10 personal relationship variables. Stepwise regression analysis showed that strife for this sample was allied most closely with rigid, unstable interpersonal interactions. It was concluded that (1) mathematical simulation of interpersonal behavior shows validity for group behavior as well as dyadic behavior; and (2) the systems approach offers a unique, in-vitro way of studying and diagnosing interpersonal difficulties.     

Do patients like psychometric testing by computer?

Programmed a micro-computer to administer and score the Crown-Crisp Experiential Index (CCEI) (Crown & Crisp, 1979) for a study of the psychological state of 59 newly delivered mothers. This publication reports the findings of a separate paper-and-pencil questionnaire assessment of the patients' attitudes to the computer itself. The 59 patients were almost unanimous in finding the computer acceptable and easy to use; only 1 S minded using it. None found the instructions difficult to understand, and only 1 had difficulty in reading them. Only 2 would object to using the computer again.     

The Utility of a Composite Biological Endpoint in HIV/STI Prevention Trials

A human immunodeficiency virus (HIV) as a biological endpoint in HIV prevention trials may not be feasible, so investigators have used surrogate biological outcomes. In a multisite trial, the epidemiology of STIs may be different across sites and preclude using one STI as the outcome. This study explored using a composite STI outcome to address that problem. The combined biological endpoint was the incidence of any of six new STIs (chlamydia, gonorrhea, trichomonas (women only), syphilis, herpes simplex virus type 2 infection and HIV) during a 24-month follow up period. We investigated how a composite STI outcome would perform compared to single and dual STI outcomes under various conditions. We simulated outcomes for four populations that represented a wide range of sex and age distributions, and STI prevalences. The simulations demonstrated that a combined biologic outcome was superior to single and dual STI outcomes in assessing intervention effects in 82 % of the cases. A composite biological outcome was effective in detecting intervention effects and might allow more investigations to incorporate multiple biological outcomes in the assessment of behavioral intervention trials for HIV prevention.     

Can physical activity improve the health of the overweight without weight loss?

The prevalence of obesity continues to rise, with over one quarter of the UK adult population in 2010 being classified as obese. Obesity has a severe impact on health and is associated with an array of serious health conditions. Physical inactivity is another major contributor to the global burden of disease and is also associated with a range of negative health outcomes. Research suggests that maintaining or improving fitness through physical activity is associated with a lower risk of developing obesity‐related conditions regardless of weight change. Therefore, healthcare professionals should place an emphasis on advising their patients to increase their physical activity levels to meet UK guidelines, as well as on eating a healthy, balanced diet and maintaining a healthy bodyweight.