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Introduction Mild parkinsonian signs (MPS) are associated with morbidity. Identification of MPS progression markers may be vital for preventive management, yet has not been pursued. This study aimed to ascertain clinical/neuroimaging features predictive of MPS progression. Methods 205 participants in the Health ABC Study were included. MPS was defined using published guidelines. MPS progression was evaluated by determining UPDRS-III change between baseline and follow-up ≥2 years later. Standard brain MRI and DTI were obtained at baseline. Correlation coefficients between demographics, vascular risk factors, imaging markers, and UPDRS-III change were adjusted for follow-up time. Linear regression was used to adjust for possible confounders in the relationship between imaging markers and MPS progression. Results 30% of participants had baseline MPS. Demographics and risk factors did not differ significantly between participants with MPS (MPS+) and without MPS (MPS-). Mean follow-up time was 3.8±0.8 years. Older age, male gender, diabetes were associated with faster rate of UPDRS-III change in MPS- but not MPS+ participants. Among MPS- participants, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity (MD), widespread in various cortico-subcortical bihemispheric regions, independent of age, gender, diabetes. No imaging features were associated with UPDRS-III change among MPS+ participants. Conclusions Lower gray matter integrity predicted MPS progression in those who did not have baseline MPS. Microstructural imaging may capture early changes related to MPS development, prior to macrostructural change. Any future management promoting gray matter preservation may inhibit MPS development.

Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI).A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects.There is a statistically significant increase of 0.369 kg/mThe potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

informCLL is the first United States-based registry of patients with chronic lymphocytic leukemia that initiated enrollment after approval of novel targeted agents. Prognostic/predictive testing rates and chronic lymphocytic leukemia treatment selection with availability of novel agents have not been previously investigated in clinical practice. Results from this interim analysis demonstrate that prognostic/predictive testing was infrequently used to guide treatment selection, potentially inhibiting beneficial outcomes for patients. Introduction: The therapeutic landscape for chronic lymphocytic leukemia (CLL) has significantly shifted with the approval of novel agents. Understanding current prognostic testing and treatment practices in this new era is critical. Beginning enrollment in 2015, informCLL is the first United States-based real-world, prospective, observational registry that initiated enrollment after approval of novel agents. Patients and Methods: Eligible patients were age ≥ 18 years, started CLL treatment within 30 days of enrollment, and provided consent. For this planned interim analysis, treatments were classified into 5 groups: ibrutinib, chemoimmunotherapy, chemotherapy, immunotherapy, and other novel agents. Results: Frequency of prognostic testing and treatment patterns are reported among 840 patients (459 previously untreated; 381 relapsed/refractory), enrolled largely (96%) from community practice settings. Testing for chromosomal abnormalities by fluorescence in situ hybridization, TP53 mutation, or IGHV mutation status occurred infrequently among all patients (31%, 11%, and 11%, respectively). Chemoimmunotherapy was the most common treatment in previously untreated patients (42%), whereas ibrutinib was the most common treatment among relapsed/ refractory patients (51%). Of patients who tested positive for del(17p) or TP53 mutation, 34% and 26% received chemoimmunotherapy, respectively. Among patients who did not have fluorescence in situ hybridization or TP53 mutation testing prior to enrollment, 33% and 32% received chemoimmunotherapy, respectively. Conclusion: Our findings indicate that prognostic testing rates were poor, and approximately one-third of high-risk patients (del[17p] and TP53) received chemoimmunotherapy, which is not aligned with current CLL treatment recommendations. This represents an opportunity to educate and alert health care professionals about the necessity of prognostic testing to guide optimal CLL treatment decisions.

Waves of highly infectious viruses sweeping through global honey bee populations have contributed to recent declines in honey bee health. Bees have been observed foraging on mushroom mycelium, suggesting that they may be deriving medicinal or nutritional value from fungi. Fungi are known to produce a wide array of chemicals with antimicrobial activity, including compounds active against bacteria, other fungi, or viruses. We tested extracts from the mycelium of multiple polypore fungal species known to have antiviral properties. Extracts from amadou (Fomes) and reishi (Ganoderma) fungi reduced the levels of honey bee deformed wing virus (DWV) and Lake Sinai virus (LSV) in a dose-dependent manner. In field trials, colonies fed Ganoderma resinaceum extract exhibited a 79-fold reduction in DWV and a 45,000-fold reduction in LSV compared to control colonies. These findings indicate honey bees may gain health benefits from fungi and their antimicrobial compounds.

At a time of resurgence in injection drug use and injection-attributable infections, needle stick injury (NSI) risk and its correlates among police remain understudied. In the context of occupational safety training, a convenience sample of 771 Baltimore city police officers responded to a self-administered survey. Domains included NSI experience, protective behaviors, and attitudes towards syringe exchange programs. Sixty officers (8%) reported lifetime NSI. Officers identifying as Latino or other race were almost three times more likely (aOR 2.58, 95% CI 1.12-5.96) to have experienced NSI compared to whites, after adjusting for potential confounders. Findings highlight disparate burdens of NSIs among officers of color, elevating risk of hepatitis, HIV, and trauma. Training, equipment, and other measures to improve occupational safety are critical to attracting and safeguarding police, especially minority officers.

Young women engaged in exotic dancing have a higher need for reproductive health services than women not in this profession, and many also use drugs or exchange sex for money or drugs. Few report receiving reproductive health services. We describe a public health, academic, and community partnership that provided reproductive health services on needle exchange mobile vans in the “red light district” in downtown Baltimore, Maryland. Women made 220 visits to the vans in the first 21 months of the program's operation, and 65% of these visits involved provision of contraception. Programmatic costs were feasible. Joint provision of needle exchange and reproductive health services targeting exotic dancers has the potential to reduce unintended pregnancies and link pregnant, substance-abusing women to reproductive care, and such programs should be implemented more widely.

Background Transvenous lead extraction carries a risk of significant complications. Although intraoperative transesophageal echocardiography (TEE) is widely used to monitor cardiac performance and structures, its utility during transvenous lead extraction has not been well described. Objective This study evaluates the utility of TEE during transvenous lead extraction. Methods The records of 108 consecutive patients who underwent transvenous lead extraction with TEE guidance were reviewed. Results Transvenous extraction of 202 leads was attempted; complete extraction was achieved for 174 leads (86%) and partial extraction for 13 leads with clinically acceptable outcomes in 187 leads (93%). Mean age of the patients was 63 ± 21 (14-99) years and 37% were female. The average number of leads per patient was 1.9 (1-6). Mean implant duration was 71 ± 57 (1-360) months. Indications for extraction were pocket infection (53 patients), bacteremia (33), atrial J-lead fracture or recall (13), lead malfunction (8), and venous thrombosis (1). TEE identified critical findings that prompted emergency surgical intervention or converted transvenous lead extraction to surgical explantation in 6 patients (two cases with cardiac laceration, 3 cases of cardiac tamponade, and one case with a large vegetation and a patent foramen ovale). TEE eliminated the need for the premature termination of the procedure in 11 patients by excluding significant structural cardiac damage. Overall, TEE provided clinically useful information during transvenous lead extraction in 17 cases (16%). Conclusions TEE during transvenous lead extraction provides valuable real-time information that improves efficacy and safety.

Objectives. We piloted a monitoring mechanism to document police encounters around programs targeting people who inject drugs (PWID), and assessed their demographic predictors at 2 Baltimore, Maryland, needle exchange program (NEP) sites. Methods. In a brief survey, 308 clients quantified, characterized, and sited recent police encounters. Multivariate linear regression determined encounter predictors, and we used geocoordinate maps to illustrate clusters. Results. Within the past 6 months, clients reported a median of 3 stops near NEP sites (interquartile range [IQR] = 0–7.5) and a median of 1 arrest in any location (IQR = 0–2). Three respondents reported police referral to the NEP. Being younger (P = .009), being male (P = .033), and making frequent NEP visits (P = .02) were associated with reported police stops. Among clients reporting arrest or citation for syringe possession, Whites were significantly less likely than non-Whites to report being en route to or from an NEP (P Conclusions. Systematic surveillance of structural determinants of health for PWID proved feasible when integrated into service activities. Improved monitoring is critical to informing interventions to align policing with public health, especially among groups subject to disproportionate levels of drug law enforcement.

An inherent limitation to the study of in vivo animal models of lymphedema is the potential inaccuracy or unreliability of existing methods for the quantification of edema volume as a surrogate functional measure of lymphatic transport capacity. Circumference-based techniques have been proposed and validated as a suitable alternative to volume displacement measurements in human clinical studies; accordingly, we have elaborated a new application of this approach that can be applied to small animal studies.Acute postsurgical lymphedema was created experimentally in the murine tail. Both normal and lymphedematous murine tails were examined. Tail volume was quantitated both by water displacement and by a digital photographic technique. In selected mice, after sacrificed on postsurgical day 7, a 6 cm segment was resected from the midportion of the tail and cauterized to create a closed space. Known incremental volumes of saline (20-100 microL) were injected for subsequent digital photographic volumetry.The coefficients of variation for volume assessment by water displacement and by digital imaging were 0.08+/-0.09 and 0.01+/-0.009, respectively. The two techniques were poorly correlated: while serial water displacement analysis yielded highly variable measurements within the same tail, concurrent digital imaging of the tail circumference was quite reproducible. Furthermore, after parenteral injection of known incremental volumes of saline, the correlation between the injectate volumes and the digitally measured increases in volume was high, both in the normal and the lymphedematous tail.In the murine tail, when compared to water displacement volumetry, digital photography yields highly reproducible data. We can conclude that the lack of correlation between the two methods, with the relatively flat slope of the linear regression relationship, reflects inherent inaccuracies of the water displacement method.

Dissipation of Functional Bundle Branch Block. Introduction: Linking-related anterograde functional bundle branch block during supraventricular tachycardia (SVT) is due to repetitive concealed retrograde conduction of impulses from the contralateral bundle branch and can be eliminated by a critically timed premature ventricular beat (PVB). We assessed the electrophysiologic characteristics of PVB-induced dissipation of functional bundle branch block during SVT. Methods and Results: During SVT with functional bundle branch block, PVB was delivered from the right ventricular apex, scanning the tachycardia cycle length (CL) with 10-msec decrements in the coupling interval in 14 patients (3 AV nodal reentrant tachycardia and 11 orthodromic AV reciprocating tachycardia). Dissipation was achieved in group 1: functional right bundle branch block (RBBB) in 4, functional left bundle branch block (LBBB) in 4, and both functional RBBB and LBBB in 1 with a dissipation zone occupying 4% to 13% (mean 8.5%) of the tachycardia CL. The outer limits were 22 ± 16 msec and 68 ± 14 msec < tachycardia CL; the inner limits were 56 ± 18 msec and 90 ± 24 msec < tachycardia CL for RBBB and LBBB, respectively (both P < 0.05). Dissipation could not be achieved in group 2 (4 RBBB and 1 LBBB) due to CL-dependent bundle branch block and/or local ventricular refractoriness. Conclusion: During SVT, functional bundle branch block due to “linking” often can be dissipated by timely PVB delivered from the right ventricular apex within a narrow zone of the tachycardia CL. Our findings suggest that the dissipation zone is affected by the pattern of functional bundle branch block relative to the site of PVB delivery.

The purpose of this study was to assess monocular and binocular distance perception, and stereoacuity, in individuals with mild traumatic brain injury (mTBI) who reported the symptom of "poor depth perception";Ten patients with mTBI were tested and compared with ten visually-normal asymptomatic individuals in the following areas: perceived distance, stereoacuity at distance (3 meters) and near (40 cm), and a 9-item 5-point rating-scale questionnaire related to distance perception. Distance perception was assessed under monocular and binocular viewing conditions in both clustered and isolated static environments. Magnitude estimation was used to obtain the distance perception response function of physical versus perceived distance using common objects positioned at distances of 0.77 to 12.84 meters.The mean distance perception response function slopes were not significantly different in the two groups for any of the test conditions. Stereoacuity (sec arc) was slightly reduced at both near and distance in the individuals with mTBI (36 ± 24.58 and 84 ± 68.34, respectively) as compared with the normal subjects (20 ± 0 and 51 ± 9.93, respectively). The mTBI group mean symptom score was 3.24 ± 0.26 indicating a moderate problematic level;Similarity of the mean distance response functions in the mTBI group under monocular and binocular viewing conditions suggested that their misperception of distance was not due to a "binocular vergence" problem. Similarly, the slightly reduced stereoacuity in the mTBI group was not sufficient to explain their symptom of "poor depth perception." Thus, it is speculated that this problem reflects a higher-level cortical perceptual phenomenon related to diffuse brain damage in areas dealing with visuo-spatial mapping.

Evaluation of the efficacy of molecular treatment strategies for lymphatic vascular insufficiency requires a suitable preclinical animal model. Ideally, the model should closely replicate the untreated human disease in its pathogenesis and pathological expression.We have undertaken a study of the time course of the development and resolution of acquired, experimental lymphedema and of its responses to vascular endothelial growth factor (VEGF)-C lymphangiogenesis in the mouse tail model.We provoked post-surgical lymphedema in the mouse tail model and assessed the effects of exogenously administered human recombinant VEGF-C. Quantitative assessment of immune traffic function was performed through sequential in vivo bioluminescent imaging.In untreated lymphedema, tail edema was sustained until day 21. Exogenous administration of human recombinant VEGF-C produced a significant decrease in volume. Untreated lymphedema in the mouse tail model was characterized by the presence of dilated cutaneous lymphatics, marked acute inflammatory changes, and hypercellularity; VEGF-C produced a substantial reversion to the normal pattern, with notable regression in the size and number of cutaneous lymphatic vessels that express lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). In vivo imaging confirmed the presence of an impairment of immune traffic in lymphedema that was ameliorated after VEGF-C administration.The post-surgical murine tail model of lymphedema closely simulates attributes of human lymphedema and provides the requisite sensitivity to detect therapeutically induced functional and structural alterations. It can, therefore, be used as an investigative platform to assess mechanisms of disease and its responses to candidate therapies, such as therapeutic lymphangiogenesis.

Background Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. Methods and Findings We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. Conclusions We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency., Editors' Summary Background. Lymphedema is the term used to describe the swelling that can occur after surgery, especially after axillary lymph node dissection for breast cancer, when the lymph vessels that carry protein-rich interstitial fluid from the tissues to the heart are damaged. Lymphedema can be extremely unpleasant and is very hard to treat; treatments that are currently used include those aimed to help massage the flow of lymph back to the chest. Lymphedema seems to be more than just accumulation of lymph, however, as changes also occur in the tissue surrounding the damaged lymph vessels. Currently, very little is known at the most basic level about what exactly these changes are, although they appear to be similar to an inflammatory process. One way of studying such a disease process in humans is to make an animal model that mimics the human condition and study the changes that occur there. For lymphedema, such a model can be made in the mouse tail by cutting lymph vessels there. Why Was This Study Done? The authors wanted to look closely at what happens in the tissues surrounding damaged lymph vessels to try to understand better what these changes are. They also wanted to study the movement of the cells that are normally carried in the lymph. What Did the Researchers Do and Find? The mouse model that the authors developed closely simulates the characteristics of human acquired lymphedema. In the mouse tails that had had their lymph vessels damaged, the authors were able to show that the tails were swollen compared with those of normal animals and of animals that hadhad sham (pretend) surgery. In the animals with lymphedema, many small lymph vessels were seen, as the lymph was unable to flow away normally. The area affected by the lymphedema had the appearance often seen in inflamed tissue, and analysis of genes from the same area to see how active, or “expressed,” they were showed changes that are often seen in, for example, acute inflammation and wound healing. The authors also showed that when these animals were injected with immune cells marked with a light marker, they were less able to remove the cells from the circulation. What Do These Findings Mean? These results show that the response to lymph stagnation is complex, but looks similar to that seen in acute inflammation. These results and this model may be useful in suggesting, and at a later date perhaps testing, treatments for lymphedema. One difference, however, between this mouse model and the condition in humans is that whereas lymphedema in humans is a rather chronic condition, here the researchers were only able to look at the changes over a short period of time. In a related Perspective article, Peter Carmeliet and colleagues further discuss the clinical relevance of these findings ( http://dx.doi.org/10.1371/journal.pmed.0030264). Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030254. • The National Cancer Institute has information for patients and health professionals on lymphedema • Cancerbackup is a United Kingdom cancer information service with information on many aspects of cancer, including lymphedema • The Lymphatic Research Foundation Description has information on lymphatic system research, Rockson and colleagues characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging, histopathological examination, and transcriptional profiling.

Myotonic dystrophy1 (DM1) is an autosomal dominant, multi-system disorder resulting from a CTG repeat expansion located in the 3' untranslated region of DMPK and immediately in the 5' of SIX5. Skeletal muscle, heart and smooth muscle are prominently affected in DM1. Endocrine abnormalities, gonadal atrophy, brain, skin, skeletal, immune and respiratory defects are also features of the disorder. Both DMPK and SIX5 levels are decreased in DM1 patients. Importantly, expression of mutant mRNAs encoding expanded CUG repeats has been shown to alter the activity of CUG repeat binding proteins in DM1. Mouse models have demonstrated that decreased levels of Dmpk, Six5 and the expression of expanded CUG repeats independently contribute to the development of DM1 pathology. However, an important gap in these studies is a lack of clear understanding of the expression pattern of Dmpk. We demonstrate that Dmpk mRNA is expressed in a range of adult mouse tissues that show pathology in DM1 including skeletal muscle, heart, smooth muscle, bone, testis, pituitary, brain, eye, skin, thymus and lung. Thus DMPK loss or CUG repeat expansion could contribute to DM1 pathology to these tissues. Dmpk mRNA is not detected in the ovary, pancreas or kidney. Significantly, Dmpk mRNA is expressed in the intestinal epithelium, cartilage and liver, which have not been reported to show consistent abnormalities in Dmpk(-/-) mice or in transgenic animals expressing CUG repeats. Taken together these data suggest that Dmpk loss or CUG repeat expression per se may not be sufficient to initiate pathology and are consistent with the hypothesis that coexpression of specific CUG repeat binding proteins with the mutant Dmpk mRNA or deregulation of genes such as Six5 that flank the CTG repeat tract may be necessary for DM1 to manifest.

The objective of this study was to characterize the autonomic effects of 2 interventions, head-up tilt and isoproterenol infusion, which alter autonomic balance by different mechanisms but produce the same RR intervals. We compared the effect of head-up tilt with the effect of isoproterenol on autonomic balance as measured by power spectral analysis of RR variability. Fifteen normal subjects had baseline measurements and then underwent head-up tilt. After return to baseline supine values, isoproterenol was infused at a rate of 1 microgram/min (low-dose isoproterenol), which was then increased to 2.1 +/- 0.5 microgram/min (high-dose isoproterenol). All subjects underwent a second tilt during high-dose isoproterenol, and 9 subjects completed this second tilt study. During the experiment, normal RR intervals were recorded and 5-minute segments were used to calculate power spectra. High-frequency (HF) power (0.15 to 0.40 Hz) was used as a measure of vagal activity. The effects of head-up tilt were compared with the effects of low-dose isoproterenol. Despite nearly identical mean RR intervals (784 ms with tilt vs 792 ms with low-dose isoproterenol, p = NS), there was significantly (p0.05) less HF power during head-up tilt in the drug-free state (172 ms2) than during low-dose isoproterenol in the supine position (307 ms2). A second head-up tilt was performed during the infusion of high-dose isoproterenol. During high-dose isoproterenol, tilt caused a decrease in RR intervals (from 573 to 491 ms; p0.01) and a decrease in HF power (from 68 to 28 ms2; p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The accuracy and reproducibility of caliper and cinevideodensitometric measurements of coronary stenotic dimensions were compared in radiographic phantom models and in coronary arteriograms of 28 patients undergoing coronary angioplasty. Projected, single-plane coronary cine frames were analyzed by a computer-assisted videodensitometric method, which measures stenotic cross-sectional area without assumptions about lesion geometry. The accuracy (2.4%) and precision (+/- 1.9%) of cinevideodensitometry for measuring percent area stenosis in Plexiglas models of eccentric stenotic lesions was superior to the accuracy (24.7%) and precision (+/- 5.4%) of caliper measurements. Interobserver variability was significantly (p less than 0.05) better for cinevideodensitometric (r = 0.98; SEE = 6.4%) than for caliper measurements (r = 0.87; SEE = 13.1%). After angioplasty, percent diameter stenosis measured by calipers fell from 70 +/- 12% to 30 +/- 15%. Mean percent area reduction measured by cinevideodensitometry fell from 89.1 +/- 8% to 40.1 +/- 22% and stenotic area increased five-fold, from 0.59 +/- 0.5 to 3.47 +/- 1.6 mm2. Pre and post PTCA gradients did not correlate with lesion dimensions. Cinevideodensitometric measurements of absolute stenotic dimensions were more reproducible than relative measurements expressed as a percentage, due to the tapered caliber of normal arterial segments. Thus, cinevideodensitometric measurements were more accurate and reproducible than caliper measurements. The angiographic effects of coronary angioplasty are best measured by cinevideodensitometry, because residual lesions post PTCA are often eccentric, have indistinct margins, and are better characterized by changes in area than by changes in diameter.