Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study

Background

Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART.

Methods and Findings

We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting.

Conclusions

Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care.     

Post-Prandial Protein Handling: You Are What You Just Ate

Background

Protein turnover in skeletal muscle tissue is highly responsive to nutrient intake in healthy adults.

Objective

To provide a comprehensive overview of post-prandial protein handling, ranging from dietary protein digestion and amino acid absorption, the uptake of dietary protein derived amino acids over the leg, the post-prandial stimulation of muscle protein synthesis rates, to the incorporation of dietary protein derived amino acids in de novo muscle protein.

Design

12 healthy young males ingested 20 g intrinsically [1-¹³C]-phenylalanine labeled protein. In addition, primed continuous L-[ring-²H₅]-phenylalanine, L-[ring-²H₂]-tyrosine, and L-[1-¹³C]-leucine infusions were applied, with frequent collection of arterial and venous blood samples, and muscle biopsies throughout a 5 h post-prandial period. Dietary protein digestion, amino acid absorption, splanchnic amino acid extraction, amino acid uptake over the leg, and subsequent muscle protein synthesis were measured within a single in vivo human experiment.

Results

55.3±2.7% of the protein-derived phenylalanine was released in the circulation during the 5 h post-prandial period. The post-prandial rise in plasma essential amino acid availability improved leg muscle protein balance (from -291±72 to 103±66 μM·min^-1·100 mL leg volume^-1; P<0.001). Muscle protein synthesis rates increased significantly following protein ingestion (0.029±0.002 vs 0.044±0.004%·h^-1 based upon the muscle protein bound L-[ring-²H₅]-phenylalanine enrichments (P<0.01)), with substantial incorporation of dietary protein derived L-[1-¹³C]-phenylalanine into de novo muscle protein (from 0 to 0.0201±0.0025 MPE).

Conclusion

Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance. About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis.

Trial Registration

trialregister.nl 3638     

Documenting Differences between Early Stone Age Flake Production Systems: An Experimental Model and Archaeological Verification

This study investigates morphological differences between flakes produced via “core and flake” technologies and those resulting from bifacial shaping strategies. We investigate systematic variation between two technological groups of flakes using experimentally produced assemblages, and then apply the experimental model to the Cutting 10 Mid -Pleistocene archaeological collection from Elandsfontein, South Africa. We argue that a specific set of independent variables—and their interactions—including external platform angle, platform depth, measures of thickness variance and flake curvature should distinguish between these two technological groups. The role of these variables in technological group separation was further investigated using the Generalized Linear Model as well as Linear Discriminant Analysis. The Discriminant model was used to classify archaeological flakes from the Cutting 10 locality in terms of their probability of association, within either experimentally developed technological group. The results indicate that the selected independent variables play a central role in separating core and flake from bifacial technologies. Thickness evenness and curvature had the greatest effect sizes in both the Generalized Linear and Discriminant models. Interestingly the interaction between thickness evenness and platform depth was significant and played an important role in influencing technological group membership. The identified interaction emphasizes the complexity in attempting to distinguish flake production strategies based on flake morphological attributes. The results of the discriminant function analysis demonstrate that the majority of flakes at the Cutting 10 locality were not associated with the production of the numerous Large Cutting Tools found at the site, which corresponds with previous suggestions regarding technological behaviors reflected in this assemblage.     

Using an in vitro cytotoxicity assay to aid in compound selection for in vivo safety studies

Recent publications have demonstrated that using calculated physiochemical properties can help in the design of compounds that have a decreased risk of significant findings in rodent toxicology studies. In this Letter, we extend this concept and incorporate results from a high throughput cytotoxicity assay to help the drug discovery community select compounds for progression into in vivo studies. The results are presented in an easily interpretable odds ratio so that teams can readily compare compounds and progress potential clinical candidates to the necessary rodent in vivo studies.     

On the 13C/12C isotopic signal of day and night respiration at the mesocosm level

While there is currently intense effort to examine the ¹³C signal of CO₂ evolved in the dark, less is known on the isotope composition of day‐respired CO₂. This lack of knowledge stems from technical difficulties to measure the pure respiratory isotopic signal: day respiration is mixed up with photorespiration, and there is no obvious way to separate photosynthetic fractionation (pure c_i/c_a effect) from respiratory effect (production of CO₂ with a different δ¹³C value from that of net‐fixed CO₂) at the ecosystem level. Here, we took advantage of new simple equations, and applied them to sunflower canopies grown under low and high [CO₂]. We show that whole mesocosm‐respired CO₂ is slightly ¹³C depleted in the light at the mesocosm level (by 0.2–0.8‰), while it is slightly ¹³C enriched in darkness (by 1.5–3.2‰). The turnover of the respiratory carbon pool after labelling appears similar in the light and in the dark, and accordingly, a hierarchical clustering analysis shows a close correlation between the ¹³C abundance in day‐ and night‐evolved CO₂. We conclude that the carbon source for respiration is similar in the dark and in the light, but the metabolic pathways associated with CO₂ production may change, thereby explaining the different ¹²C/¹³C respiratory fractionations in the light and in the dark.     

Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry

Background

In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.

Methods

Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.

Results

49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM. With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia. In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers. The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3). 46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.

Conclusions

In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.