MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations.

The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). We previously developed MitoCarta, a catalogue of over 1000 genes encoding the mammalian mitochondrial proteome. This catalogue was compiled using a Bayesian integration of multiple sequence features and experimental datasets, notably protein mass spectrometry of mitochondria isolated from fourteen murine tissues. Here, we introduce MitoCarta3.0. Beginning with the MitoCarta2.0 inventory, we performed manual review to remove 100 genes and introduce 78 additional genes, arriving at an updated inventory of 1136 human genes. We now include manually curated annotations of sub-mitochondrial localization (matrix, inner membrane, intermembrane space, outer membrane) as well as assignment to 149 hierarchical 'MitoPathways' spanning seven broad functional categories relevant to mitochondria. MitoCarta3.0, including sub-mitochondrial localization and MitoPathway annotations, is freely available at http://www.broadinstitute.org/mitocarta and should serve as a continued community resource for mitochondrial biology and medicine.

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

BACKGROUND: Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. METHODS/DESIGN: The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. DISCUSSION: Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. TRIAL REGISTRATION: ClinicalTrials.gov NCT02475538 .

Adolescent Emotional Pathology and Lifetime History of Alcohol or Drug Use With and Without Comorbid Tobacco Use.

OBJECTIVE: Use of drugs and alcohol, including tobacco, is linked to adolescent emotional psychopathology. Given that tobacco use is becoming less common over recent years, its co-use with drugs/alcohol may mark a more severe profile of emotional symptomatology. However, it is unclear whether teens with a lifetime history of using drug/alcohol and tobacco exhibit additional elevations in emotional psychopathology and/or multiple forms of emotional psychopathology compared to teens with lifetime drug/alcohol use without comorbid tobacco use. This cross-sectional study compared emotional disorder symptoms and emotional vulnerability traits among adolescents with varying histories of substance use. METHODS: Ninth-grade students enrolled at two schools in Los Angeles, California, were recruited; 575 met eligibility criteria and provided both student assent and parental consent. Students completed self-report measures of emotional pathology, transdiagnostic, and lifetime substance use. Participants were classified into three groupings: (a) no history of substance use (n = 294); (b) lifetime history of drug/alcohol use without tobacco use (n = 166); and (c) lifetime history of drug/alcohol use with concomitant tobacco use (n = 115). RESULTS: Chi-square results showed that teens with lifetime alcohol/drug use with (vs. without) comorbid tobacco use were more likely to have used 10 of 16 substances assessed in the study. Post-ANOVA pairwise tests revealed that, compared to students with no history of substance use, those with any history of use (alcohol/drugs with and without tobacco use) had higher major depression symptoms and negative affect. Those with lifetime alcohol/drug use with comorbid tobacco use had higher generalized anxiety symptoms and distress, and those with lifetime alcohol/drug use without comorbid tobacco use had higher panic disorder symptoms and anhedonia. There were no significant differences between adolescents with lifetime drug/alcohol use with comorbid tobacco use versus those without tobacco use. CONCLUSIONS: Adolescents with (vs. without) a lifetime history of drug/alcohol use endorse greater emotional symptomatology and trait vulnerabilities, regardless of comorbid lifetime tobacco use. Thus, the extent to which tobacco serves as a gateway to, correlate of, or consequence of other substance use may have little bearing on adolescent emotional health. This study's findings further suggest that emotional vulnerability (in addition to manifest psychopathology) should be considered in adolescent substance use and mental illness prevention.

Envisioning a social-health information exchange as a platform to support a patient-centered medical neighborhood: a feasibility study.

BACKGROUND: Social determinants directly contribute to poorer health, and coordination between healthcare and community-based resources is pivotal to addressing these needs. However, our healthcare system remains poorly equipped to address social determinants of health. The potential of health information technology to bridge this gap across the delivery of healthcare and social services remains unrealized. OBJECTIVE, DESIGN, AND PARTICIPANTS: We conducted in-depth, in-person interviews with 50 healthcare and social service providers to determine the feasibility of a social-health information exchange (S-HIE) in an urban safety-net setting in Dallas County, Texas. After completion of interviews, we conducted a town hall meeting to identify desired functionalities for a S-HIE. APPROACH: We conducted thematic analysis of interview responses using the constant comparative method to explore perceptions about current communication and coordination across sectors, and barriers and enablers to S-HIE implementation. We sought participant confirmation of findings and conducted a forced-rank vote during the town hall to prioritize potential S-HIE functionalities. KEY RESULTS: We found that healthcare and social service providers perceived a need for improved information sharing, communication, and care coordination across sectors and were enthusiastic about the potential of a S-HIE, but shared many technical, legal, and ethical concerns around cross-sector information sharing. Desired technical S-HIE functionalities encompassed fairly simple transactional operations such as the ability to view basic demographic information, visit and referral data, and medical history from both healthcare and social service settings. CONCLUSIONS: A S-HIE is an innovative and feasible approach to enabling better linkages between healthcare and social service providers. However, to develop S-HIEs in communities across the country, policy interventions are needed to standardize regulatory requirements, to foster increased IT capability and uptake among social service agencies, and to align healthcare and social service priorities to enable dissemination and broader adoption of this and similar IT initiatives.

Pelvic ultrasonography and length of stay in the ED: an observational study.

OBJECTIVES: We compared emergency physician-performed pelvic ultrasonography (EPPU) with radiology department-performed pelvic ultrasonography (RPPU) in emergency department (ED) female patients requiring pelvic ultrasonography and their outcomes in relation to ED length of stay, ED readmission, and alternative diagnosis, within a 14-day follow-up period. METHODS: This was a prospective, observational study of female patients of reproductive age who required either an EPPU or RPPU for their ED evaluation. We hypothesized that patients receiving EPPU would have a length of stay reduction greater than or equal to 60 minutes, as compared with RPPU. Statistical analyses included an independent-samples t test and multivariate regression modeling to control for factors associated with ED LOS. RESULTS: Eighteen resident physicians performed EPPU, with 15 attending physicians supervising. Forty-eight patients received only EPPU, and 84 patients received only RPPU. In univariate analysis, those who received EPPU had an ED LOS 162 minutes less than those who received RPPU (95% confidence interval, 106-209 minutes). In multivariate analysis controlling for gynecologist consultation, disposition, and pregnancy status, patients who received EPPU had an ED LOS reduction of 108 minutes when compared with RPPU (95% confidence interval, 38-166 minutes). Five patients (10%) who had received EPPU and were discharged from the ED returned to the ED within 2 weeks, but none had alternative diagnoses. CONCLUSIONS: Patients with EPPU had statistically and clinically significant reductions in ED LOS, even when controlling for disposition, gynecologist consultation in the ED, and pregnancy status. No patients in the study had an alternative diagnosis within 2 weeks of EPPU.

Positron emission tomography combined with serum biomarkers detects fibrotic MASH.

Metabolic dysfunction-associated steatohepatitis (MASH) is a rising global disease signaling the urgent need for non-invasive tests (NITs). Recent work demonstrated that dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging can identify MASH by measuring liver glucose transport rate, K1, and liver CT attenuation. By combining dynamic PET/CT with the serum-based fibrosis-4 (FIB-4) test, we were able to better distinguish clinical MASH from fibrotic subtypes, enabling determination of the core tenets of MASH: steatosis, inflammation, and fibrosis. Future studies using FDG-PET technology can further enable concomitant prediction of MASH severity and extrahepatic comorbidities such as cardiovascular disease.

A pilot study examining the viability of a Prehospital Assessment with UltraSound for Emergencies (PAUSE) protocol.

BACKGROUND: Prehospital ultrasound has been shown to aid in the diagnosis of multiple conditions that do not generally change prehospital management. On the other hand, the diagnoses of cardiac tamponade, tension pneumothorax, or cardiac standstill may directly impact patient resuscitation in the field. STUDY OBJECTIVE: To determine if prehospital care providers can learn to acquire and recognize ultrasound images for several life-threatening conditions using the Prehospital Assessment with UltraSound for Emergencies (PAUSE) protocol. METHODS: This is a prospective, educational intervention pilot study at an urban fire department with integrated emergency medical services (EMS). We enrolled 20 emergency medical technicians--paramedic with no prior ultrasonography training. Subjects underwent a 2-h training session on basic ultrasonography of the lungs and heart to evaluate for pneumothorax, pericardial effusion, and cardiac activity. Subjects were tested on image interpretation as well as image acquisition skills. Two bedside ultrasound-trained emergency physicians scored images for adequacy. Image interpretation testing was performed using pre-obtained ultrasound clips containing normal and abnormal images. RESULTS: All subjects appropriately identified the pleural line, and 19 of 20 paramedics achieved a Cardiac Ultrasound Structural Assessment Scale score of ≥4. For the image interpretation phase, the mean PAUSE protocol video test score was 9.1 out of a possible 10 (95% confidence interval 8.6-9.6). CONCLUSION: Paramedics were able to perform the PAUSE protocol and recognize the presence of pneumothorax, pericardial effusion, and cardiac standstill. The PAUSE protocol may potentially be useful in rapidly detecting specific life-threatening pathology in the prehospital environment, and warrants further study in existing EMS systems.

The mitochondrial calcium uniporter transports Ca 2+ via a ligand-relay mechanism.

The mitochondrial calcium uniporter (mtCU) is a multicomponent Ca 2+ -specific channel that imparts mitochondria with the capacity to sense the cytosolic calcium signals. The metazoan mtCU comprises the pore-forming subunit MCU and the essential regulator EMRE, arranged in a tetrameric channel complex, and the Ca 2+ sensing peripheral proteins MICU1-3. The mechanism of mitochondrial Ca 2+ uptake by mtCU and its regulation is poorly understood. Our analysis of MCU structure and sequence conservation, combined with molecular dynamics simulations, mutagenesis, and functional studies, led us to conclude that the Ca 2+ conductance of MCU is driven by a ligand-relay mechanism, which depends on stochastic structural fluctuations in the conserved DxxE sequence. In the tetrameric structure of MCU, the four glutamate side chains of DxxE (the E-ring) chelate Ca 2+ directly in a high-affinity complex (site 1), which blocks the channel. The four glutamates can also switch to a hydrogen bond-mediated interaction with an incoming hydrated Ca 2+ transiently sequestered within the D-ring of DxxE (site 2), thus releasing the Ca 2+ bound at site 1. This process depends critically on the structural flexibility of DxxE imparted by the adjacent invariant Pro residue. Our results suggest that the activity of the uniporter can be regulated through the modulation of local structural dynamics. A preliminary account of this work was presented at the 67 th Annual Meeting of the Biophysical Society in San Diego, CA, February 18-22, 2023.

Stereotactic ablative radiotherapy for medically inoperable early stage lung cancer: early outcomes.

OBJECTIVE. To evaluate the clinical outcome and safety of stereotactic ablative radiotherapy for medically inoperable stage I non-small-cell lung carcinoma. DESIGN. Retrospective case series. SETTING. Pamela Youde Nethersole Eastern Hospital, Hong Kong. PATIENTS. All patients with medically inoperable stage I non-small-cell lung carcinoma receiving stereotactic ablative radiotherapy since its establishment in 2008. MAIN OUTCOME MEASURES. Disease control rate, overall survival, and treatment toxicities. RESULTS. Sixteen stage I non-small-cell lung carcinoma patients underwent the procedure from June 2008 to November 2011. The median patient age was 82 years and the majority (81%) had moderate-to-severe co-morbidity based on the Adult Comorbidity Evaluation 27 index. With a median follow-up of 22 months, the 2-year primary tumour control rate, disease-free survival and overall survival rates were 91%, 71% and 87%, respectively. No grade 3 (National Cancer Institute Common Terminology Criteria for Adverse Events) or higher treatment-related complications were reported. CONCLUSION. Stereotactic ablative radiotherapy can achieve a high degree of local control safely in medically inoperable patients with early lung cancer.

Evaluation of drug load and polymer by using a 96-well plate vacuum dry system for amorphous solid dispersion drug delivery.

It is well recognized that poor dissolution rate and solubility of drug candidates are key limiting factors for oral bioavailability. While numerous technologies have been developed to enhance solubility of the drug candidates, poor water solubility continuously remains a challenge for drug delivery. Among those technologies, amorphous solid dispersions (SD) have been successfully employed to enhance both dissolution rate and solubility of poorly water-soluble drugs. This research reports a high-throughput screening technology developed by utilizing a 96-well plate system to identify optimal drug load and polymer using a solvent casting approach. A minimal amount of drug was required to evaluate optimal drug load in three different polymers with respect to solubility improvement and solid-state stability of the amorphous drug-polymer system. Validation of this method was demonstrated with three marketed drugs as well as with one internal compound. Scale up of the internal compound SD by spray drying further confirmed the validity of this method, and its quality was comparable to a larger scale process. Here, we demonstrate that our system is highly efficient, cost-effective, and robust to evaluate the feasibility of spray drying technology to produce amorphous solid dispersions.

Effect of soluble amyloid precursor protein-alpha on adult hippocampal neurogenesis in a mouse model of Alzheimer's disease.

Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer's disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse model of Alzheimer's disease. An adeno-associated virus-9 (AAV9) encoding murine sAPPα was injected into the hippocampus of 8-month-old wild-type and APP/PS1 mice, and later two different thymidine analogues (XdU) were systemically injected to label adult-born cells at different time points after viral transduction. The proliferation of adult-born cells, cell survival after eight weeks, and cell differentiation into either neurons or astrocytes was studied. Proliferation was impaired in APP/PS1 mice but was restored to wild-type levels by viral expression of sAPPα. In contrast, sAPPα overexpression failed to rescue the survival of XdU+-labelled cells that was impaired in APP/PS1 mice, although it did cause a significant increase in the area density of astrocytes in the granule cell layer across both genotypes. Finally, viral expression of sAPPα reduced amyloid-beta plaque load in APP/PS1 mice in the dentate gyrus and somatosensory cortex. These data add further evidence that increased levels of sAPPα could be therapeutic for the cognitive decline in AD, in part through restoration of the proliferation of neural progenitor cells in adults.

Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kα.

Small molecule inhibitors that target the phosphatidylinositol 3-kinase (PI3K) signaling pathway have received significant interest for the treatment of cancers. The class I isoform PI3Kα is most commonly associated with solid tumors via gene amplification or activating mutations. However, inhibitors demonstrating both PI3K isoform and mutant specificity have remained elusive. Herein, we describe the optimization and characterization of a series of benzoxazepin-oxazolidinone ATP-competitive inhibitors of PI3Kα which also induce the selective degradation of the mutant p110α protein, the catalytic subunit of PI3Kα. Structure-based design informed isoform-specific interactions within the binding site, leading to potent inhibitors with greater than 300-fold selectivity over the other Class I PI3K isoforms. Further optimization of pharmacokinetic properties led to excellent in vivo exposure and efficacy and the identification of clinical candidate GDC-0077 (inavolisib, 32), which is now under evaluation in a Phase III clinical trial as a treatment for patients with PIK3CA-mutant breast cancer.

A framework for characterizing eHealth literacy demands and barriers.

BACKGROUND: Consumer eHealth interventions are of a growing importance in the individual management of health and health behaviors. However, a range of access, resources, and skills barriers prevent health care consumers from fully engaging in and benefiting from the spectrum of eHealth interventions. Consumers may engage in a range of eHealth tasks, such as participating in health discussion forums and entering information into a personal health record. eHealth literacy names a set of skills and knowledge that are essential for productive interactions with technology-based health tools, such as proficiency in information retrieval strategies, and communicating health concepts effectively. OBJECTIVE: We propose a theoretical and methodological framework for characterizing complexity of eHealth tasks, which can be used to diagnose and describe literacy barriers and inform the development of solution strategies. METHODS: We adapted and integrated two existing theoretical models relevant to the analysis of eHealth literacy into a single framework to systematically categorize and describe task demands and user performance on tasks needed by health care consumers in the information age. The method derived from the framework is applied to (1) code task demands using a cognitive task analysis, and (2) code user performance on tasks. The framework and method are applied to the analysis of a Web-based consumer eHealth task with information-seeking and decision-making demands. We present the results from the in-depth analysis of the task performance of a single user as well as of 20 users on the same task to illustrate both the detailed analysis and the aggregate measures obtained and potential analyses that can be performed using this method. RESULTS: The analysis shows that the framework can be used to classify task demands as well as the barriers encountered in user performance of the tasks. Our approach can be used to (1) characterize the challenges confronted by participants in performing the tasks, (2) determine the extent to which application of the framework to the cognitive task analysis can predict and explain the problems encountered by participants, and (3) inform revisions to the framework to increase accuracy of predictions. CONCLUSIONS: The results of this illustrative application suggest that the framework is useful for characterizing task complexity and for diagnosing and explaining barriers encountered in task completion. The framework and analytic approach can be a potentially powerful generative research platform to inform development of rigorous eHealth examination and design instruments, such as to assess eHealth competence, to design and evaluate consumer eHealth tools, and to develop an eHealth curriculum.

A technology selection framework for supporting delivery of patient-oriented health interventions in developing countries.

Health information technologies (HIT) have great potential to advance health care globally. In particular, HIT can provide innovative approaches and methodologies to overcome the range of access and resource barriers specific to developing countries. However, there is a paucity of models and empirical evidence informing the technology selection process in these settings. We propose a framework for selecting patient-oriented technologies in developing countries. The selection guidance process is structured by a set of filters that impose particular constraints and serve to narrow the space of possible decisions. The framework consists of three levels of factors: (1) situational factors, (2) the technology and its relationship with health interventions and with target patients, and (3) empirical evidence. We demonstrate the utility of the framework in the context of mobile phones for behavioral health interventions to reduce risk factors for cardiovascular disease. This framework can be applied to health interventions across health domains to explore how and whether available technologies can support delivery of the associated types of interventions and with the target populations.

Towards an improved understanding of drug excipient interactions to enable rapid optimization of nanosuspension formulations.

Suspensions of drug nanoparticles known as nanosuspensions have emerged as a successful enabling formulation approach for poorly soluble drug candidates. These nanoparticles typically require stabilization with specific polymer or surfactant excipients to prevent aggregation from occurring. This study demonstrates the necessity of formulating drug nanosuspensions with amphiphilic excipients possessing long hydrophobic alkyl or polymer block chains to produce stable nanoparticles. 28 different excipients and excipient combinations at various loadings were screened across the 3 drug compounds and their effectiveness, as characterized by the lowest excipient loading needed to stabilize a monodisperse drug suspension, is quantified as a function of various excipient parameters such as molecular weight, HLB value, CMC, H-bond donors and acceptors, and the length of the hydrophobic alkyl chains and polymer blocks within their molecular structure. Traditional characterization parameters (molecular weight, HLB value, and CMC) fail to predict excipient effectiveness. The conformational flexibility and length of the hydrophobic regions of amphiphilic excipients appears to be critical for effectiveness. This hypothesis was supported by molecular modeling studies to better understand the interactions between the excipients with the drug nanoparticle surface.

Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

BACKGROUND: Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic. METHODS: Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the effect of ART switch on HIV RNA over time. RESULTS: Eighty-three PWH had DNA GT performed, 66 (80%) switched ART, and 59 had postswitch follow-up. Data were analyzed pre-/postswitch for these 59 PWH (median age, 54 years; 71% LWH ≥10 years; 46% ≥2 previous regimens; 36% recent low-level viremia; 34% unknown medication history). On DNA GT, 58% had ≥1-class ART resistance, 34% ≥2-class, and 10% 3-class. Median follow-up (range) was 337 (34-647) days. There was no change in probability of HIV RNA ≥50 copies/mL over time (P > .05). At baseline, 76% had HIV RNA <50 vs 88% at last postswitch follow-up (P = .092). Protease inhibitor use decreased from 58% to 24% (P < .001). Average daily pills and dosing frequency decreased from 3.48 to 2.05 (P < .001) and 1.39 to 1.09 (P < .001), respectively; ART cost did not change. CONCLUSIONS: DNA GT facilitated changes in ART in a treatment-experienced population without increases in HIV RNA. Decreased pill burden occurred without increased ART cost. Further studies to identify optimal use of DNA GT are needed.

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments.

Assessing the need for an online decision-support tool to promote evidence-based practices of psychosocial counseling in HIV care.

Psychosocial counselors have a vital and challenging role in supporting persons living with HIV/AIDS (PLWH/A) to better manage their disease. However, gaps in training, education, and skills limit the effectiveness of counselors' efforts. We propose that the use of a decision-support tool for counselors at the point of care can support them in their work as well as help alleviate many training and practice gaps. Decision-support tools aimed at reducing knowledge and practice gaps are used extensively to assist clinical providers at the point of care; however, there is a need for decision-support tools designed specifically for HIV/AIDS counselors. To identify requirements for such a tool, we conducted a needs assessment through interviews of 19 HIV/AIDS clinic counselors who provide 20 or more hours per week of psychosocial support to PLWH/A. The assessment explored their education and training backgrounds, the extent to which evidence-based practices are implemented, and how a decision-support tool can support counselor work practices. Qualitative analysis was organized around seven main categories: counselor characteristics, patient characteristics, barriers, definitions of key concepts, use of guidelines, client assessments, and resources. The resulting coding schemes revealed knowledge and practice gaps among the interviewees, as well as barriers and challenges of counseling. Education and training background of the counseling staff varied widely. When asked to define five key concepts related to HIV counseling, 26-47% of respondents were unable to articulate an adequate definition. Less than half of the interviewees recalled sources of guidelines used in their work and specific models of care introduced during trainings. Interviews identified environmental barriers, language and literacy, patient education, and patient communication as the most prominent challenges to counseling work. The results from this study inform the need for and development of a decision-support tool to support the training and practices of HIV/AIDS counselors.

Mobile phones as mediators of health behavior change in cardiovascular disease in developing countries.

The global burden of cardiovascular diseases (CVD) is becoming a growing problem in developing countries. Successful self-management of CVD is dependent on a multitude of factors, including social support, communication with health care providers, careful monitoring, and other determinants. The growing market penetration and the communication properties of mobile phones create opportunities for innovation in promoting CVD self-management through support of lifestyle and behavior modification. Mobile phones support various modes of communication and interaction, have fewer adoption barriers, and are more prevalent than other available technologies in developing countries. However, mobile phone interventions are not without many challenges such as mobile infrastructure, electric infrastructure, access to mobile devices, and appropriate user interfaces for interaction. In this paper, we discuss current evidence as well as research opportunities to explore the role of mobile phones in supporting behavior modification in developing countries.

Vitamin E Acetate as a Plausible Cause of Acute Vaping-related Illness.

The United States Federal Centers for Disease Control and Prevention (CDC) has been working with state investigators on reported cases of lung illnesses linked to e-cigarette or vaping products. Symptoms of difficulty breathing, shortness of breath, chest pains, gastrointestinal sickness leading to serious lung damage and death has been linked to the risk behavior of using vaping products bought on the streets in healthy young people. CDC has detected vitamin E acetate as a chemical of concern among people with the lung injury. Vitamin E acetate is a condensing agent in vaping products, and all injured lung fluid samples appear to harbor this agent. The mysterious outbreak is identified in individuals vaping within the 90 days, ranging over a few days to developing over several weeks. There is growing evidence that vaping is hazardous to your health including immediate health dangers such as death from respiratory causes, long term health effects, cardiovascular events, depression which increases the risk of suicidal thoughts and suicide. This review article summarizes the growing knowledge of acute respiratory complications associated with vaping.