Exploring Clinical Remission in Moderate Asthma - Perspectives from Asia, the Middle East, and South America.

INTRODUCTION: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. METHODS: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. RESULTS: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. CONCLUSIONS: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

GINA Implementation Improves Asthma Symptoms Control and Lung Function: A Five-Year Real-World Follow-Up Study.

Symptoms control remains challenging for most patients with asthma. This study was conducted to evaluate the level of asthma symptoms control and lung function over 5 years of GINA (Global INitiative for Asthma) implementation. We included all patients with asthma who had been managed following GINA recommendations at the Asthma and COPD Outpatient Care Unit (ACOCU) of the University Medical Center in Ho Chi Minh City, Vietnam from October 2006 to October 2016. Of 1388 patients with asthma managed following GINA recommendations, the proportion of patients with well-controlled asthma significantly improved from 2.6% at baseline to 66.8% at month 3, 64.8% at year 1, 59.6% at year 2, 58.6% at year 3, 57.7% at year 4, and 59.5% at year 5 (p < 0.0001 for all comparisons). The proportion of patients with persistent airflow limitation significantly decreased from 26.7% at baseline to 12.6% at year 1 (p < 0.0001), 14.4% at year 2 (p < 0.0001), 15.9% at year 3 (p = 0.0006), 12.7% at year 4 (p = 0.0047), and 12.2% at year 5 (p = 0.0011). In patients with asthma managed according to GINA recommendations, asthma symptoms control and lung function improved after 3 months and the improvement was sustained over 5 years.

The role of depression in secondary HIV transmission among people who inject drugs in Vietnam: A mathematical modeling analysis.

BACKGROUND: Among people who inject drugs (PWID), depression burden is high and may interfere with HIV prevention efforts. Although depression is known to affect injecting behaviors and HIV treatment, its overall impact on HIV transmission has not been quantified. Using mathematical modeling, we sought to estimate secondary HIV transmissions and identify differences by depression among PWID. METHODS: We analyzed longitudinal data from 455 PWID living with HIV in Vietnam during 2009-2013. Using a Bernoulli process model with individual-level viral load and behavioral data from baseline and 6-month follow-up visits, we estimated secondary HIV transmission events from participants to their potentially susceptible injecting partners. To evaluate differences by depression, we compared modeled transmissions per 1,000 PWID across depressive symptom categories (severe, mild, or no symptoms) in the three months before each visit. RESULTS: We estimated a median of 41.2 (2.5th, 97.5th percentiles: 33.2-49.2) secondary transmissions from all reported acts of sharing injection equipment with 833 injecting partners in the three months before baseline. Nearly half (41%) of modeled transmissions arose from fewer than 5% of participants in that period. Modeled transmissions per 1,000 PWID in that period were highest for severe depressive symptoms (100.4, 80.6-120.2) vs. mild (87.0, 68.2-109.4) or no symptoms (78.9, 63.4-94.1). Transmission estimates fell to near-zero at the 6-month visit. CONCLUSIONS: Secondary transmissions were predicted to increase with depression severity, although most arose from a small number of participants. Our findings suggest that effective depression interventions could have the important added benefit of reducing HIV transmission among PWID.

Stentectomy for LAD "full metal jacket" with in-stent restenosis: How to do it.

We report our technique for the surgical revascularization of symptomatic severe in-stent restenosis of a "full metal jacket" (≥60 mm overlapping stents) of the left anterior descending coronary artery without suitable distal targets: on-pump cardioplegic-arrest stent removal (stentectomy) with endarterectomy and skeletonized left internal mammary artery onlay patch reconstruction. We also describe our follow-up protocol, including antiplatelet/anticoagulation and angiography. With proper patient selection, multidisciplinary collaboration, and surgical expertise, this advanced coronary procedure can be beneficial to a growing population of patients otherwise deemed to be untreatable.

Mapping the potential aggregation values of ecotourism landscapes from stakeholder survey, structural equation modeling and GIS: Case study of Moc Chau site, Vietnam.

The primary aim of this study is to propose a potential landscape value assessment from different dimensions rather than the traditional approach of a composite indicator. The method used in this study is the combination of data collection from stakeholder survey, score measurement for landscape value dimensions using Structural Equation Modeling (SEM), and spatial representation with the support of Geographic Information System (GIS). From a large-scale (n = 400) investigation in the Moc Chau district, the statistical data extracted from the survey provides input data for the score determination process. SEM analysis shows that each landscape site has 11 determinants influencing the landscape value assessment. Using the RMSE comparison (for validation) with different interpolation methods, the ordinary kriging method is chosen to model the aggregation landscape value map of Moc Chau District. About 24.97% total area of the study area has great potential for tourism development, being mainly distributed in the center of a high mountainous area. This approach can be used as a model to advocate local and regional assessment and enhance value-based management in other territories in Vietnam and beyond.

Estimating the Effect of Depression on HIV Transmission Risk Behaviors Among People Who Inject Drugs in Vietnam: A Causal Approach.

The burden of depression and HIV is high among people who inject drugs (PWID), yet the effect of depression on transmission risk behaviors is not well understood in this population. Using causal inference methods, we analyzed data from 455 PWID living with HIV in Vietnam 2009-2013. Study visits every 6 months over 2 years measured depressive symptoms in the past week and injecting and sexual behaviors in the prior 3 months. Severe depressive symptoms (vs. mild/no symptoms) increased injection equipment sharing (risk difference [RD] = 3.9 percentage points, 95% CI -1.7, 9.6) but not condomless sex (RD = -1.8, 95% CI -6.4, 2.8) as reported 6 months later. The cross-sectional association with injection equipment sharing at the same visit (RD = 6.2, 95% CI 1.4, 11.0) was stronger than the longitudinal effect. Interventions on depression among PWID may decrease sharing of injection equipment and the corresponding risk of HIV transmission.Clinical trial registration ClinicalTrials.gov NCT01689545.

Depression, antiretroviral therapy initiation, and HIV viral suppression among people who inject drugs in Vietnam.

BACKGROUND: The burden of depression is high among people who inject drugs (PWID) and may contribute to the spread of HIV through poor treatment engagement and persistent viremia. We estimated the effects of depression on antiretroviral therapy (ART) initiation and viral suppression among PWID living with HIV. METHODS: Longitudinal data were collected from 455 PWID living with HIV in Vietnam during 2009-2013. We estimated the 6- and 12-month cumulative incidence of ART initiation and viral suppression, accounting for time-varying confounding, competing events, and missing data. The cumulative incidence difference (CID) contrasted the incidence of each outcome had participants always vs. never experienced severe depressive symptoms across study visits to date. RESULTS: Severe depressive symptoms decreased the cumulative incidence of ART initiation, with CID values comparing always vs. never having severe depressive symptoms of -7.5 percentage points (95% CI: -17.2, 2.2) at 6 months and -7.1 (95% CI: -17.9, 3.7) at 12 months. There was no appreciable difference in the cumulative incidence of viral suppression at 6 months (CID = 0.3, 95% CI: -11.3, 11.9) or 12 months (CID = 2.0, 95% CI: -21.8, 25.8). LIMITATIONS: Discrepancies between the ART initiation and viral suppression outcomes could be due to under-reporting of ART use and missing data on viral load. CONCLUSIONS: Future work probing the seemingly antagonistic effect of depression on treatment uptake - but not viral suppression - will inform the design of interventions promoting HIV clinical outcomes and reducing onward transmission among PWID.

Deep red fluoride dots-in-nanoparticles for high color quality micro white light-emitting diodes.

In this study, a novel nanostructure of fluoride red emitting phosphor is synthesized via soft templates. K2SiF6:Mn4+ nanocrystals in the range of 3-5 nm diameter are found inside the porous K2SiF6:Mn4+ nanoparticle hosts, forming unique dots-in-nanoparticles (d-NPs) structures with controlled optical properties. The porous K2SiF6:Mn4+ d-NPs exhibit a sharp and deep red emission with an excellent quantum yield of ∼95.9%, and ultra-high color purity with the corresponding x and y in the CIE chromaticity coordinates are 0.7102 and 0.2870, respectively. Moreover, this nanophosphor possesses good thermal stability in range of 300 K-500 K, under light excitation of 455 nm. The K2SiF6:Mn4+ d-NPs are covered onto a surface of 100×100 µm2 blue-yellow InxGa1-xN nanowire light-emitting diode (LED) to make warm white LEDs (WLEDs). The fabricated WLEDs present an excellent color rendering index of ∼95.4 and a low correlated color temperature of ∼3649 K. Porous K2SiF6:Mn4+ d-NPs are suggested as a potential red component for high color quality micro WLED applications.

Longitudinal Analysis of Depressive Symptoms, Perceived Social Support, and Alcohol Use among HIV-Infected Men Who Inject Drugs in Northern Vietnam.

Background: Limited research examines depressive symptoms, alcohol use, and social support among HIV-infected people who inject drugs. Objectives: Using longitudinal data, we investigated whether perceived social support moderates the relationship between depressive symptoms and alcohol use among HIV-infected men who inject drugs in Vietnam. Methods: Data were collected from participants (N = 455; mean age 35 years) in a four-arm randomized controlled trial in Thai Nguyen, Vietnam. Data were collected at baseline, 6, 12, 18, and 24 months with 94% retention excluding dead (N = 103) or incarcerated (N = 37) participants. Multilevel growth models were used to assess whether: (1) depressive symptoms predict when risk of alcohol use is elevated (within-person effects); (2) depressive symptoms predict who is at risk for alcohol use (between-person effects); and (3) within- and between-person perceived social support moderates the depressive symptoms-alcohol relationship. Results: Participants reported high but declining levels of depressive symptoms and alcohol use. Participants with higher depressive symptoms drank less on average (B = -0.0819, 95% CI -0.133, -0.0307), but within-person, a given individual was more likely to drink when they were feeling more depressed than usual (B = 0.136, 95% CI 0.0880, 0.185). The positive relationship between within-person depressive symptoms and alcohol use grew stronger at higher levels of within-person perceived social support. Conclusions: HIV-infected men who inject drugs have increased alcohol use when they are experiencing higher depressive symptoms than usual, while those with higher average depressive symptoms over time report less alcohol use. Social support strengthens the positive relationship between within-person depressive symptoms and alcohol use.

Impact of Abstinence and of Reducing Illicit Drug Use Without Abstinence on Human Immunodeficiency Virus Viral Load.

BACKGROUND: Substance use is common among people living with human immunodeficiency virus (PLWH) and a barrier to achieving viral suppression. Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved. METHODS: This was a longitudinal cohort study of PLWH from 7 HIV clinics or 4 clinical studies. We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL. RESULTS: The number of PLWH who were using each drug at baseline ranged from n = 568 (illicit opioids) to n = 4272 (marijuana). Abstinence was associated with higher odds of viral suppression (odds ratio [OR], 1.4-2.2) and lower relative VL (ranging from 21% to 42% by drug) for all 4 drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR, 2.2, 1.6, respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38%, respectively). CONCLUSIONS: Abstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Our findings highlight the impact of reducing substance use, even when abstinence is not achieved, and the potential benefits of medications, behavioral interventions, and harm-reduction interventions.

Depressive Symptoms at HIV Testing and Two-Year All-Cause Mortality Among Men Who Inject Drugs in Vietnam.

People who inject drugs (PWID) with HIV experience an elevated risk of death. A potentially important determinant of survival is the high burden of depression. This study examined the relationship of depressive symptoms at HIV testing with 2-year all-cause mortality among newly diagnosed HIV-positive PWID in Vietnam. At HIV testing, 141 PWID (42%) experienced severe depressive symptoms, and over the 2 years following diagnosis, 82 PWID (24%) died. Controlling for potential confounders, the 2-year risk of death among those with depressive symptoms was 9.7% (95% CI - 1.2, 20.6%) higher than the risk among those without depressive symptoms. This increased risk of mortality for PWID with depressive symptoms was relatively consistent throughout the 2-year period: at 6, 12, and 18 months, the risk difference was 12.6% (5.5-19.7%), 13.9% (4.6-23.2%), and 11.0% (0.9-21.1%), respectively. HIV diagnosis may provide an important opportunity for depression screening and treatment, subsequently improving survival in this key population.Trial registry: ClinicalTrials.gov NCT01689545.

Approaches for creating comparable measures of alcohol use symptoms: Harmonization with eight studies of criminal justice populations.

BACKGROUND: With increasing data archives comprised of studies with similar measurement, optimal methods for data harmonization and measurement scoring are a pressing need. We compare three methods for harmonizing and scoring the AUDIT as administered with minimal variation across 11 samples from eight study sites within the STTR (Seek-Test-Treat-Retain) Research Harmonization Initiative. Descriptive statistics and predictive validity results for cut-scores, sum scores, and Moderated Nonlinear Factor Analysis scores (MNLFA; a psychometric harmonization method) are presented. METHODS: Across the eight study sites, sample sizes ranged from 50 to 2405 and target populations varied based on sampling frame, location, and inclusion/exclusion criteria. The pooled sample included 4667 participants (82% male, 52% Black, 24% White, 13% Hispanic, and 8% Asian/ Pacific Islander; mean age of 38.9 years). Participants completed the AUDIT at baseline in all studies. RESULTS: After logical harmonization of items, we scored the AUDIT using three methods: published cut-scores, sum scores, and MNLFA. We found greater variation, fewer floor effects, and the ability to directly address missing data in MNLFA scores as compared to cut-scores and sum scores. MNLFA scores showed stronger associations with binge drinking and clearer study differences than did other scores. CONCLUSIONS: MNLFA scores are a promising tool for data harmonization and scoring in pooled data analysis. Model complexity with large multi-study applications, however, may require new statistical advances to fully realize the benefits of this approach.

Prevalence and predictors of depressive symptoms among HIV-positive men who inject drugs in Vietnam.

BACKGROUND: HIV infection is common among people who inject drugs (PWID), and HIV-positive PWID may be particularly vulnerable to depression. This study measured the prevalence of depressive symptoms and the factors associated with severe symptoms among 455 HIV-positive PWID in Thai Nguyen, Vietnam. METHODS: We used cross-sectional data from PWID in a randomized controlled trial of an intervention to reduce high-risk injecting and sexual behaviors in Thai Nguyen from 2009-2013. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). We used logistic regression to assess demographic, clinical, and psychosocial predictors of severe depressive symptoms (CES-D≥23) with prevalence odds ratios (POR) and 95% confidence intervals (CI). RESULTS: The prevalence of severe depressive symptoms (CES-D≥23) was 44%. 25% of participants had mild to moderate depressive symptoms (16≤CES-D<23), and 31% experienced no depressive symptoms (CES-D<16). Not being married, self-rated poor health, greater frequency of injection drug use, history of overdose, no alcohol use, and daily cigarette smoking were positively associated with severe depressive symptoms in unadjusted models and remained predictive in a multivariable model. The strongest predictors of depressive symptoms were self-reported poor health (POR = 2.94, 95% CI: 1.82, 4.76), no current alcohol use (POR = 2.35, 95% CI: 1.47, 3.77), and not currently married or cohabitating (POR = 2.21, 95% CI = 1.40, 3.47). CONCLUSION: Severe depressive symptoms were common among HIV-positive PWID in Thai Nguyen and were strongly associated with demographic, clinical, and psychosocial factors. Interventions that promote social support from family and reduce drug dependence may particularly benefit PWID experiencing severe depressive symptoms. Greater recognition and treatment of depressive symptoms has the potential to enhance quality of life and improve HIV clinical outcomes for PWID.

Increased Survival Among HIV-Infected PWID Receiving a Multi-Level HIV Risk and Stigma Reduction Intervention: Results From a Randomized Controlled Trial.

OBJECTIVE: In Vietnam, where 58% of prevalent HIV cases are attributed to people who inject drugs, we evaluated whether a multi-level intervention could improve care outcomes and increase survival. METHODS: We enrolled 455 HIV-infected males who inject drugs from 32 communes in Thai Nguyen Province. Communes were randomized to a community stigma reduction intervention or standard of care and then within each commune, to an individual enhanced counseling intervention or standard of care, resulting into 4 arms: Arm 1 (standard of care); Arm 2 (community intervention alone); Arm 3 (individual intervention alone); and Arm 4 (community + individual interventions). Follow-up was conducted at 6, 12, 18, and 24 months to assess survival. RESULTS: Overall mortality was 23% (n = 103/455) more than 2 years. There were no losses to follow-up for the mortality endpoint. Survival at 24 months was different across arms: Arm 4 (87%) vs Arm 1 (82%) vs Arm 2 (68%) vs Arm 3 (73%); log-rank test for comparison among arms: P = 0.001. Among those with CD4 cell count <200 cells/mm and not on antiretroviral therapy at baseline (n = 162), survival at 24 months was higher in Arm 4 (84%) compared with other arms (Arm 1: 61%; Arm 2: 50%; Arm 3: 53%; P-value = 0.002). Overall, Arm 4 (community + individual interventions) had increased uptake of antiretroviral therapy compared with Arms 1, 2, and 3. CONCLUSIONS: This multi-level behavioral intervention seemed to increase survival of HIV-infected participants more than a 2-year period. Relative to the standard of care, the greatest intervention effect was among those with lower CD4 cell counts.

Co-calibration of two self-reported measures of adherence to antiretroviral therapy.

Adherence to antiretroviral therapy (ART) is an important determinant of clinical success assessed in many HIV studies. Harmonizing adherence data from studies that use different measures is difficult without a co-calibration equation to convert between validated instruments. Our purpose was to co-calibrate two commonly used adherence measures: the AIDS Clinical Trials Group (ACTG) questionnaire and the Visual Analog Scale (VAS). We used robust linear regression to develop a co-calibration equation in a clinical care cohort. The outcome was the 30-day VAS percentage of ART taken and the predictors were ACTG questions. We evaluated the equation's goodness of fit in five STTR (Seek, Test, Treat, Retain) consortium studies where individuals completed both measures: 2 criminal justice; 2 international; and 1 other high-risk vulnerable population. We developed a three-phase decision rule to convert ACTG to VAS in 1045 participants. First, when the last missed dose on the ACTG was reported as >30 days ago, the VAS was set to 100% (N = 582). Second, if "doses missed" was zero for all items, VAS was 100% (N = 104). Third, among remaining participants (N = 359), VAS was estimated as 96.8% minus 2.9% times the number of missed doses ("doses per day" was non-significant). Correlation between predicted and reported VAS was r = 0.80 in the criminal justice group (N = 446), r = 0.46 in the international group (N = 311), r = 0.32 in the other vulnerable population (N = 63), and r = 0.66 overall. When outliers due to inversion of the VAS scale were excluded (n = 25), these correlations were 0.88, 0.78, 0.80, and 0.86, respectively. We concluded that a simple decision rule and equation allowed us to co-calibrate between two widely used adherence measures thus combining data from studies with different instruments. This study highlighted issues with VAS inversions and its limitations as a single item. Combining studies using different instrument facilitates larger pooled datasets to address key research questions.

The Effect of a Multi-Level Intervention on the Initiation of Antiretroviral Therapy (ART) among HIV-Infected Men Who Inject Drugs and Were Diagnosed Late in Thai Nguyen, Vietnam.

BACKGROUND: In Vietnam, an estimated 256,000 people are living with HIV, and 58% of HIV-infections reported are among people who inject drugs (PWID). While antiretroviral therapy (ART) is widely available in Vietnam, marginalized hard-to-reach male PWID, demonstrate significantly reduced and delayed access to ART. METHODS: We investigated the effect of a randomized four-arm multi-level intervention trial on ART initiation among male PWID. Our analysis was conducted among a subset of trial participants (n = 136), who were newly diagnosed as HIV-infected, treatment naïve, and eligible for ART (baseline late diagnosis). The trial arms included: 1, standard of care (HIV testing and counseling); 2, structural-level intervention (door-to-door communications and community video screenings); 3, individual-level intervention (counseling plus group support); and 4, individual-level plus structural-level intervention. In a time-to-event analysis, we used a non-parametric approach for competing risks to estimate cumulative incidence function (CIF) for ART initiation (event of interest) by arm and the difference in CIF for each trial arm as compared to Arm 1. Follow-up was conducted at 6, 12, 18 and 24 months. Data collection occurred from 2009 to 2013. FINDINGS: By 24-months, 61.0% initiated ART, and 30.9% had died prior to ART initiation. In the first 6 months, participants in arm 4 (individual plus community intervention) had a 28% (95% confidence interval (CI): 6-50%) increased probability of initiating ART. Despite increasing coverage of ART in all arms throughout follow-up, participants in arm 4 retained a 31% (95% CI: 5-56%) increased probability of initiating ART. The individual and community components of the intervention were only effective when delivered together. CONCLUSIONS: Marginalized, hard-to-reach men, who do not routinely engage in HIV services, and therefore come into care late, may benefit significantly from both individual counseling and group support, in combination with community-focused stigma reduction, when being referred and attempting to initiate urgently needed ART.

Roles and Functions of Social Networks Among Men Who Use Drugs in ART Initiation in Vietnam.

Support from social network members may help to facilitate access to HIV medical care, especially in low resourced communities. As part of a randomized clinical trial of a community-level stigma and risk reduction intervention in Thai Nguyen, Vietnam for people living with HIV who inject drugs (PWID), 341 participants were administered a baseline social network inventory. Network predictors of antiretroviral therapy (ART) initiation at the 6-month follow-up were assessed. The social networks of PWID were sparse. Few participants who reported injectors in their networks also reported family members, whereas those who did not have injectors were more likely to report family members and network members providing emotional support and medical advice. In multivariate models, having at least one network member who provided medical advice predicted ART initiation at 6 months (OR 2.74, CI 1.20-6.28). These results suggest the importance of functional social support and network support mobilization for ART initiation among PWID.

Variations in the Role of Social Support on Disclosure Among Newly Diagnosed HIV-Infected People Who Inject Drugs in Vietnam.

Stigma and perceived social support can influence the decision to disclose HIV positive status, especially for people who inject drugs (PWID). In this analysis, the association between social support and HIV disclosure among 336 newly diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after diagnosis, 34.8 % of participants had not disclosed to anyone. Disclosure to anyone and to a family member specifically, was associated with baseline social support in the form of positive interactions and a history of incarceration. Disclosing to a family member was less likely among those who had unprotected sex in the previous 3 months. Disclosure to an injecting partner was more likely among those with a history of being in a drug treatment program, knowing someone on ART and believing that ART is safe. These data suggest that social support may facilitate disclosure among family members, including spouses, while disclosure to injecting partners is greater when PWID know that ART is a safe and viable option.

Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.

In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named "Bone Marrow (BM) Soup", was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and "deactivated BM Soup" were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the 'deactivated BM Soup' was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies.