Adherence to Pre-exposure Prophylaxis in Black Men Who Have Sex with Men and Transgender Women in a Community Setting in Harlem, NY.

While oral pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention, consistent use is necessary to achieve its intended impact. We compared effectiveness of enhanced PrEP (enPrEP) adherence support to standard of care (sPrEP) among Black MSM and TGW attending a community clinic in Harlem, NY. EnPrEP included peer navigation, in-person/online support groups, and SMS messages. Self-reported adherence over previous 30 days, collected in quarterly interviews, was defined as ≥ 57%. Crude and adjusted analyses examined factors associated with adherence. A total of 204 participants were enrolled and randomized; 35% were lost to follow-up. PrEP adherence was 30% at 12-months; no intervention effect was observed (p = 0.69). Multivariable regression analysis found that lower adherence was associated with low education and depressive symptoms. We found that an enhanced adherence intervention did not improve PrEP adherence. Findings point to the need for innovative methods to improve PrEP adherence among Black MSM and TGW.Clinical Trial Registration NCT02167386, June 19, 2014.

A seafood risk tool for assessing and mitigating chemical and pathogen hazards in the aquaculture supply chain.

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets.

Radical maxillectomy as a successful treatment for gunshot-induced maxillary and nasal cavity trauma in a dog.

OBJECTIVE: To report the successful treatment of gunshot-induced maxillary and nasal cavity damage with total maxillectomy in a two-year-old Labrador retriever dog. METHODS: Radical maxillectomy was performed on highly comminuted maxillary and nasal cavity fractures resulting from gunshot trauma. The procedure was performed to remove the damaged region and reconstruct the remaining tissue. RESULTS: Treatment of the fractures by total maxillectomy was successful in reconstruction of the remaining structures following debridement and in re-establishing return to normal activities and high owner satisfaction. CLINICAL SIGNIFICANCE: The outcome in this case suggests that severe maxillary and nasal cavity trauma in other dogs may be treated with radical maxillectomy given appropriate patient and owner selection.

Adherence to treatment for latent tuberculosis infection: systematic review of studies in the US and Canada.

BACKGROUND: There is renewed attention to the critical role of successfully treating latent tuberculosis infection (LTBI) in reducing the overall impact of tuberculosis (TB). However, levels of treatment adherence are consistently low in industrialized countries such as the United States and Canada. OBJECTIVE: A systematic review of studies in the US and Canada was undertaken to analyze measurement of adherence to treatment of LTBI (TLTBI), TLTBI completion rates, predictors of TLTBI adherence and TLTBI adherence interventions. METHODS: PUBMED, MEDLINE and PsycINFO electronic databases were searched for quantitative studies published between 1997 and 2007. Full texts of articles were reviewed for data abstraction and studies were critically examined for their methodology and rigor. The present review presents outcomes from 78 studies. RESULTS: Adherence and completion rates of TLTBI are suboptimal across high-risk groups, regardless of regimen. Associations between adherence and patient factors, clinic facilities or treatment characteristics were found to be inconsistent across studies. Several adherence interventions have been developed to improve TLTBI adherence in the US and Canada; however, no single intervention has shown consistent effectiveness. CONCLUSION: LTBI must be effectively treated if the goal of TB elimination is to be realized. Consistently employing tools for measuring and improving adherence is fundamental. Identifying barriers to adherence and treatment completion will facilitate the development of effective, appropriate interventions. A 'one-size-fits-all' approach to treatment for TLTBI adherence is not likely to succeed across all settings. Innovative approaches can inspire future interventions and suggest solutions for the current problems facing LTBI programs and their patients.

Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat.

Previous studies are in conflict over the effect of infusing mixed fibrinogen-fibrin degradation products on fibrinogen synthesis, as determined by changes in fibrinogen concentration or by incorporation of labeled amino acids into fibrinogen. We have injected purified homologous fragments D1 and E into rats and measured their fibrinogen and albumin synthetic rates by the [14C]carbonate technique, a method that provides quantitative estimates of hepatic secretory protein synthesis. Fibrinogen fractional synthetic rates were increased 2.5 times in animals injected with fragment D1, compared with saline-injected controls. No increase were observed in fragment E-injected animals. Neither fragment produced changes in albumin synthesis. Fragment D increased plasma fibrinogen concentration, but did not raise plasma haptoglobin levels. These results suggest that fragment D is a regulator of fibrinogen synthesis.

Comparison of procoagulant activities in extracts of normal and malignant human tissue.

Cancer procoagulant A (CPA) was originally described in extracts of tumor tissue, but whether this represented a quantitative and/or a qualitative difference from procoagulant activity in normal tissue extracts was not clear. Procoagulant activity was quantitated in extracts of 12 matched normal and malignant human tissue samples from the large intestine, breast, lung, and kidney. The specific activity of procoagulants in the tumor extracts was not greater than that in the extracts of normal tissue. Two enzymatic characteristics of CPA that distinguish it from tissue thromboplastin are its inhibition by diisopropylfluorophosphate (DFP) and its lack of dependence on factor VII. These specific tests were used to evaluate qualitative differences between procoagulants from normal and malignant intestinal tissues. In the paired normal and malignant tissue extracts, all tumor samples were inhibited by DFP and were active in factor VII-depleted bovine plasma (F7D-BP). In contrast, the extracts of normal tissue were insensitive to DFP and, except for one extract, were inactive in F7D-BP. Four of 9 other tumor extracts (44%) were positive for both of these tests for CPA, whereas the other 5 extracts were positive for only one of the two tests. The results suggest that extracts of normal and malignant tissues contained similar levels of procoagulant. However, malignant tissue contained a procoagulant enzymatically different from normal tissue thromboplastin. Furthermore, most of the malignant tissue extracts seemed to contain little or no thromboplastin.

Further studies on platelet serotonin transporter binding in depression.

OBJECTIVE: There is an impressive literature implicating abnormalities in serotonergic neural systems in depression. Many investigators, but not all, have reported low numbers of platelet and brain serotonin (5-HT) transporter sites in drug-free depressed patients. In the present study the authors sought to determine whether the low platelet 5-HT transporter binding in depressed patients is due to previous antidepressant drug exposure. In addition, the binding of both [3H]imipramine and the more specific ligand [3H]paroxetine to the platelet 5-HT transporter was compared in drug-free depressed patients and age- and sex-matched normal comparison subjects. METHOD: In the first experiment blood samples were obtained from 12 depressed patients who had never received antidepressant drugs and 12 normal comparison subjects, and platelet 5-HT transporter binding was measured by using [3H]imipramine. In the second experiment blood samples were obtained from 28 drug-free depressed patients and 28 age- and sex-matched comparison subjects, and platelet 5-HT transporter binding was assessed by using both [3H]imipramine and [3H]paroxetine. RESULTS: In the first experiment the never-medicated depressed patients exhibited fewer platelet [3H]imipramine binding sites than did the comparison subjects. In the second experiment the drug-free depressed patients had fewer platelet binding sites for both [3H]imipramine and [3H]paroxetine than did the comparison subjects. CONCLUSIONS: The low number of platelet [3H]imipramine binding sites does not appear to be due to prior antidepressant drug exposure. The Bmax of platelet binding sites for both [3H]imipramine and [3H]paroxetine, ligands used to measure 5-HT transporter binding, is abnormally low in depressed patients.

Differences in judgments of learning difficulty.

Academically successful and less successful fifth graders were asked to make judgments about the ease of understanding and remembering various sentences and were given the opportunity to attempt to remember some of them before being asked to judge new sets of sentences. The results of the first experiment indicate that, at the beginning of the experiment, the successful students were much more likely than their less successful peers to realize that sentences expressing arbitrary relationships were more difficult to remember. These differences became even greater after students were given the opportunity to attempt to remember some of the sentences they had judged initially. The memory performance of the successful students also improved as they became more familiar with the experimental task, but the performance of the less successful students did not. The results of the second experiment showed that less successful students who had received appropriate training were able to use information about the arbitrariness of relationships as the basis for their judgments of learning difficulty. The training also facilitated their ability to remember. Implications of these findings are discussed.

Biocompatibility of diamond-like carbon coating.

Diamond-like carbon coating is an inert, impervious hydrocarbon coating with properties suitable for use in the biomedical field, particularly in orthopaedic implants. Mouse peritoneal macrophages and mouse fibroblasts were grown on tissue culture plates treated with diamond-like carbon and the biocompatibility assessed both biochemically and morphologically. This investigation showed that diamond-like carbon coating caused no adverse effects on cells in culture and therefore merits further investigation as a coating for biomedical use.

Marrow biopsy and survival in multiple myeloma.

Pretreatment posterior iliac crest bone marrow biopsies were obtained from 26 multiple myeloma patients. Biopsies were processed in methacrylate. The percentage of myeloma tissue, myeloid tissue, and fat was estimated in each biopsy. In 20 patients who died there was a positive correlation between the percent of myeloid tissue in posterior iliac crest biopsies and survival time (r = 0.47, P less than 0.025), but no correlation could be demonstrated between percentage of myeloma tissue and survival time. The ratio of percentage of myeloid tissue to percentage of myeloma tissue also was related to survival. Six deceased patients with ratios greater than one had a median survival of 4.4 years, compared with 1.8 years in 12 deceased patients with ratios less than one. These medians differ significantly (P less than 0.05). Seven patients also had simultaneous biopsies of the posterior iliac crest and either or both the greater trochanter and the proximal tibia. All five greater trochanter biopsies showed extension of both myeloma tissue and myeloid tissue into the proximal appendicular skeleton.

Chimerism in grapevines: implications for cultivar identity, ancestry and genetic improvement.

In the course of DNA profiling of grapevine cultivars using microsatellite loci we have occasionally observed more than two alleles at a locus in some individuals and have identified periclinal chimerism as the source of such anomalies. This phenomenon in long-lived clonally propagated crops, such as grapevine, which contains historically ancient cultivars, may have a role in clonal differences and affect cultivar identification and pedigree analysis. Here we show that when the two cell layers of a periclinal chimera, Pinot Meunier, are separated by passage through somatic embryogenesis the regenerated plants not only have distinct DNA profiles which are different from those of the parent plant but also have novel phenotypes. Recovery of these phenotypes indicates that additional genetic differences can exist between the two cell layers and that the Pinot Meunier phenotype is due to the interaction of genetically distinct cell layers. It appears that grapevine chimerism can not only modify phenotype but can also impact on grapevine improvement as both genetic transformation and conventional breeding strategies separate mutations in the L1 and L2 cell layers.

Halothane-induced alteration in the fluidity of rat brain synaptosomal membranes and its relationship to anesthesia.

Concentrations of halothane 1.43% or higher abolished the pain response and induced anesthesia. Halothane increased membrane fluidity of synaptosomes and microsomes both at non-anesthetic and anesthetic concentrations. Changes in fluidity in synaptosomes did not return to control levels even after the animals recovered from anesthesia. Alteration in membrane fluidity by halothane is a non-selective effect and may not play a definitive role in anesthesia.

Fibrin- and fibrinogen-related antigens in patients with venous disease and venous ulceration.

Abnormalities in systemic fibrinolysis have been implicated in the pathogenesis of venous ulceration. Patients with venous disease have a prolonged euglobulin lysis time and elevated plasma fibrinogen levels, yet little is known about the metabolism of fibrinogen and fibrin in such patients. In this study, we have used a technique that involves electrophoresis and densitometric analysis of captured fibrin-related antigens to measure the concentration and proportions of the individual fibrin and fibrinogen degradation products in patients with venous disease of the lower extremity. As a group, patients with venous disease had markedly elevated levels of total fibrin-related antigen and D-dimer, the terminal degradation product of cross-linked fibrin. Levels of D-monomer, the breakdown product of fibrinogen and non-cross-linked fibrin monomer, and a measure of fibrinogenolysis were normal in all patients. In patients with ulcers, the levels of D-dimer were disproportionately higher than expected from fibrin monomer levels. On an individual basis, significant elevations of D-dimer were present in six (55%) of the 11 patients with venous disease with ulcers and in three (43%) of the seven patients with venous disease without ulcers. We conclude that patients with venous disease have uniform evidence for enhanced fibrin formation, as evidenced by elevated levels of total fibrin-related antigen and D-dimer. This is regardless of whether the venous disease is accompanied by ulceration.

Halothane alters electrical activity and calcium dynamics in cultured mouse cortical, spinal cord, and dorsal root ganglion neurons.

Halothane inhibits neural plasma membrane Ca(2+)-ATPase, a pump that ejects Ca2+ from the cell after influx through voltage- or ligand-activated channels. Intracellular microelectrode recordings in mouse embryonic cortical and spinal cord neurons showed that halothane and eosin, a pump inhibitor, prolonged repolarization associated with spontaneous bursts of depolarization. These agents also prolonged the repolarization phases of electrically induced action potentials and of capsaicin-mediated Ca(2+)-dependent depolarization in mouse adult dorsal root ganglion neurons. In keeping with these findings, confocal microfluorimetry showed that halothane delayed clearance of intracellular Ca2+ accumulated by N-methyl-D-aspartate stimulation of single neurons.

Alcohol pretreatment alters the metabolic pattern and accelerates cocaine metabolism in pigs.

We investigated whether alcohol pretreatment would affect the disposition and metabolic pattern of intravenously (i.v.) administered cocaine in pigs. Six pigs (Group A) received alcohol (1 g/kg/day) and six pigs (control; Group D) received an equal volume of isocaloric dextrose 44% in water for 10 days via an intragastric tube. On day 11, arterial samples were taken for five hours following an intravenous administration of cocaine hydrochloride (4 mg/kg). Plasma concentrations of cocaine and its major metabolites were analyzed by HPLC method. Significant decrease in plasma half-life (10 +/- 1.2 vs. 18.7 +/- 1.4 min), and significant increases in apparent volume of distribution (73 +/- 6 vs. 51 +/- 31) and clearance (5.37 +/- 0.6 vs. 1.82 +/- 0.1 l/min) were seen in alcohol pretreated pigs as compared with control pigs (P < 0.05). Significant increases in plasma concentrations of benzoylecgonine (P < 0.05), and insignificant differences in ecgonine methyl ester and norcocaine levels were seen between the two groups. Neither ecgonine nor cocaethylene was detected in the blood samples. Our data show that alcohol administration for ten days accelerated the elimination of i.v. administered cocaine and altered its metabolic pattern in pigs.

Nitrous oxide and xenon enhance phospholipid-N-methylation in rat brain synaptic plasma membranes.

Halothane and isoflurane increase the rate of phospholipid methylation (PLM) in rat brain synaptosomal membranes, a process linked to the coupling of neuronal excitation to neurotransmitter release. In contrast, synaptic plasma membrane (SPM) Ca2+ ATPase (PMCA) pumping is reduced by exposure to halothane, isoflurane, xenon and nitrous oxide (N2O). To examine further the relationship between PLM, PMCA and anesthetic action, we investigated the effect of clinically relevant concentrations of two less potent anesthetic gases, N2O and xenon, on PLM in SPM. Biochemical assays were performed on SPM exposed to 1.3 MAC of N2O (2 atm), 1.3 MAC of xenon (1.23 atm) or an equivalent pressure of helium for control. N2O or xenon exposure increased PLM to 115% or 113%, respectively, of helium control (p < 0.02). Similar exposures to N2O or xenon depressed PMCA activity to 78% and 85% of control (p < 0.05). Observations that PLM and PMCA are both altered by a wide variety of inhalation anesthetic agents at clinically relevant partial pressures lend support to a possible involvement and interaction of these processes in anesthetic action.

Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in spontaneously hypertensive rats: association with reduced anesthetic requirements.

We have recently reported that plasma membrane Ca(2+)-ATPase (PMCA) pumping activity in rat brain synaptic plasma membranes (SPM) was reduced by in vitro or prior in vivo exposure to inhalation anesthetics (IA). In addition, rats with streptozocin-induced diabetes were found to have diminished brain synaptic PMCA pumping and a decrease in the partial pressures of several IA required to prevent movement in response to stimulation, defined as the minimum effective dose or MED. Diminished PMCA activity in erythrocytes of spontaneously hypertensive rats (SHR) has been noted. Because PMCA is ubiquitous, it seemed possible that PMCA pumping might be decreased in the brain of SHR and perhaps associated with decreased IA requirement. Eighteen SHR and 18 control, normotensive Wistar-Kyoto rats (WKY) were studied. PMCA activity was assessed by measurement of Ca2+ uptake into synaptic plasma membrane vesicles prepared from cerebrum and diencephalon-mesencephalon (D-M) in WKY and SHR. Ca2+ pumping was significantly less in SHR than in WKY, 85% of control in the cerebrum and 90% in the D-M (p < 0.01). The MEDs for halothane, isoflurane and desflurane were also lower in SHR than in WKY, 91%, 90% and 89%, respectively, of control (p < 0.05). Thus, an animal model of primary hypertension (SHR) manifested diminished brain synaptic PMCA activity and reduced MED for several volatile anesthetics. These findings provide further evidence for a role for PMCA in anesthetic action.

Lack of effect of flurothyl, a non-anesthetic fluorinated ether, on rat brain synaptic plasma membrane calcium-ATPase.

Plasma membrane Ca2+-ATPase (PMCA), a regulator of intracellular calcium, is inhibited by volatile anesthetics and by xenon and nitrous oxide. Response of a cellular system to anesthetics, particularly to volatile agents, raises the question of non-specific, even toxic, side effects unrelated to anesthetic action. Compounds with chemical and physical properties similar to halogenated anesthetics, but which lack anesthetic effect, have been used to address this question. We have compared the effects of halothane and flurothyl, a non-anesthetic fluorinated ether, on PMCA Ca2+ transport across isolated brain synaptic plasma membranes (SPM). Flurothyl, at concentrations predicted by the Meyer-Overton curve to range from 0.4 to 2.6 MAC (minimum alveolar concentration), had no significant on PMCA activity. In contrast halothane, 1.3 MAC, reduced Ca2+ transport 30 to 40%. These findings provide further evidence for a specific effect of inhalation anesthetics on neuronal plasma membrane Ca2+-ATPase.

Inhibition of plasma membrane Ca(2+)-ATPase pump activity in cultured C6 glioma cells by halothane and xenon.

We have compared the effect of two inhalational anesthetics, halothane and xenon, on Ca(2+)-ATPase (PMCA) pumping activity in plasma membrane vesicles prepared from cultured rat C6 glioma cells. Halothane, at concentrations ranging from 0.5 to 1.75 vol% (equivalent to 0.5 to 1.6 MAC), significantly inhibited Ca2+ uptake (transport) by plasma membrane vesicles in a dose-related fashion. Xenon, at partial pressures ranging from 0.5 to 1.5 atm (equivalent to 0.5 to 1.6 MAC), similarly inhibited PMCA pumping activity. Additive effects on suppression of PMCA pump activity were observed when C6 cell plasma membrane vesicles were exposed to increasing partial pressures of xenon in the presence of halothane (1 vol%). Halothane also inhibited PMCA pumping in cells from two other lines of neural origin, B104 (rat neuroblastoma) and PC12 (rat pheochromocytoma). Studies described in this report support the thesis that PMCA in cells of neural origin is inhibited by quite different inhalational anesthetics at clinically relevant concentrations.

Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in rats with streptozocin-induced diabetes: association with reduced anesthetic requirements.

Recent evidence suggests that chronic hyperglycemia may inhibit plasma membrane Ca(2+)-ATPase (PMCA) in cells from several tissues. Inhalational anesthetics (IA) can inhibit brain synaptic PMCA activity. We proposed that diabetic rats may manifest chronic inhibition of brain synaptic PMCA and thus provide a model for testing the hypothesis that synaptic PMCA plays a key role in IA pharmacodynamics. Ca2+ pumping activity of PMCA was measured in cerebral synaptic plasma membrane (SPM) vesicles prepared from rats with streptozocin (STZ)-induced diabetes and from control, normoglycemic rats. Dose requirements for halothane and xenon were estimated in treated and untreated rats. Brain PMCA activity in hyperglycemic rats was depressed by about 8.4%, compared to controls. In vitro glycation also caused a significant decrease in PMCA pumping activity. Halothane requirement for STZ-hyperglycemic rats was dramatically reduced to about 65% of control. Xenon requirement was also significantly reduced, to 88% of control. Correlation of IA dose with percent glycated hemoglobin for each rat revealed a strong association between reduced requirements for halothane or xenon and increased protein glycation. These results indicate that inhibition of brain synaptic PMCA in chronically hyperglycemic rats is associated with a significant reduction in IA requirement.