Telemedicine Security: Challenges and Solutions

The proliferation of telemedicine spurred by the COVID-19 pandemic has come with a variety of human factors challenges. Such challenges include mitigating potential risks associated with the quick transition to virtual care. We identify challenges and solutions related to telemedicine security, and analyze our results using Schlarman’s People, Policy, Technology framework (2001). Our systematic literature review synthe-sizes gray literature (white papers, news articles, and blog posts) in addition to formal (published) litera-ture. This methodology closes the gap between academic research and professional practice and aids in providing timely, practical insights related to cybersecurity and safety in virtual care environments. As the transition from traditional care continues to develop, we seek to better understand emerging vulnerabilities, identify crucial cyber hygiene practices, and provide insights on how to improve the safety of paitent data in virtiual care. Telemedicine is here to stay, and lessons learned from the pandemic are likely to remain useful

Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating

While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding). In contrast, inhibition of the nucleus accumbens (NAc), through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive

The associations of smoking dependence motives with depression among daily smokers

Aims To investigate how strongly smoking dependence and smoking dependence motives are associated with depressive symptoms among daily smokers and if these associations are independent of measured confounders and shared familial factors. Design Cross-sectional individual-based and within-pair analyses. Setting Fourth wave of the population-based Finnish Twin Cohort conducted in 2011. Participants 918 daily smokers born 1945-1957 (48% men), mean age 59.5 years including 38 twin pairs discordant for depression. Measurements Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale with a cut off value >= 20 for depression. Smoking dependence was assessed using the Fagerstrom Test for Cigarette Dependence (FTCD) and smoking dependence motives with three subscales from the multi-dimensional Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM): primary dependence motives (PDM), affective enhancement (AE), and Taste. Logistic regressions, using standardized scores of independent variables and adjusted for multiple confounders with correction for sampling as twin pairs, were used in the individual-based analyses. Conditional logistic regression was used to control for shared familial factors in discordant twin pairs. Findings Prevalence of depression was 18% (n = 163: 61 [14%] in men, n = 102 [22%] in women). Higher smoking dependence measured by the FTCD (OR 1.45; 95% CI 1.20, 1.75), and dependence motives measured by the PDM (1.56; 1.30, 1.87) and the AE (1.54; 1.28, 1.85) were associated with higher odds of depression. The associations remained after adjusting for individual confounders, except for neuroticism, which attenuated all associations. FTCD, PDM, and AE showed associations with depression within depression-discordant monozygotic pairs, suggesting an association independent of familial factors. Conclusions Depression appears to be associated with smoking dependence and smoking dependence motives related to heavy, automatic use and use to regulate affective states. The associations appear to be confounded or mediated by neuroticism but are independent of shared familial influences.Peer reviewe

Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis

Effective tuberculosis treatment requires at least 6 months of combination therapy. Alterations in the physiological state of the bacterium during infection are thought to reduce drug efficacy and prolong the necessary treatment period, but the nature of these adaptations remain incompletely defined. To identify specific bacterial functions that limit drug effects during infection, we employed a comprehensive genetic screening approach to identify mutants with altered susceptibility to the first-line antibiotics in the mouse model. We identified many mutations that increase the rate of bacterial clearance, suggesting new strategies for accelerating therapy. In addition, the drug-specific effects of these mutations suggested that different antibiotics are limited by distinct factors. Rifampin efficacy is inferred to be limited by cellular permeability, whereas isoniazid is preferentially affected by replication rate. Many mutations that altered bacterial clearance in the mouse model did not have an obvious effect on drug susceptibility using in vitro assays, indicating that these chemical-genetic interactions tend to be specific to the in vivo environment. This observation suggested that a wide variety of natural genetic variants could influence drug efficacy in vivo without altering behavior in standard drug-susceptibility tests. Indeed, mutations in a number of the genes identified in our study are enriched in drug-resistant clinical isolates, identifying genetic variants that may influence treatment outcome. Together, these observations suggest new avenues for improving therapy, as well as the mechanisms of genetic adaptations that limit it. IMPORTANCE Understanding how Mycobacterium tuberculosis survives during antibiotic treatment is necessary to rationally devise more effective tuberculosis (TB) chemotherapy regimens. Using genome-wide mutant fitness profiling and the mouse model of TB, we identified genes that alter antibiotic efficacy specifically in the infection environment and associated several of these genes with natural genetic variants found in drug-resistant clinical isolates. These data suggest strategies for synergistic therapies that accelerate bacterial clearance, and they identify mechanisms of adaptation to drug exposure that could influence treatment outcome

A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase

Inositol pentakisphosphate 2-kinase catalyzes the phosphorylation of the axial 2-OH of myo-inositol 1,3,4,5,6-pentakisphosphate for de novo synthesis of myo-inositol hexakisphosphate. Disruption of inositol pentakisphosphate 2-kinase profoundly influences cellular processes; from nuclear mRNA export and phosphate homeostasis in yeast and plants, to establishment of left-right asymmetry in zebra fish. We elaborate an active site fluorescent probe that allows high throughput screening of Arabidopsis inositol pentakisphosphate 2-kinase. We show that the probe has a binding constant comparable to the Km values of inositol phosphate substrates of this enzyme, and can be used to prospect for novel substrates and inhibitors of inositol phosphate kinases. We identify several micromolar Ki inhibitors and validate this approach by solving the crystal structure of protein in complex with purpurogallin. We additionally solve structures of protein in complexes with epimeric higher inositol phosphates. This probe may find utility in characterization of a wide family of inositol phosphate kinases

A New Obesity Model Reveals the Hypophagic Properties of PACAP Involve the Regulation of Homeostatic Feeding in the Ventromedial Hypothalamic Nucleus and Hedonic Feeding in the Nucleus Accumbens

Binge eating in humans is a complex disorder that often involves discrete, compulsive feeding sessions of highly palatable foods even in the absence of a deprivation state or hunger. Binging can be effectively modeled in rodents by providing subjects with limited access to a palatable food source (Western Diet; WD) as an adjunct to ad lib access to normal chow (Standard Chow; SC). Although this design recapitulates several fundamental characteristics observed in binge eating disorder, the binge eating observed in this paradigm is likely a product of both hedonic and homeostatic drives with the need to balance energy stores still present. To isolate these feeding drives, we have developed a novel feeding regimen that modifies the classic limited access binge model to effectively delineate and separate homeostatic feeding from motivational feeding. This is achieved by entraining male Sprague-Dawley rats to a restricted feeding schedule (two hours per day) of SC followed by a short 15 minute limited access meal of either SC or WD (Restrict Fed-Limited Access; RFLA). The RFLA paradigm allows for the examination of pituitary adenylate-cyclase activating polypeptide (PACAP) on palatable food consumption in a fully satiated subject. PACAP has previously been shown to suppress feeding behavior when injected into the hypothalamus. In the current study, PACAP injected into the ventromedial hypothalamic nuclei (VMN) suppressed the two hour homeostatic SC meal, but not the subsequent 15 minute limited access meal of WD. By contrast, PACAP bilaterally administered into the nucleus accumbens (NAc) produced the opposite effect with PACAP suppressing the consumption of WD but not SC. Thus, PACAP mediated signaling in the VMN appears to be involved in homeostatic regulation of energy stores, whereas PACAP signaling in the NAc regulates feeding driven by palatability or hedonic qualities

No Change in Perceptual or Chronotropic Outcome When Altering Preferred Step Frequency for a Short Duration

IIntroduction: Millions of individuals incorporate jogging into their physical activity routines as a leisurely pursuit and as a way to achieve positive health outcomes. People appear to choose jogging speed and the associated step frequency on pure, natural preference. Understandably, kinesthetics are important, but another important underlying factor is metabolic cost. The purpose of this work was to investigate if preferred step frequency (at a preferred jogging pace) also minimizes perceived effort (Borg Rating of Perceived Exertion, 6-20; RPE) and chronotropic stress (heart rate; HR) during a ten-minute activity bout when compared with step frequencies altered by 5%. Methods: Recreationally-trained male subjects underwent two testing visits. The first visit was used to establish RPE and HR responses during a 10-minute jogging activity at preferred speed and step frequency. On a subsequent visit, between two and four days later, with preferred speed maintained, subjects were guided by metronome to strike at either 95% or 105% of their preferred step frequency. The 10-minute runs were randomized, crossed-over, and separated by 20 minutes. RPE and HR were analyzed by repeated measures ANOVA. Results: Fourteen subjects (age: 21.1 ± 0.95; body mass index: 23.2 ± 2.5) enrolled. Preferred jogging speed (speed. 6.4 ± 1.0 miles per hour; 10.2 ± 1.6 kilometers per hour) and step frequency (steps. 161.2 ± 10.3 steps/minute) were determined at the first visit, along with RPE (11.3 ± 1.7) and HR (166.4 ± 12.7). At the second visit, preferred speed was maintained while the frequency of foot-strike was altered. Neither differences in RPE (p = 0.252; 11.3 ± 1.7, 11.6 ± 1.9, 11.8 ± 1.5) nor HR (p = 0.547; 166.4 ± 12.7, 164.7 ± 14.9, 165.2 ± 15.3) were different when comparing the preferred, 95%, and 105% step frequency trials, respectively. Although anecdotal, some subjects verbalized displeasure with the change in pace and most all appeared to markedly alter the initial foot strike phase of the gait to meet the directed foot strike tempo. Discussion: Our data must be interpreted cautiously. While altering step frequency by 5% for a short duration does not appear to alter an individual’s RPE or HR appreciably, the result during longer duration activity may not be the same. In addition, the implications for biomechanical loading and metabolic cost were not presently investigated

Measuring psychological pain: psychometric analysis of the Orbach and Mikulincer Mental Pain Scale

Background: Suicide is a public health concern, with an estimated 1 million individuals dying each year worldwide. Individual psychological pain is believed to be a contributing motivating factor. Therefore, establishing a psychometrically sound tool to adequately measure psychological pain is important. The Orbach and Mikulincer Mental Pain Scale (OMMP) has been proposed; however, previous psychometric analysis on the OMMP has not yielded a consistent scale structure, and the internal consistency of the subscales has not met recommended values. Therefore, the primary purpose of this study was to assess the psychometric properties of the OMMP in a diverse sample. Methods: A confirmatory factor analysis (CFA) on the 9-factor, 44-item OMMP was conducted on the full sample (n = 1151). Because model fit indices were not met, an exploratory factor analysis (EFA) was conducted on a random subset of the data (n = 576) to identify a more parsimonious structure. The EFA structure was then tested in a covariance model in the remaining subset of participants (n = 575). Multigroup invariance testing was subsequently performed to examine psychometric properties of the refined scale. Results: The CFA of the original 9-factor, 44-item OMMP did not meet recommended model fit recommendations. The EFA analysis results revealed a 3-factor, 9-item scale (i.e., OMMP-9). The covariance model of the OMMP-9 indicated further refinement was necessary. Multigroup invariance testing conducted on the final 3-factor, 8-item scale (i.e., OMMP-8) across mental health diagnoses, sex, injury status, age, activity level, and athlete classification met all criteria for invariance. Conclusions: The 9-factor, 44-item OMMP does not meet recommended measurement criteria and should not be recommended for use in research and clinical practice in its current form. The refined OMMP-8 may be a more viable option to use; however, more research should be completed prior to adoption

Common Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy

Despite the administration of multiple drugs that are highly effective in vitro, tuberculosis (TB) treatment requires prolonged drug administration and is confounded by the emergence of drug-resistant strains. To understand the mechanisms that limit antibiotic efficacy, we performed a comprehensive genetic study to identify Mycobacterium tuberculosis genes that alter the rate of bacterial clearance in drug-treated mice. Several functionally distinct bacterial genes were found to alter bacterial clearance, and prominent among these was the glpK gene that encodes the glycerol-3-kinase enzyme that is necessary for glycerol catabolism. Growth on glycerol generally increased the sensitivity of M. tuberculosis to antibiotics in vitro, and glpK-deficient bacteria persisted during antibiotic treatment in vivo, particularly during exposure to pyrazinamide-containing regimens. Frameshift mutations in a hypervariable homopolymeric region of the glpK gene were found to be a specific marker of multidrug resistance in clinical M. tuberculosis isolates, and these loss-of-function alleles were also enriched in extensively drug-resistant clones. These data indicate that frequently observed variation in the glpK coding sequence produces a drug-tolerant phenotype that can reduce antibiotic efficacy and may contribute to the evolution of resistance. IMPORTANCE: TB control is limited in part by the length of antibiotic treatment needed to prevent recurrent disease. To probe mechanisms underlying survival under antibiotic pressure, we performed a genetic screen for M. tuberculosis mutants with altered susceptibility to treatment using the mouse model of TB. We identified multiple genes involved in a range of functions which alter sensitivity to antibiotics. In particular, we found glycerol catabolism mutants were less susceptible to treatment and that common variation in a homopolymeric region in the glpK gene was associated with drug resistance in clinical isolates. These studies indicate that reversible high-frequency variation in carbon metabolic pathways can produce phenotypically drug-tolerant clones and have a role in the development of resistance