Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe "Risk" Messaging and Normalize Preventative Health.

Pre-exposure prophylaxis (PrEP) is an effective form of HIV prevention, but young sexual minority men face myriad barriers to PrEP uptake. Participants (n = 202) completed a survey on healthcare experiences and beliefs about HIV and PrEP. While 98% of the sample knew about PrEP, only 23.2% reported currently taking PrEP. Participants were more likely to be taking PrEP if they received PrEP information from a healthcare provider and endorsed STI-related risk compensation. Conversely, PrEP uptake was less likely among those with concerns about medication use and adherence. While there were no racial/ethnic differences in PrEP uptake, there were differences in correlates of PrEP use for White participants and participants of color. To facilitate PrEP uptake, clinicians should provide PrEP education and screen all patients for PrEP candidacy. Additionally, public health messaging must reframe HIV "risk", highlight benefits of STI testing, and emphasize the importance of preventive healthcare for SMM.

"Worn out": Coping strategies for managing antiretroviral treatment fatigue among urban people of color living with HIV who were recently disengaged from outpatient HIV care.

Antiretroviral-related treatment fatigue is inconsistently defined in the literature on barriers to ART adherence. Research suggests that treatment fatigue is a salient challenge for people struggling with antiretroviral therapy adherence, but little is known about how people living with HIV attempt to manage this fatigue. Twenty-seven semi-structured interviews were conducted with low-income people of color living with HIV in NYC that were currently, or recently, disengaged from HIV care. The findings from this exploratory study suggest that treatment fatigue was common and that participants devised personal strategies to overcome it. These strategies included using reminder programs, requesting weekly rather than monthly pill quantities, and taking "pill holidays". The varied nature- and varying levels of effectiveness- of these strategies highlight the need for specific programming to provide tailored support. Future research should examine treatment fatigue as a specific subtype of adherence challenge, and aim to define pill fatigue clearly.

Expression of stress proteins alpha B-crystallin, ubiquitin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys.

Ubiquitin and alpha B-crystallin belong to a class of proteins which are overexpressed in a variety of human neuropathological conditions associated with increased cellular stress. In this study we have examined the brains of aged rhesus monkeys (Macaca mulatta; n = 10, mean age: 29.7 years) using antibodies against the stress proteins ubiquitin, alpha B-crystallin, and heat shock protein 27 (hsp27). Here, we demonstrate an increased expression of ubiquitin, alpha B-crystallin, and hsp27 in spheroid bodies predominantly localized in the globus pallidus and pars reticulata of the substantia nigra. A portion of the pallido-nigral spheroids also contained ferric iron as highlighted by Perls' staining. On the basis of these findings we advance the hypothesis that expression of ubiquitin, alpha B-crystallin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys represents a stress response possibly related to increased iron-mediated oxidative stress.

Late cataractogenesis in rhesus monkeys irradiated with protons and radiogenic cataract in other species.

Rhesus monkeys (Macaca mulatta) which were irradiated at ca. 2 years of age with acute doses (less than or equal to 5 Gy) of protons (32-2300 MeV) are exhibiting the late progressive phase of radiation cataractogenesis 20-24 years after exposure, the period during which we have been monitoring the sequelae of irradiation of the lens. The median life span of the primate is approximately 24 years. Analogous late ocular changes also occur in a similar period of the lifetimes of New Zealand White (NZW) rabbits (Oryctolagus cuniculus) exposed at 8-10 weeks of age to 460-MeV 56Fe ions. In this experiment, which has been in progress for ca. 6 years, we are following the development of radiation-induced lenticular opacification (cataractogenic profiles) throughout the life span. The median life span of the lagomorph is 5-7 years. Cataractogenic profiles for NZW rabbits irradiated with 20Ne and 40Ar ions and 60Co gamma photons were obtained previously. Reference is also made to measurements of the cataractogenic profiles of a short-lived rodent, the Fischer 344 rat (Rattus norvegicus) during the first year after exposure at 8-10 weeks of age to spread-Bragg-peak protons of 55 MeV nominal energy. The median life span of the rodent is reported to be 2-3 years.

Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta).

We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

Comparison of optical coherence tomography imaging of cataracts with histopathology.

This paper presents a comparison of in vivo optical coherence tomography (OCT) captured cataract images to subsequent histopathological examination of the lenticular opacities. OCT imaging was performed on anesthetized Rhesus monkeys, known as the delayed effects colony (DEC), with documented cataracts. These monkeys were exposed to several types of radiation during the mid and late 1960s. The radiation and age related cataracts in these animals were closely monitored using a unique grading system developed specifically for the DEC. In addition to this system, a modified version of a common cataract grading scheme for use in humans was applied. Of the original 18 monkeys imaged, lenses were collected at necropsy from seven of these animals, processed, and compared to OCT images. Results showed a direct correlation between the vertical OCT images and the cataractous lesions seen on corresponding histopathologic sections of the lenses. Based on the images obtained and their corresponding documented comparison to histopathology, OCT showed tremendous potential to aid identification and characterization of cataracts. There can be artifactual problems with the images related to movement and shadows produced by opacities. However, with the advent of increased speed in imaging and multiplanar imaging, these disadvantages may easily be overcome. © 1999 Society of Photo-Optical Instrumentation Engineers.

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys.

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys.

The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

Quantitation of heavy ion damage to the mammalian brain: some preliminary findings.

Histological preparations of brains from rabbits and mice exposed to different doses of various HZE particles or to low-LET photons have been subjected to preliminary quantitation of radiation-induced morphometric changes. Computer assisted measurements of several brain structures and cell types have been made using the KONTRON Automated Interactive Measurement System (IBAS, Carl Zeiss, Inc., Thornwood, N.Y. 10594 U.S.A.). New Zealand white rabbits irradiated at approximately 6 weeks of age were euthanatized 6.5-25 months after exposure to 60Co gamma photons (LET infinity = approximately 0.3 keV/micrometer, 20Ne particles (LET infinity = 35 +/- 3 keV/micrometer), or 40Ar particles (LET infinity = 90 +/- 5 keV/micrometer). Measurements of stained sections of the olfactory bulbs of those animals indicate that the mean size (volume) of olfactory glomeruli is reduced in a dose-dependent (and perhaps an LET-dependent) manner as soon as 6.5 months after irradiation. Differences between mean volumes of additional structures have been noted when histological preparations of control mouse brains were compared with irradiated specimens. Quantitation of intermediate and late changes in nervous (and other) tissues exposed to low- and high-LET radiations will improve our ability to predict late effects in tissues of astronauts and others exposed to the radiation hazards of the space environment.

The quantification of wound healing as a method to assess late radiation damage in primate skin exposed to high-energy protons.

In an experiment examining the effects of space radiations on primates, different groups of rhesus monkeys (Macaca mulatta) were exposed to single whole-body doses of 32- or 55-MeV protons. Survivors of those exposures, together with age-matched controls, have been monitored continuously since 1964 and 1965. Late effects of nominal proton doses ranging from 2-6 Gray have been measured in vitro using skin fibroblasts from the animals. A logical extension of that study is reported here, and it involves observations of wound healing after 3-mm diameter dermal punches were removed from the ears (pinnae) of control and irradiated monkeys. Tendencies in the reduction of competence to repair cutaneous wounds have been revealed by the initial examinations of animals that received doses greater than 2 Gy more than 2 decades earlier. These trends indicate that this method of assessing radiation damage to skin exposed to high-energy radiations warrants further study.

Morphometric studies of heavy ion damage in the brains of rodents.

As an approach to determining the relative biological effectiveness (RBE) of each of five different heavy ions for the mammalian brain, histological preparations of brains from mice exposed to various HZE particles at different doses and primary LETinfinity values were examined by means of semi-automated image analysis for volume changes in specific regions of the olfactory bulb. The mice were irradiated at 100 days of age and euthanatized about 500 days (16 months) later. Exposures were: 60Co gamma photons (LETinfinity = 1-2 keV/micrometer), 4He (LETinfinity = 6 keV/micrometer), 12C (LETinfinity = 80 keV/micrometer), 20Ne (LETinfinity = 150 keV/micrometer), 56Fe (LETinfinity = 180 keV/micrometer), and 40Ar (LETinfinity = 650 keV/micrometer). Animals receiving particle radiation were exposed in an extended Bragg peak region except for iron where the plateau region was used. The zones measured in the olfactory bulb were 1) the external plexiform layer (zone) and 2) an internal region consisting of the granule cells, internal plexiform layer, and layer of mitral cells. These studies indicated that volume changes did indeed occur, not only in absolute terms but also when expressed as the ratio of the structures to each other and to the bulb as a whole. Although this study is exploratory in character, the data obtained may nevertheless contribute to a determination of risk factors due to late effects from HZE articles.

The role of repair in the survival of mammalian cells from heavy ion irradiation: approximation to the ideal case of target theory.

Theories of cellular radiation sensitivity that preclude a significant role for cellular repair processes in the final biological expression of cellular damage induced by ionizing radiation are unsound. Experiments are discussed here in which the cell-cycle dependency of the repair deficiency of the S/S variant, of the L5178Y murine leukemic lymphoblast was examined by treatment with the heavy ions, 20Ne, 28Si, 40Ar, 56Fe and 93Nb. Evidence from those studies, which will be described in detail elsewhere, provide support for the notion that as the linear energy transfer (LET infinity) of the incident radiation increases the ability of the S/S cell to repair radiation damage decreases until effectively it is eliminated around 500 keV/micrometer. In the region of the latter LET infinity value, the behavior of the S/S cell approximates the ideal case of target theory where post-irradiation metabolism (repair) does not influence cell survival. The expression of this phenomenon among different cell types and tissues will depend upon the actual repair systems involved and other considerations.

Use of primary cell cultures to measure the late effects in the skins of rhesus monkeys irradiated with protons.

Previous pilot investigations of the uses of primary cell cultures to study late damage in stem cells of the skin of the New Zealand white (NZW) rabbit and the rhesus monkey, have been extended to individual monkeys exposed to 55 MeV protons. Protons of this energy have a larger range in tissue of (approximately 2.6 cm) than the 32 MeV protons (approximately 0.9 cm) to which the animals in our earlier studies had been exposed. Although the primary emphases in the current studies were improvement and simplification in the techniques and logistics of transportation of biopsies to a central analytical facility, comparison of the quantitative measurements obtained thus far for survival of stem cells in the skins from animals irradiated 21 years ago reveals that the effects of both proton energies are similar.

Cataractogenic potential of ionizing radiations in animal models that simulate man.

Aspects of experiments on radiation-induced lenticular opacification during the life spans of two animal models, the New Zealand white rabbit and the rhesus monkey, are compared and contrasted with published results from a life span study of another animal model, the beagle dog, and the most recent data from the ongoing study of the survivors from radiation exposure at Hiroshima and Nagasaki. An important connection among the three animal studies is that all the measurements of cataract indices were made by one of the authors (A.C.L.), so variation form personal subjectivity was reduced to a minimum. The primary objective of the rabbit experiments (radiations involved: 56Fe, 40Ar and 20Ne ions and 60Co gamma photons) is an evaluation of hazards to astronauts from galactic particulate radiations. An analogous evaluation of hazards from solar flares during space flight is being made with monkeys exposed to 32, 55, 138 and 400 MeV protons. Conclusions are drawn about the proper use of animal models to simulate radiation responses in man and the levels of radiation-induced lenticular opacification that pose risks to man in space.

Late cataractogenesis caused by particulate radiations and photons in long-lived mammalian species.

Radiation cataractogenesis induced by small acute doses of particulate radiations and photons in the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), the beagle dog (Canis familiaris) and the rhesus monkey (Macaca mulatta) is discussed in the context of the use of animal models to assess the radiation hazards faced by humans during lengthy sojourns in deep space. Attention is paid to: 1) the importance of lifespan studies with long-lived species--the above animals have median lifespans in captivity of 5-7, 13-14 and approximately 25 years, respectively; 2) the magnitudes of possible dose thresholds for cataractogenesis from sparsely ionizing radiations and the modifications of those thresholds by the late degenerative phase of the phenomenon.

Late effects from particulate radiations in primate and rabbit tissues.

Optic tissues in groups of New Zealand white rabbits were irradiated locally at different stages throughout the median life span of the species with a single dose (9 Gy) of 425 MeV/amu Ne ions (LET infinity approximately 30 keV/micrometer) and then inspected routinely for the progression of radiation cataracts. The level of early cataracts was found to be highest in the youngest group of animals irradiated (8 weeks old), but both the onset of late cataracts and loss of vision occurred earlier when animals were irradiated during the second half of the median life span. This age response can have serious implications in terms of space radiation hazards to man. Rhesus monkeys that had been subjected to whole-body skin irradiation (2.8 and 5.6 Gy) by 32 MeV protons (range in tissue approximately 1 cm) some twenty years previously were analysed for radiation damage by the propagation of skin fibroblasts in primary cultures. Such propagation from skin biopsies in MEM-alpha medium (serial cultivation) or in supplemented Ham's F-10 medium (cultivation without dilution) revealed late damage in the stem (precursor) cells of the skins of the animals. The proton fluxes employed in this experiment are representative of those occurring in major solar flares.

Late cataractogenesis in primates and lagomorphs after exposure to particulate radiations.

Rhesus monkeys that were exposed in 1969, at the age of approximately 2 years, to low doses of "mixed-energy" protons (10- and 110-MeV) are exhibiting progressive (degenerative) lenticular changes. We have conducted regular examinations of this group of monkeys for cataractogenic development since 1987, i.e., 18 years after irradiation, and the animals began to show enhanced degrees of lenticular opacification two years later. The lenses of age-matched controls (median lifespan in captivity approximately 24 years) continue to exhibit much lower levels of opacification (senile cataracts). Trends in the new data are consistent with the cataractogenic patterns observed for other groups of monkeys that were exposed at similar ages in 1964 and 1965 to protons of different energies, and which we began to monitor only 20-21 years later. Therefore, the new information from the mixed-energy group of monkeys provides insight into the development of late cataractogenic sequelae in the other groups of animals during the 2-3 years before we began to measure them. Comparisons are also made here among recent results from the different groups of primates and from New Zealand white (NZW) rabbits that were exposed when young to 56Fe ions and monitored continuously thereafter. This is done because analogous expression of radiation-induced degenerative cataractogenesis also occurs late in the lifespan of the lagomorphs (control median lifespan in captivity approximately 5-7 years), but in this case the cataractogenic profile has been documented through most of the post-irradiation lifespan.

Cataractogenesis from high-LET radiation and the Casarett model.

Space radiations, especially heavy ions, constitute significant hazards to astronauts. These hazards will increase as space missions lengthen. Moreover, the dangers to astronauts will be enhanced by the persistence, or even the progression, of biological damage throughout their subsequent life spans. To assist in the assessment of risks to astronauts, we are investigating the long-term effects of heavy ions on specific animal tissues. In one study, the eyes of rabbits of various ages were exposed to a single dose of Bragg plateau 20Ne ions (LET infinity approximately equals 30 keV/micrometer). The development of cataracts has shown a pronounced age-related response during the first year after irradiation, and will be followed for two more years. In other studies, mice were exposed to single or fractionated doses of 12C ions (4-cm spread-out Bragg peak; dose-averaged LET infinity = 70-80 keV/micrometer) or 60Co gamma-photons (LET infinity = 0.3 keV/micrometer). Measurements of the frequency of posterior lens opacification have shown that the tissue sparing observed with dose fractionation of gamma-photons was absent when 12C-ion doses were fractionated. Development of posterior lens cataracts was also followed for long periods (up to 21 months) in mice exposed to single doses of Bragg plateau HZE particles (40Ar, 20Ne and 12C ions: LET infinity approximately equals 100, 30 and 10 keV/micrometer, respectively) or 225 kVp X-rays. Based on average cataract levels at the different observation times, the RBE's (RBE = relative biological effectiveness) for the ions were circa 5, 3 and 1-2, respectively, over the range of doses used (0.05-0.9 Gy). Investigations of cataractogenesis are useful for exploring the model of radiation damage proposed by Casarett and by Rubin and Casarett with a tissue not connected directly to the vasculature.

Late skin damage in rabbits and monkeys after exposure to particulate radiations.

Skin biopsies were taken from the central regions of the ears of New Zealand white rabbits following localized exposure of one ear of each rabbit to 530 MeV/amu Ar or 365 MeV/amu Ne ions. The unirradiated ears served as controls. Biopsies were taken also from the chests and inner thighs of rhesus monkeys after whole-body exposure to 32 MeV protons and from unirradiated control animals. The linear energy transfers (LET infinity's) for the radiations were 90 +/- 5, 35 +/- 3, and approximately 1.2 keV/micrometer, respectively. In the rabbit studies, explants were removed with a 2 mm diameter dermal punch at post-irradiation times up to five years after exposure. Similar volumes of monkey tissue were taken from skin samples excised surgically 16-18 years following proton irradiation. Fibroblast cultures were initiated from the explants and were propagated in vitro until terminal senescence (cessation of cell division) occurred. Cultures from irradiated tissue exhibited decreases in doubling potential that were dependent on radiation dose and LET infinity and seemed to reflect damage to stem cell populations. The implications of these results for astronauts exposed to heavy ions and/or protons in space include possible manifestations of residual effects in the skin many years after exposure (e.g. unsatisfactory responses to trauma or surgery).

Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.