Search

Aims Arthroplasty has become increasingly popular to treat end-stage ankle arthritis. Iatrogenic posterior neurovascular and tendinous injury have been described from saw cuts. However, it is hypothesized that posterior ankle structures could be damaged by inserting tibial guide pins too deeply and be a potential cause of residual hindfoot pain. Methods The preparation steps for ankle arthroplasty were performed using the Infinity total ankle system in five right-sided cadaveric ankles. All tibial guide pins were intentionally inserted past the posterior tibial cortex for assessment. All posterior ankles were subsequently dissected, with the primary endpoint being the presence of direct contact between the structure and pin. Results All pin locations confer a risk of damaging posterior ankle structures, with all posterior ankle structures except the flexor hallucis longus tendon being contacted by at least one pin. Centrally-aligned transcortical pins were more likely to contact posteromedial neurovascular structures. Conclusion These findings support our hypothesis that tibial guide pins pose a considerable risk of contacting and potentially damaging posterior ankle structures during ankle arthroplasty. This study is the first of its kind to assess this risk in the Infinity total ankle system. Cite this article: Bone Jt Open 2021;2(7):503–508.

Objective: Although there is evidence of effective stigma reduction by various psychological and educational interventions, the mechanisms of change remain unclear. In this article, we examine hypothesized processes that might have mediated reductions in stigma observed among Asian men who had received in mental health promotion interventions in Greater Toronto Area, Canada. Method: Our sample consisted of 495 Asian men, who received either acceptance and commitment therapy (ACT; n = 133), contact-based empowerment education (CEE; n = 149), combination of ACT and CEE ( n = 152), or psychoeducation ( n = 61). Group differences on intervention outcomes, including stigmatizing attitudes (Community Attitudes toward the Mentally Ill), internalized stigma (Internalized Stigma of Mental Illness), valued living (Valued Living Questionnaire), and attitudes to engage in social change (Social Justice Scale) were hypothesized to be due to the impact of the different interventions and mediated by changes in specific underlying psychological processes. These process-related changes were modelled using measures of mindfulness (Freiburg Mindfulness Inventory), psychological flexibility (Acceptance and Action Questionnaire version II), and empowerment (Empowerment Scale [ES]). Their pre- and post changes were analyzed with repeated measures analysis of variance, and mediational analyses were performed. Results: Findings from mediational analyses suggest that empowerment (ES) mediated a significant portion of the effects observed in reduction in stigmatizing attitudes and internalized stigma across intervention groups ( t = 3.67 to 3.78 for CEE groups, and t = 4.32 to 4.56 for ACT groups). For the ACT groups, reduction in internalized stigma might also have been partly mediated by psychological flexibility, an intervention-specific psychological process. Conclusions: Results from the current study suggest that different stigma reduction interventions may be mediated by increased empowerment as a common mechanism of change, while intervention-specific mechanism of change, improved psychological flexibility through ACT, may also contribute to improvement in internalized stigma.

Thyroid hormones (TH) are essential for an adequate development and kidney maturity. The dysfunction of thyroid causes striking changes in glomerular and tubular capacities and electrolyte and water homeostasis. Hypothyroidism is affiliated with a decline in glomerular filtration, hyponatremia, and a modification of the capacity for water extraction. Since various renal function derangements occur in hypothyroidism, therefore, present study has been intended to determine the various parameters (urea, creatinine and uric acid) related to renal function in hypothyroid patients and correlation of these parameters with thyroid hormones (T3, T4, TSH). The study was conducted on 200 hypothyroidisms. Age and sex matched healthy euthyroids were selected for the study. Serum was taken from each patient and control and was analyzed for T3 by competitive analog-based immunoassay, T4 by competitive analog-based immunoassay, TSH by 2 site chemiluminescent immunometric assay, creatinine by modified Jaffe’s method, urea by urease method and uric acid by uricase method respectively. A total number of 300 cases that includes 200 hypothyroid patients (25% males and 75% females) and 100 controls (42% males and 58% females) were examined. The mean level of serum T3 (1.968 ± 0.1195 pg/ml), serum T4 (1.0152 ± 0.1235 pg/ml), serum urea (33 ± 5.570mg/dl) of hypothyroids were significantly lower as compared to mean level of serum T3 (3.704 ± 0.1699 pg/ml), serum T4 (1.5764 ± 0.16230 pg/ml) and serum urea (35.12 ± 3.710mg/dl) of euthyroids. The mean level of serum TSH (8.928 ± 0.9589µIU/ml) serum Creatinine (2.192 ± 0.2566mg/dl) and serum uric acid (4.224 ± 0.6554mg/dl) of hypothyroids were significantly higher as compared to mean level of serum TSH (3.06 ± 0.4110 µIU/ml), serum Creatinine (0.852 ± 0.1396 mg/dl) and serum uric acid (3.772 ± 0.2975 mg/dl) of euthyroids. Hypothyroids serum T3 significantly correlated with positive person serum uric acid (r = 0.343). Hypot

We develop fast and accurate algorithms for evaluating √x 2 +y 2 for two floating-point numbers x and y . Library functions that perform this computation are generally named hypot(x,y). We compare five approaches that we will develop in this article to the current resident library function that is delivered with Julia 1.1 and to the code that has been distributed with the C math library for decades. We will investigate the accuracy of our algorithms by simulation.

The purpose of this study was to investigate the influence of perceived personal responsibility for an acquired ABI (ABI) on shame, and whether self-compassion moderates this relationship. We hypothesized that people who perceived themselves to be responsible for their injury would have high levels of shame and poorer recovery outcomes.A mixed-methods design was employed using both standardized measures and a series of open questions.66 participants with ABI were included in the analysis. Data were analyzed using descriptive statistics, correlations, multiple regression, and thematic analysis.Significant relationships were found between self-compassion, shame, anxiety, and depression, but perceived responsibility for ABI was not correlated with any examined variables. Due to issues with the measurement of responsibility, it was not possible to complete all proposed forms of analysis. The thematic analysis revealed the ways participants' injuries affected their perceived level of functioning, its consequences for sense of self, shame, and self-compassion.This study concluded that people with ABI might experience shame with respect to the injury's impact on functioning. Study limitations and implications for providing therapeutic interventions such as Compassion Focused Therapy and Acceptance and Commitment Therapy are discussed.

Background: Social identity theory proposes that people define themselves in terms of the social groups they belong to or aspire to belong to. Tobacco smoking and alcohol use in men have been hypot...

Distance perception for mobile agents is of great importance for safe navigation in unknown environments. Traditional methods make use of analytical solutions. Yet, according to some research hypothesis, distance perception is not the result of mathematical calculations, but an emergent consequence of an association process, where visual and tactile information acquire a central role. Designing models closer to natural cognition poses paramount challenges to artificial intelligence (AI), which call for a review of some of the foundations of current methods. Our work is framed in the embodied cognition paradigm, which highlights the importance of the body for the development of cognitive processes. We provide theoretical grounds and empirical evidence for an artificial account of distance perception through a multimodal association process. By learning multimodal sensorimotor schemes, an agent is capable of perceiving affordances related to distance perception without any non-body-based geometric knowledge. We let an agent interact with an environment cluttered with objects, while learning multimodal sensorimotor associations. The learned spatial relations are thoroughly characterized to show how the model depends on the agent’s specific sensorimotor capabilities. The system is tested in a passability experiment and a navigation task, showing the agent anticipates undesired situations using the learned model predictions.

Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight.Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal-epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis.Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups.Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively.

Humanity has used the power of falling water for centuries to produce electrical energy, but there have been no significant changes in technology. Marine Energy has received an explosive development. Traditional technologies are passive and have low efficiency. It is not possible to use the effect of falling water in the ocean. The chapter considers the technology, which allows to convert not only the kinetic energy of a moving horizontal flow, but also the potential energy of water hammer in a combination of pressure drop between layers of water that have different hydrodynamic characteristics. This is a high efficiency due to the use of the Pitot-Prandtl tube principle and Bernoulli’s law and in combination with the effect of raising the water of the hydraulic ram. The calculations are based on computational fluid dynamics (CFD) methods. It is known that 94% of incoming solar energy is converted into underwater currents and only 6% - on the surface. Therefore, the proposed technology can be highly competitive in relation for example to Orbital Marine Power (OMP) project and another known offshore wind and wave power plants which convert only the kinetic energy of the surface air and sea currents.

Background Although beta blockers could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. This study sought to determine the relationship between type of beta blocker and incidence of hypoglycemia and mortality in hospitalized patients. Methods We retrospectively identified non-critically ill hospitalized insulin requiring patients who were undergoing bedside glucose monitoring and received either carvedilol or a selective beta blocker (metoprolol or atenolol). Patients receiving other beta blockers were excluded. Hypoglycemia was defined as any glucose 1day) or throughout hospitalization (HypoT) and any glucose severe). Results There were 1020 patients on carvedilol, 886 on selective beta blockers, and 10,216 on no beta blocker at admission. After controlling for other variables, the odds of Hypo1day, HypoT and Hyposevere were higher for carvedilol and selective beta blocker recipients than non-recipients, but only in basal insulin nonusers. The odds of Hypo1day (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.28, 3.09, p = 0.0002) and HypoT (OR 1.38, 95% CI 1.02, 1.86, p = 0.03) but not Hyposevere (OR 1.90, 95% CI 0.90, 4.02, p = 0.09) were greater for selective beta blocker vs. carvedilol recipients in basal insulin nonusers. Hypo1day, HypoT, and Hyposevere were all associated with increased mortality in adjusted models among non-beta blocker and selective beta blocker recipients, but not among carvedilol recipients. Conclusions Beta blocker use is associated with increased odds of hypoglycemia among hospitalized patients not requiring basal insulin, and odds are greater for selective beta blockers than for carvedilol. The odds of hypoglycemia-associated mortality are increased with selective beta blocker use or nonusers but not in carvedilol users, warranting further study.

Hypothyroidism is considered a cardiac risk factor, but there is controversial evidence about its effects on coronary disease. The aim of this work was to evaluate the influence of hypothyroidism in rat hearts exposed to 2 degrees of stunning due to ischemia and reperfusion (I/R) as well as the underlying mechanisms. Hypothyroid (HypoT) rats were obtained by drinking 0.02% methimazole during 15 days. Isolated hearts were perfused and introduced in a flow calorimeter to measure contractile performance (P), total heat rate (Ht), and muscle economy (P/Ht). Hearts were exposed to 2 models of I/R, moderate and severe (respectively 20 or 30 minutes I/45 minutes R). Moreover, free cytosolic and mitochondrial calcium changes were measured by confocal fluorometry on cardiomyocytes. Comparison to euthyroid (EuT) hearts was done. Hypothyroidism was cardioprotective, but HypoT hearts were more sensitive than EuT hearts to the preischemic blockade of mitochondrial transporters mNCX and mKATPchannels. Moreover, the postischemic recovery of P and P/Ht in HypoT hearts was strongly reduced by inhibition of the cellular pathways of PI3K/Akt and protein kinase C (PKC), and it was increased by nitric oxide synthase (NOS) inhibition. However, physiological concentrations of adrenaline reduced the cardioprotection of HypoT, but oral treatment with 20 mg/kg/day carvedilol prevented it. Results show that hypothyroidism reduces the mitochondrial Ca2+overload during I/R by mKATPchannel activation and Ca2+extrusion through mNCX, while the PI3K/Akt and PKC pathways are involved in that cardioprotection. Contrarily, NOS activation and adrenaline blunt such cardioprotection, but carvedilol prevented the adrenergic dysfunction. These results would explain why hypothyroidism is a clinical risk factor in angor patients under adrenergic exacerbation but reduced the incidence of acute episodes of coronary syndrome in hospitalized patients. Results suggest that a treatment with carvedilol could be a potential therapeutic agent to prevent cardiac postischemic dysfunction in hypothyroid patients.

The intrinsically photosensitive retinal ganglion cells are the main conduit of the light signal emanating from the retina to the biological clock located in the suprachiasmatic nuclei of the hypothalamus. Lighting manufacturers are developing white light sources that are devoid of wavelengths around 480 nm (“cyan gap”) to reduce their impact on the circadian system. The present study was designed to investigate whether exposure to a “cyan-gap,” 3000 K white light source, spectrally tuned to reduce radiant power between 475 and 495 nm (reducing stimulation of the melanopsin-containing photoreceptor), would suppress melatonin less than a conventional 3000 K light source. The study’s 2 phases employed a within-subjects experimental design involving the same 16 adult participants. In Phase 1, participants were exposed for 1 h to 3 experimental conditions over the course of 3 consecutive weeks: 1) dim light control (1,12 = 9.1, p < 0.05, ηp² = 0.43) and exposure duration ( F1,12 = 47.7, p < 0.05, ηp² = 0.80) but there was no significant main effect of spectrum ( F1,12 = 0.16, p > 0.05, ηp² = 0.01). There were no significant interactions with spectrum. Contrary to our model predictions, our results showed that short-term exposures (≤ 1 h) to “cyan-gap” light sources suppressed melatonin similarly to conventional light sources of the same CCT and photopic illuminance at the eyes.

Background: Functional outcomes are improved when AIS patients receive faster treatment. The first medical contact for many AIS patients is with emergency medical services (EMS) providers. We hypothesize that AIS treatment is faster when EMS providers suspect stroke. Methods: We performed a retrospective analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a comprehensive study of stroke patients in a large geographical area with 1.3 million inhabitants whose demographics are representative of the United States. We compared AIS patients age ≥18 years transported by EMS in 2015 with an EMS impression of “stroke” or “weakness/numbness” to those with other EMS impressions. Primary outcome was thrombolysis rate, and secondary outcomes were times from EMS scene arrival to ED arrival, CT, and treatment and times from ED arrival to CT and treatment. Chi-square and Mann-Whitney U-tests were used to compare treatment rates and times, respectively. Logistic regression (for rates) and median regression (for times) adjusted for NIHSS, GCS, age, sex, race, and prior stroke history. Results: Among 2,486 confirmed AIS patients from 1/1/2015-12/31/2015, 868 were transported by EMS, including 595 (69%) with EMS suspected stroke. Compared to EMS non-suspected strokes, patients with EMS suspected stroke patients were more likely to receive thrombolysis (18% vs 8%; OR 2.67, 95% CI 1.63-4.47) and had faster prehospital transport (30 vs 32 min, p=0.02), ED arrival to CT (27 vs 46 min, p Conclusions: In a large population-based study, EMS stroke identification is associated with a higher rate of and faster thrombolysis. Efforts to increase accuracy of EMS stroke identification is likely to have significant clinical impact by shortening treatment times.

(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: Six dogs with HypoT and healthy age-matched control dogs (n = 23) were vaccinated against CPV with a modified-live vaccine. Hemagglutination inhibition was used to measure antibodies on days 0, 7, and 28. The comparison of the vaccination response of dogs with HypoT and healthy dogs were performed with univariate analysis. (3) Results: Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HypoT (6/6, 95% CI: 55.7–100) and in 100% of healthy dogs (23/23, 95% CI: 83.1–100.0). A ≥4-fold titer increase was observed in none of the dogs with HypoT and in 4.3% of the healthy dogs (1/23, CI95%: &lt, 0.01–22.7). Mild vaccine-associated adverse events (VAAEs) were detected in 33.3% of the dogs with HypoT (2/6, 95% CI: 9.3–70.4) and in 43.5% (10/23, 95% CI: 25.6–63.2) of the healthy dogs. (4) Conclusions: There was neither a significant difference in the dogs’ pre-vaccination antibodies (p = 1.000), or vaccination response (p = 0.735), nor in the occurrence of post-vaccination VAAEs (p = 0.798). The vaccination response in dogs with levothyroxine-treated HypoT seems to be similar to that of healthy dogs.

Background: Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. Methods: We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at six academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10ml/min/1.73m2 at a 5% significance level. Findings: Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/min/1.73m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1-year after surgery. The change in mGFR 1-year after surgery was -6.6 ml/min/1.73m2 in the hypothermia group and -7.8 mL/min/1.73m2 in the control group (mean difference 1.2 mL/min/1.73m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 mL/min/1.73m2; mean difference 0.5 mL/min/1.73m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. Interpretation: Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.

Dear Editor,In the case series of 16 Steatoda nobilis envenomations by Dunbar et al. [1] they report a variety of symptoms and signs, including as debilitating pain, tremors, fatigue, nausea, hypot...

Objective: The cAMP second messenger system, a major stress-response pathway, plays essential roles in normal cardiovascular functions and in pathogenesis of heart diseases. Here, we test the hypothesis that the Epac1 (exchange protein directly activated by cAMP 1) acts as a major downstream effector of cAMP signaling to promote atherogenesis and represents a novel therapeutic target. Approach and Results: To ascertain Epac1’s function in atherosclerosis development, a triple knockout mouse model ( LTe ) was generated by crossing Epac1 −/− mice with atherosclerosis-prone LDb mice lacking both Ldlr and Apobec1 . Deletion of Epac1 led to a significant reduction of atherosclerotic lesion formation as measured by postmortem staining, accompanied by attenuated macrophage/foam cell infiltrations within atherosclerotic plaques as determined by immunofluorescence staining in LTe animals compared with LDb littermates. Primary bone marrow–derived macrophages were isolated from Epac1-null and wild-type mice to investigate the role of Epac1 in lipid uptake and foam cell formation. ox-LDLs (oxidized low-density lipoproteins) stimulation of bone marrow–derived macrophages led to elevated intracellular cAMP and Epac1 levels, whereas an Epac-specific agonist, increased lipid accumulation in wild-type, but not Epac1-null, bone marrow–derived macrophages. Mechanistically, Epac1 acts through PKC (protein kinase C) to upregulate LOX-1 (ox-LDL receptor 1), a major scavenger receptor for ox-LDL uptake, exerting a feedforward mechanism with ox-LDL to increase lipid uptake and propel foam cell formation and atherogenesis. Conclusions: Our study demonstrates a fundamental role of cAMP/Epac1 signaling in vascular remodeling by promoting ox-LDL uptake and foam cell formation during atherosclerosis lesion development. Therefore, Epac1 represents a promising, unexplored therapeutic target for atherosclerosis.

Introduction: Transcatheter aortic valve implantation (TAVI) is a procedure that alters dramatically the hemodynamics in patients with severe aortic valve stenosis who undergo this procedure. Hypothesis: We investigated the hypothesis that arterial properties and hemodynamics are affected immediately after TAVI as well as in the long-term. Methods: We enrolled 90 patients (mean age 80.2 ± 8.1 years, 50% males) with severe symptomatic aortic stenosis undergoing TAVI. Carotid-femoral and brachial-ankle pulse wave velocity (cfPWV and baPWV) were used for the assessment of arterial stiffness. Augmentation index corrected for heart rate (AIx@75) and subendocardial viability ratio (SEVR) were measured non-invasively. Measurements were conducted at baseline, after the procedure (during hospitalization) and at 1 year. Results: Acutely after TAVI we observed a statistically significant increase in arterial stiffness (7.5 ± 1.5 m/s vs 8.4 ± 1.9 m/s, p=0.001 for cfPWV and 1,773 ± 459 cm/s vs 2,383 ± 645 cm/s, p Conclusions: In conclusion, shortly after TAVI the aorta exhibits a "stiffer" behavior in response to the acute change in hemodynamics, which settles in the long term. Our findings further elucidate the hemodynamic consequences of TAVI and may entail a prognostic role in this growing population.

Introduction: Presence of Chronic Total Occlusion (CTO) in patients with Acute Myocardial Infarction (AMI) undergoing Percutaneous Coronary Intervention (PCI) has not been studied previously. Hypothesis: To study in-hospital mortality & resource utilization of AMI patients undergoing PCI associated with presence of CTO. Methods: We queried National Inpatient Sample from October 2015 - December 2017 using ICD 10 codes to identify patients over 18 years of age who underwent PCI & had AMI with presence or absence of CTO. SAS 9.4 was used for univariate and multivariate analysis. Propensity score matching was performed to matched CTO vs Non-CTO group’s baseline characteristics & Elixhauser comorbidities with Absolute standardized difference of 10% as matching limit. Results: A total of 576760 patients were identified who underwent PCI with AMI, out of which 525535 (91.12%) had no CTO while 51225(8.8%) had CTO. Each matched group contains 51210 patients. The In-hospital mortality was significantly higher in AMI PCI patients with CTO compared to Non-CTO (4.7% vs 3%, p p =0.001) and less percentage of patients were discharged to home (78.8% vs 81.1%, p p Conclusions: Analysis of this large database of patients undergoing PCI with AMI suggests that presence of CTO results in higher In-hospital mortality, with longer hospital stay & higher cost. Future observational studies should be directed towards CTO based outcomes in AMI patients undergoing PCI.

Introduction: CD34 +ve Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). Hypothesis: Canagliflozin, an SGLT2 inhibitor when added to other oral antidiabetic medication such Metformin, Insulin, GLP1-agonists, DPP-IV inhibitor, or sulfonylureas, may improve the cardiovascular risk by improving CD34+ EPCs function such as migration, colony formation and maturation towards endothelium. Methods: 29 subjects were enrolled in this 16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo. T2DM (30-70 years old), HbA1c of 6.5-10%, and all stages of CKD were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0, 8, and 16. A mixed model regression analysis was done with a p-value Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure. There was a reduction in blood glucose level (p=0.0047) and HbA1c (p=0.03). There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin. There is also an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA (p=0.049), VEGF receptor KDR (p=0.13), PECAM-1, a mature endothelial marker was also upregulated (p=0.002) and NOS3 (or eNOS) was also upregulated. There were no significant changes in CD34+ numbers by direct counting and parameters tested. We also tested for serum ketones bodies and found no difference at the dose tested. Data on urine podocyte specific exosome is pending Conclusions: Our study indicates that Canagliflozin improves several components of ECF by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes.

Introduction: Studies have shown decrease rates of restenosis and target lesion revascularization (TLR) with drug eluting balloon (DEB) in diabetic patients with critical limb ischemia (CLI). Hypothesis: The aim of this meta-analysis to compare the efficacy of DEB versus Percutaneous transluminal angioplasty (PTA) below the knee peripheral intervention. Methods: Electronic databases including MEDLINE, ClinicalTrials.gov and the Cochrane Library were searched for all randomized controlled trials (RCTs) published until April 2020 comparing outcomes of DEB vs PTA in patients with CLI below the knee. End points were major amputation, major adverse events (MAEs), all-cause mortality, target lesion revascularization (TLR), myocardial infarction, and cerebrovascular accidents (CVA). The risk ratio (RR) with 95% confidence interval (CI) were computed and p Results: A total of 4 RCTs (n=655) were included in the final analysis. There were no differences of major amputation (RR: 1.30; CI: 0.68-2.46; p=0.43), MAEs (RR: 0.86; CI: 0.60-1.23; p=0.41), all-cause mortality (RR: 0.91; CI: 0.69-1.19; p=0.48), TLR (RR: 0.65; CI: 0.30-1.44; p=0.29), MI (RR: 1.71; CI: 0.57-5.14; p=0.34) and CVA (RR: 0.66; CI: 0.19-2.26; p=0.50) between the 2 groups [Figure 1]. Conclusions: There were no significant differences of major amputation and TLR for DEB versus PTA . Major adverse cardiac, cerebrovascular events and all-cause mortality were not statistically different for drug coated balloon versus PTA in the management of below knee critical limb ischemia. Further studies needed to confirm these findings.

Introduction: Idiopathic ventricular fibrillation (IVF) including Brugada syndrome (BS) is one of causes of cardiac arrest without prior overt cardiac dysfunction. Hypothesis: We assessed the hypothesis that patents of IVF had favor outcomes than those of non-IVF after cardiac arrest treated with targeted temperature management (TTM). Methods: Patients who were treated with TTM after cardiac arrest between 2000 and 2019 were enrolled in the study. Patients were divided into 2 groups according to whether the patients were diagnosed as IVF or not. The patients treated with TTM were routinely performed coronary angiography. Results: Among the study patients (N = 306), 35 (11%) patients were IVF and 7 were BS. The patients of the IVF group were significantly younger (median 53 y vs. 64 y) than those of the non-IVF group. The prevalence of initial rhythm was shockable (69% vs. 47%, P = 0.02) was significantly higher in the patients of the IVF group than those of the non-IVF group. Among the patients in the non-IVF group, 114 patients (42%) were diagnosed as acute coronary syndrome and 93 patients (35%) were treated with coronary revascularization. The prevalence of male sex (77% vs 74%, P = 0.70) and witnessed to arrest (80% vs. 81%, P = 0.87), and low-flow time (29 min vs. 38 min [20 - 43 min vs. 21 - 52 min, P = 0.15]) were similar between the 2 groups. The prevalence of performing extracorporeal resuscitation (9% s 43%, P < 0.001) were lower in the patients of the IVF group. The 8-y survival rate were shown in the figure. All of the BS patients were witnessed arrest and were discharged without severe neurological deficit. The IVF as the cause of arrest was independently associated with 8-y survival. Conclusions: The patients of IVF had favor outcomes than those of non-VF. One of causes may be the lower prevalence of requiring extracorporeal circulatory support due to less cardiac dysfunction. The patients of BS had the tendency toward higher survival rate than those of non-BS IVF patients.

Background: Internal carotid artery (ICA) injuries represent a rare, potentially fatal complication of endoscopic endonasal skull base surgery (EESBS). The use of adenosine to induce transient hypotension and facilitate management of high-flow, high-pressure arterial lesions has been well-documented in neuro-endovascular literature. A similar setting in which adenosine-induced hypotension may prove beneficial is during the management of major vascular injury encountered during EESBS. Methods: A case of ICA injury and subsequent repair during EESBS is presented. Results: A 74-year-old female underwent endoscopic transsphenoidal resection for a recurrent pituitary adenoma. During suprasellar resection, the right cavernous ICA was inadvertently injured resulting in brisk bleeding. Immediate vascular tamponade was applied, and a crushed muscle graft was obtained. Two intravenous doses of adenosine were administered in quick succession to produce transient hypotension and facilitate repair of the injury with the graft. Neurovascular imaging revealed a small pseudoaneurysm which remained stable throughout the postoperative course. The patient underwent definitive stent embolization of the pseudoaneurysm 1 month following discharge. Conclusion: Prompt repair of ICA injury during EESBS is crucial, but often limited by poor visualization. Adenosine-induced hypotension has demonstrated great efficacy as an adjuvant in neurovascular clipping of intracranial aneurysms and remains a valuable tool for the endoscopic skull-base surgeon as well. In cases with high risk for ICA injury, adenosine should be readily available.

We describe a rare case of functioning gonadotropins-producing pediatric adenoma immunostaining positively for FSH and focally for TSH causing central precocious puberty associated to central hypothyroidism in a 6 year-old girl.Clinical evaluation revealed precocious puberty, as confirmed by hormonal determination with elevated FSH and estradiol, while central hypothyroidism was biochemically diagnosed by a low fT4 and normal TSH. Head MRI showed the presence of a hyperintense pituitary lesion. The patient successfully underwent transsphenoidal endoscopic resection of the pituitary macroadenoma.Pathologic evaluation of the tissue resected at surgery confirmed the diagnosis of pituitary adenoma with positive immunohistochemistry for FSH and focally for TSH in a mixed pattern. Ten months after surgery, there were no neurological signs and symptoms. Postoperative head MRI showed no abnormalities and no evidence of tumor regrowth.Early and accurate diagnosis, multidisciplinary approach and close follow up are crucial factors for the favorable outcome.

Background: Bone bruises observed on magnetic resonance imaging (MRI) after an anterior cruciate ligament (ACL) injury could provide significant information about ACL injury mechanisms. Purpose/Hypothesis: The purpose of this study was to investigate common bone bruise patterns after an ACL injury. It was hypothesized that the most common bone bruise distribution pattern would be only the lateral side of both the femur and tibia. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Knee MRI scans of patients who underwent acute ACL reconstruction from August 2016 to August 2018 at our institution were selected. Imaging sequences in the sagittal and coronal planes were used for determining the bone bruise location in the lateral-medial and anterior-posterior directions, respectively. The presence, location, and intensity of bone bruises within specific compartments of the tibia and femur were documented. The relative bone bruise patterns of the tibia and femur were classified and analyzed. Results: A total of 207 patients (165 men, 42 women) met the inclusion criteria from a total of 4209 ACL reconstruction cases. The most common relative bone bruise pattern was located on only the lateral side of both the femur and the tibia (44.4%), followed by the lateral and medial sides of both the femur and tibia (29.0%). For the pattern found on the lateral and medial sides of both the femur and tibia, the bone bruises on only the lateral side of both the tibia and femur were more severe ( P < .001 and P < .001, respectively) and more anterior ( P < .001 and P < .001, respectively) than those on only the medial side. Conclusion: The most common relative bone bruise pattern observed was on only the lateral side of both the tibia and femur. Bone bruises on the lateral side were more severe than those on the medial side in patients with bone bruises on the lateral and medial sides of both the femur and tibia. Anterior translation of the tibia relative to the femur occurred during an ACL injury based on the location of bone bruises in the anterior-posterior direction.

Background: Heart rate variability (HRV) and pulse rate variability are indices of autonomic cardiac modulation. Increased pericardial fat is associated with worse cardiovascular outcomes. We hypothesized that progressive increases in pericardial fat volume and inflammation prospectively dampen HRV in hypercholesterolemic pigs. Methods: WT (wild type) or PCSK9 (proprotein convertase subtilisin-like/kexin type-9) gain-of-function Ossabaw mini-pigs were studied in vivo before and after 3 and 6 months of a normal diet (WT-normal diet, n=4; PCSK9-normal diet, n=6) or high-fat diet (HFD; WT-HFD, n=3; PCSK9-HFD, n=6). The arterial pulse waveform was obtained from an arterial telemetry transmitter to analyze HRV indices, including SD (SD of all pulse-to-pulse intervals over a single 5-minute period), root mean square of successive differences, proportion >50 ms of normal-to-normal R-R intervals, and the calculated ratio of low-to-high frequency distributions (low-frequency power/high-frequency power). Pericardial fat volumes were evaluated using multidetector computed tomography and its inflammation by gene expression of TNF (tumor necrosis factor)-α. Plasma lipid panel and norepinephrine level were also measured. Results: At diet completion, hypercholesterolemic PCSK9-HFD had significantly ( P 50 ms, high-frequency power, low-frequency power), and both HFD groups had higher sympathovagal balance (SD of all pulse-to-pulse intervals over a single 5-minute period/root mean square of successive differences, low-frequency power/high-frequency power) compared with normal diet. Pericardial fat volumes and LDL (low-density lipoprotein) cholesterol concentrations correlated inversely with HRV and directly with sympathovagal balance, while sympathovagal balance correlated directly with plasma norepinephrine. Pericardial fat TNF-α expression was upregulated in PCSK9-HFD, colocalized with nerve fibers, and correlated inversely with root mean square of successive differences and proportion >50 ms. Conclusions: Progressive pericardial fat expansion and inflammation are associated with a fall in HRV in Ossabaw mini-pigs, implying aggravated autonomic imbalance. Hence, pericardial fat accumulation is associated with alterations in HRV and the autonomic nervous system. Visual Overview: A visual overview is available for this article.

Introduction: Physical activity has been associated with a lower risk of diabetes but less is known about the association of steps per day (steps/d) and step intensity with incident diabetes. Hypothesis: We hypothesized an inverse association between both number of steps/d and time spent at a stepping rate corresponding to purposeful steps ( > 40 steps/min) with the risk of incident diabetes. Methods: We included 7247 participants free of diabetes at baseline in the prospective HCHS/SOL cohort of Latinos sampled from four communities in the United States. Steps/d and minutes per day (min/d) at a stepping rate > 40 steps/min were assessed at baseline with the Actical accelerometer (2008-2011), and incident diabetes was ascertained at a follow-up visit (2014-2017). The association of steps with incidence rates (per 1,000 person-years) of diabetes and incidence rate ratios (IRR) was estimated using Poisson regression, accounting for the sampling design and adjusted for age, ethnicity, gender, education, smoking status, alcohol intake, and accelerometer wear time. Results: The average age at baseline was 38 years (range 18 - 74 years) and 52% were female. Over a median of 5.9 years, 850 participants (9%) developed diabetes. The median step count was 7360 steps/d and the median minutes per day at a stepping rate of > 40 steps/min was 55 minutes. For each 1,000 step/d increment, the risk of diabetes was 5% lower (Table, IRR= 0.95(95% confidence interval (CI) 0.88, 1.02)). Compared to adults who engaged in 2,000 steps/d, those who engaged in 5,000 and 10,000 steps/d had a 13% and 26% lower risk of diabetes. The risk of diabetes was 5% lower (IRR=0.95 (95% CI 0.89, 1.00)) per 10 minute increase in time spent at a stepping rate > 40 steps/min. Compared to adults who spent 10 min/d at > 40 step/min, those who spent 30, 60, and 120 min/d had a 10%, 20%, and 32% lower risk of diabetes. Conclusion: The number of steps per day and time spent at a stepping rate that corresponds to purposeful steps are inversely associated with the risk of developing diabetes among adults.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is reported to be a predictor of cardiovascular disease (CD). NAFLD is probably associated with stroke in middle and old-aged patients. Hypothesis: In acute stroke patients aged 40-79 years, prevalence of NAFLD on admission is high and its metabolic factors are body mass index (BMI), triglycerides (TG), some fatty acids, blood sugar or HbA1c and aspartate aminotransferase / alanine aminotransferase ratio (AST/ALT ratio) as well as reported in ischemic heart disease. Methods: We included acute stroke patients aged 40-79 years who 1) were admitted from August 2016 to July 2019 within 24 hours of onset, 2) underwent abdominal ultrasonography and 3) took blood examination of serum fatty acids on admission. We evaluated prevalence and associated metabolic factors of non-alcoholic fatty liver disease. Results: Among 1672 acute stroke patients, 676 patients met our inclusive criteria. Their median age was 70 years, 267 patients (39.5%) had NAFLD. In NAFLD and non-NAFLD patients, median age was 68 and 71 years (p2 (p Conclusions: In acute stroke patients aged 40-79 years, prevalence of NAFLD on admission was high and metabolic factors of NAFLD were younger Age, higher BMI, higher serum concentrations of Alb, T-CHO, TG and fatty acids, higher HbA1c and lower AST/ALT ratio.

Background: Increasing obesity rates are related to energy intake with carbohydrate and fat ratio. Using Korean National Health and Nutrition Examination Survey 2007-2017 data, we examined the hypothesis that the fat intake and food sources of dietary fats had changed over the last 10 years according to gender and obesity status in adult population ≥19 years. Methods: The food intake of each participant was collected by the 24-hour recall method, and nutrient intake including different fatty acids was calculated. The fatty acid intakes from 7 food groups were determined according to gender and obesity status. Results: Body mass index increased in both genders of the obese group over the decade, but it decreased in the normal-weight group. In men, energy intake was higher in the obese group than in the lean group, but the opposite trend was shown in women. Total fat intake including various fatty acids continuously and sharply increased in both men and women until 2016, then slightly declined only in men. The source of saturated fatty acid (SFA) intake was mainly from the animal food group in men and women regardless of obese status, and SFA and monounsaturated fatty acid from the animal food group gradually increased over time in both genders. N-3 fatty acid intake markedly decreased from fish and crabs and increased from sauces and nuts regardless of genders and the obese status from 2008 to 2017. Polyunsaturated fatty acid and N-6 fatty acid intake increased from bread, cookies, sauces, and nuts regardless of genders and obesity status. Conclusion: Fat intake was higher in obese men, but this was opposite in women. The N-3 fatty acid intake from seafood should increase, and the fat composition in sauce needs to be modulated to increase N-3 fatty acids.

BACKGROUND A deficiency of maternal thyroid hormones (THs) during pregnancy has severe impacts on fetal brain development. Neural stem cells (NSCs) are major targets of THs and provided a powerful model to explore the underlying mechanism of THs during brain development. Although miRNA-125 might be associated with the NSCs differentiation, the relationship between miR-125 and hypothyroidism (HypoT) development remains unclear. MATERIAL AND METHODS In our study, we screened a differentially expressed gene miR-125b-5p from brain between euthyroid (EuT) and HypoT rats. In vitro, we employed anion exchange resin to remove THs to stimulate HypoT. QRT-PCR and Western blot were used to examine the expression of signal transducer and activator of transcription 3 (Stat3). The relationship between miR-125b-5p and Stat3 was detected via a dual-luciferase assay. RESULTS QRT-PCR results showed that the level of miR-125b-5p in HypoT rat brains was significantly suppressed, suggesting some relationship between miR-125b-5p and HypoT. In C17.2, miR-125b-5p promoted cell differentiation into neurons by regulating the expression of tubulin beta chain 3 (TUBB3) and glial fibrillary acid protein (GFAP). QRT-PCR and Western blot results revealed that miR-125b-5p mimic modulated the contents of total Stat3 and p-Stat3. A dual-luciferase assay showed that miR-125b-5p negatively regulated the expression of Stat3 by binding with the first site in 3' UTR of Stat3. CONCLUSIONS These results revealed Stat3 is a new target of miR-125b-5p and revealed the mechanism of miR-125b-5p suppressing HypoT development. These findings provide a new target for HypoT therapy.

Hospitalized patients with heart failure (HF) undergoing bedside glucose monitoring with subcutaneous insulin orders were retrospectively identified over 2 years. Hypoglycaemia was defined as any glucose value

Hypothyroidism is a protective factor against breast cancer but long-term exposure or overdoses of thyroid replacement therapy with thyroxine (T4) may increase breast cancer risk. Objective: to study, in vivo and in vitro, the effects of T4 on the proliferation and apoptosis of mammary tumors of hypo- and euthyroid rats, and the possible mechanisms involved in these effects. Material and Methods: Female Sprague-Dawley rats were treated with a single dose of dimethylbenzathracene (15 mg/rat) at 55 days of age and were divided into three groups: hypothyroidism (HypoT; 0.01% 6-N-propyl-2-thiouracil -PTU- in drinking water, n = 20), hypothyroidism treated with T4 (HypoT + T4; 0.01% PTU in drinking water and 0.25 mg/kg/day T4 via sc; n = 20) and EUT (untreated control, n = 20). At sacrifice, tumor explants from HypoT and EUT rats were obtained and treated either with 10−10 M T4 in DMEM/F12 without phenol red with 1% Charcoalized Fetal Bovine Serum or DMEM/F12 only for 15 min to evaluate intracellular signaling pathways associated with T4, and 24 h to evaluate changes in the expression of hormone receptors and proteins related to apoptosis and proliferation by immunohistochemistry and Western Blot. Results: In vivo, hypothyroidism retards mammary carcinogenesis but its treatment with T4 reverted the protective effects. In vitro, the proliferative and anti-apoptosis mechanisms of T4 were different regarding the thyroid status. In EUT tumors, the main signaling pathway involved was the cross-talk with other receptors, such as ERα, PgR, and HER2. In HypoT tumors, the non-genomic signaling pathway of T4 was the chief mechanism involved since αvβ3 integrin, HER2, β-catenin and, downstream, PI3K/AKT and ERK signaling pathways were activated. Conclusion: T4 can regulate mammary carcinogenesis by mainly activating its non-genomic signaling pathway and by interacting with other hormone or growth factor pathways endorsing that overdoses of thyroid replacement therapy with T4 can increase the risk of breast cancer.

Substance misuse among criminally delinquent youth has typically been described as a concurrent part of their participation in risky and delinquent behavior. Using Khantzian’s self-medication hypot...

Thyroid pathologies have deleterious effects on lactation. Especially hypothyroidism (HypoT) induces premature mammary involution at the end of lactation and decreases milk production and quality in mid lactation. Milk synthesis is controlled by JAK2/STAT5 signaling pathway and prolactin (PRL), which activates the pathway. In this work we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT on PRL signaling pathway on mammary glands from rats on lactation (L) days 2, 7 and 14. HypoT decreased prolactin receptor expression, and expression and activation of Stat5a/b protein. Expression of members of the SOCS-CIS family, inhibitors of the JAK-STAT pathway, decreased in L2 and L7, possibly as a compensatory response of the mammary cells to maintain PRL responsiveness. However, on L14, the level of these inhibitors was normal and the transcription of α-lactoalbumin (lalba), a target gene of the PRL pathway, decreased by half. HypoT altered the transcriptional capacity of the cell and decreased mRNA levels of Prlr and Stat5b on L14. Stat5b gene has functional thyroid hormone response elements in the regulatory regions, that bind thyroid hormone receptor β (TRβ) differentially and in a thyroid hormone dependent manner. The overall decrease in the PRL signaling pathway and consequently in target gene (lalba) mRNA transcription explain the profound negative impact of HypoT on mammary function through lactation. Fil: Campoverde Arbocco, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Persia, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Hapon, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Background: Breast cancer survivors often rate their general health as good even though they experience detriments in functioning and multiple symptoms. The hypothesis of this study is that breast cancer survivors changed their frames of reference for evaluating their own health. Methods: A sample of 308 breast cancer survivors were asked to assess their state of health on a 0-100 scale. In addition, 2 vignettes (fictional persons suffering from various health complaints) were designed. The cancer survivors were asked to assess the health of the characters in these vignettes as well. A sample of the general population (n = 639) served as controls. Results: There were only marginal differences between the cancer survivors (M = 65.8) and the controls (M = 65.5) in how they assessed their own state of health. However, the cancer survivors rated the vignette character with physical problems as being significantly healthier compared to the general population (effect size: d = 0.55). The group differences in the assessment of the vignette character with mental problems was markedly lower (d = 0.12). Conclusions: It is not sufficient to assess the general self-assessed health state of cancer survivors. Anchoring vignettes are a promising tool for use in correcting for response shift effects.

Background: Although β-blockers (BB) could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. Aim: To determine the relationship between type of BB and incidence of hypoglycemia and mortality in hospitalized patients. Methods: We retrospectively identified non-critically ill hospitalized patients who were undergoing bedside glucose monitoring over a 2 year period. Admission BB was categorized as carvedilol (C) or selective BB (SBB). Other nonselective BB were excluded. Hypoglycemia was defined as any glucose < 70 mg/dl within 24 hours of admission (Hypo24) or throughout hospitalization (HypoT) and any glucose Results: There were 1022 patients on C, 886 on SBB, and 10,217 on no BB. After controlling for other variables, the odds of Hypo24 HypoT and Hypo40 were higher for BB recipients, and the odds were greater for SBB vs. carvedilol for HypoT (Table). Findings were not observed in heart failure patients. Hypo24, HypoT, and Hypo40 were all associated with increased mortality in adjusted models among non-BB and C recipients, but not among SBB recipients. Conclusions: BB use is associated with hypoglycemia, except in heart failure. C is associated with lower odds of hypoglycemia compared to SSB. Moreover, hypoglycemia associated mortality was attenuated with C. The findings warrant further study among patients with diabetes. Disclosure C. Long: None. P.F. Binkley: None. K.M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Elsevier, Sanofi-Aventis. Research Support; Self; Eli Lilly and Company, GlaxoSmithKline plc., Novo Nordisk Inc., Sanofi-Aventis, Viacyte. Other Relationship; Self; DKBmed, UpToDate.

Introduction: Previous studies of the relationship between cerebral small vessel disease (CSVD) lesions and carotid artery (CA) calcifications have yielded conflicting results. Hypothesis: We hypothesized that intracranial ICA (ICICA) calcifications are most closely associated with CSVD in comparison to extracranial ICA (ECICA) and common CA (CCA) calcifications. Methods: Acute ischemic stroke and transient ischemic attack patients were recruited into a hospital-based prospective stroke registry. Total CSVD burden score including white matter hyperintensity (WMH), lacunes, microbleeds (MBs) and enlarged perivascular spaces (PVS) was measured according to Staals et al. Fazekas scale was used to rate the periventricular and deep WMH (PVMH and DWMH respectively). ICICA calcifications were measured on plain head CT scan according to Subedi et al. ECICA and CCA calcifications were measured according to Yamada et al on the neck CT angiography. Univariate analyses were used to test the relationship between CSVD lesions and CA calcifications. Binary and ordered logistic regression analyses were performed to adjust for the effect of age, sex, race, history of hypertension, diabetes and current smoking for the variables that showed significance in the univariate analyses. Results: 141 patients (age 64.5±15.3, 49% females, total CSVD score 1.6±1.4, ICICA, ECICA and CCA calcification scores were 7.8±9.9, 10.3±13.4 and 2.1±6.9, respectively). In Univariate analyses, ICICA calcification score showed significant relationships with PVMH, DWMH, lacunes, MBs and total CSVD scores ( P values: Conclusions: ICICA calcifications are most closely linked to PVMW and DWMH. Further studies are required to investigate the pathophysiological mechanisms behind this relationship.

This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human MFCs on a collagen scaffold were stimulated to form fibrocartilage over 6 weeks under normoxic (NRX, 20% O2) conditions with supplemented TGF-β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O2) and then 5 min of dynamic compression (DC) between 30 and 40% strain. Delayed HYP induced an anabolic and anti-catabolic expression profile for hyaline cartilage matrix markers, while DC induced an inflammatory matrix remodeling response along with upregulation of both SOX9 and COL1A1. There were 41 genes regulated by both HYP and DC. Overall, the combined treatment supported a unique gene expression profile favouring the hyaline cartilage aspect of inner meniscus matrix and matrix remodeling.

Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoT+PT) as compared to patients with postsurgical HypoT and healthy controls. Age- and gender-matched patients on treatment for HypoT+PT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoT+PT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoT+PT compared with HypoT. WHO-5 well-being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoT+PT, but not in HypoT. In HypoT+PT, the time spent on the Timed Up & Go test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoT+PT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoT+PT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoT+PT patients are warranted. © 2016 American Society for Bone and Mineral Research.

Using 77 status-imbalanced dyads, we experimentally test the effect of status on identity stability, setting the stage for research on identity change. From an identity theory perspective, we hypothesize that those with higher status will maintain greater identity stability over the course of a task-oriented interaction than their relatively lower status partners. We further test the role of identity-discrepant information. Results indicate that higher status actors are better able to maintain stable identity meanings than those with lower status. However, this relationship dissipates when situational meanings contrast with high-status actors’ self-views. More generally, this indicates that high status positively affects identity stability, yet high-status actors remain vulnerable to situational inputs.

1074 Background: In the Triple Negative Trial we observed no improved response rate (RR) to C over D in aTNBC [Tutt et al, Nat Med 2018], but we did in BRCA1/2 mutated (mut) patients (pts). We hypothesise tumors with other aberrant DNA damage response (DDR) characteristics having higher RR to DNA damage inducing C than D. Methods: We tested the predictive value of DDR process related gene expression signatures (PARPi7, chromosomal instability CIN70, TP53 & DDR Deficiency (DDRD)) on 192 treatment naïve primary tumours (PT) by total RNA-sequencing. Odds ratio (OR) for RR are reported. Paired PT & recurrent (REC) signature scores were compared. Results: Unexpectedly, high DDRD and PARPi7 were associated with higher RR to D than C ( p =0.01 & 0.06). No effect was observed for CIN70 or TP53 signature. To assess whether the unexpected results were due to biological changes 12 PT-REC pairs were available from pts who received chemotherapy (CT) between PT & REC. CIN70 increased from PT to REC, DDRD (non-significantly) & PARPi7 decreased. 4/5 TP53 wildtype classified PT samples classified as mut in REC. The BRCA1/2 & DDRD-treatment interactions only held in pts who received CT before trial entry (table). The PARPi7-treatment interaction only held in CT naïve pts. In CT naïve pts, high CIN70 tumors suggested higher C RR as hypothesized. Restricted to the 149 PAM50 basal-like pts, results were non-significant but similar trends seen. Conclusions: In this trial of aTNBC, DDRD high pts with prior CT had better RR to D than C. A possible explanation for this unexpected result is selective pressure of adjuvant DNA damaging CT and selection for relative taxane sensitivity in those who recur despite a high DDRD score. The hypothesised CIN70 treatment interaction was observed in CT naïve pts. Our results suggest care is required in application of signatures to initial diagnostic material when predicting response to DNA damaging agents at REC particularly in pts with prior CT. [Table: see text]

Introduction and Hypothesis: High troponin levels reflect myocardial damage in patients with heart disease and predict poor prognosis in stroke and cardiomyopathies. In the study, we test the hypothesis that high troponin levels in the setting of chronic renal insufficiency (CRI) significantly predict the risk of first time stroke. Method: The Chronic Renal Insufficiency Cohort Study enrolled a total of 3,477 patients with no previous history of stroke at baseline were used in this study. High troponin level is defined as troponin levels ≥0.03 ug/L. Incident hemorrhagic and ischemic strokes were classified using ICD-9. The associations between baseline troponin levels and incidence of hemorrhagic and ischemic stroke and risk of all-cause mortality were analyzed prospectively using multivariate Cox’s regression analysis technique. Results: With an average (SD) of 7.7 (1.5) years of follow-up, 23 participants developed incident hemorrhagic stroke (HS), and 84 developed incident ischemic stroke (IS). Participants with high troponin had significantly higher IS rate than those with low troponin (9.69% vs. 2.81%, p Conclusion: In CRI patients elevated serum troponin levels were significantly associated with the risk of first time IS and higher all-cause mortality risk. The risk is further amplified significantly in females compared to males indicating sex differences play an important role in first time stroke risk in CRI. These findings represent an unexplored risk of IS.

Thyroid hormones (TH) regulate mammary function. Hypothyroidism (HypoT) has deleterious effects on lactation, litter growth and survival. We analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT in the expression of nuclear receptors, co-regulators and oxytocin receptor (OTR) on lactation (L) days 2, 7 and 14. TH receptors (TRs) were increased on L7 at mRNA and protein levels, except TRα protein, that fell on L14. HypoT decreased TRα2 mRNA on L7 and TRα1 protein on L2, while TRβ1 protein increased on L14. HypoT increased estrogen receptor β (ERβ) mRNA on L7 but decreased its protein levels on L14. Progesterone receptor A (PRA) mRNA decreased from L2 to L14 while PRB increased, and at protein levels PRA levels showed a nadir on L7, while PRB peaked. HypoT decreased PRA mRNA and protein and increased PRB mRNA at L14. Nuclear receptor co-activator (NCOA) 1 and RXRα mRNA showed an opposite pattern to the TRs, while NCOA2 increased at L14; HypoT blocked the variations in NCOA1 and NCOA2. HypoT increased NCOR1 on L2 and decreased OTR at L2 and circulating estradiol and NCOR2 at L14.In controls the most notable changes occurred on L7, suggesting it is a key inflection point in mammary metabolism. The low levels of TRα1, NCOA1 and OTR, and increased NCOR1 produced by HypoT on L2 may hinder the mammary ability to achieve normal milk synthesis and ejection, leading to defective lactation. Later on, altered ER and PR expression may impair further mammary function. Fil: Campo Verde Arbocco, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Sasso, Corina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Nasif, Daniela Lucía. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina Fil: Hapon, María Belén. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Stimulation of angiotensin II type I receptors (AT1R) elicits vasoconstriction (VC) that may be occurring through the activation of a pathogenic vascular pathway such as Rho kinase (ROCK). We hypothesize that reflex cutaneous VC to whole body cooling (mean skin temperature = 30.5°C) in older humans relies in part on AT1R activation, which may explain greater ROCK activity attendant with aging. Two microdialysis (MD) fibers were placed in the forearm skin of 10 young (Y; 24 ± 1 yr) and 10 older (O; 70 ± 2 yr) individuals for infusion of 1) lactated Ringer's solution (switched to fasudil, a ROCK antagonist, after cooling); and 2) AT1R blockade with losartan. Laser Doppler flux (LDF) was measured over each MD site and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/mean arterial pressure) and expressed as percent change from baseline (%ΔCVCBASELINE). In older individuals the VC response to whole body cooling was blunted (Y = −34 ± 2, O = −17 ± 3%ΔCVC) and was further attenuated at the losartan site (Y = −34 ± 3, O = −9 ± 3%ΔCVC; P < 0.05). The VC response to an exogenous 10-μM dose of angiotensin II (Y = −27 ± 3, O = −42 ± 5%ΔCVC) was completely blocked in sites pretreated with losartan or with fasudil. These data suggest that AT1R activation contributes to the reflex VC response in aged but not young skin. Furthermore, the angiotensin II component of the VC response appears to occur primarily through a ROCK-mediated mechanism.

Background Purkinje cells ( PC s) are important in cardiac arrhythmogenesis. Whether small‐conductance calcium‐activated potassium ( SK ) channels are present in PC s remains unclear. We tested the hypotheses that subtype 2 SK ( SK 2) channel proteins and apamin‐sensitive SK currents are abundantly present in PC s. Methods and Results We studied 25 normal rabbit ventricles, including 13 patch‐clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining. Transmembrane action potentials were recorded in current‐clamp mode using the perforated‐patch technique. For PC s, the apamin (100 nmol/L) significantly prolonged action potential duration measured to 80% repolarization by an average of 10.4 ms (95% CI , 0.11–20.72) (n=9, P =0.047). Voltage‐clamp study showed that apamin‐sensitive SK current density was significantly larger in PC s compared with ventricular myocytes at potentials ≥0 mV. Western blotting of SK 2 expression showed that the SK 2 protein expression in the midmyocardium was 58% ( P =0.028) and the epicardium was 50% ( P =0.018) of that in the pseudotendons. Immunostaining of SK 2 protein showed that PCs stained stronger than ventricular myocytes. Confocal microscope study showed SK 2 protein was distributed to the periphery of the PC s. Conclusions SK 2 proteins are more abundantly present in the PC s than in the ventricular myocytes of normal rabbit ventricles. Apamin‐sensitive SK current is important in ventricular repolarization of normal PC s.

To describe the evolution of thyroid dysfunction in a series of patients with cancer treated with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) monoclonal antibody, nivolumab.Cases of thyroid dysfunction after initiation of checkpoint inhibitor treatment were identified from the Division of Endocrinology clinical practice at Mount Sinai Hospital, New York from April 2016 to February 2017. Charts were reviewed to identify patients treated with nivolumab with new onset of thyroid dysfunction.Nine cases of thyroid function in patients who were treated with nivolumab were identified. There were 4 male and 5 female patients, with a mean age of 66 years (range 50-76 years). Seven patients ultimately developed hypothyroidism. Five of the 7 patients developed abnormal thyroid function tests within the first 90 days of starting therapy (range 21-84 days), 3 of whom had transient hyperthyroidism. Transient hyperthyroidism evolved rapidly to hypothyroidism; elevated thyroid-stimulating hormone (TSH) levels were detected within 16 to 32 days of the last documented low TSH. In the 2 patients without a hyperthyroid phase, TSH levels50 were found 18 to 28 days after the last normal TSH value.As the use of immune checkpoint inhibitor therapy increases, the need for prompt diagnosis and treatment of drug-induced thyroid disease will become more important. As illustrated in this case series, in contrast to other causes of auto-immune thyroiditis, hypothyroidism can develop rapidly within 3 months of treatment. Close monitoring is necessary to detect the development of thyroid dysfunction and avoid preventable morbidity.Anti-TPO Abs = anti-thyroglobulin antibodies; CT = computed tomography; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; FDA = U.S. FoodDrug Administration; FDG-PET = fluorodeoxyglucose-positron emission tomography; PD-1 = programmed cell death protein-1; PD-L1 = programmed death-ligand 1; T3 = triiodothyronine; T4 = thyroxine; TG = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone.

ObjectiveIn the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1second (FEV1) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma.MethodsAs part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV1% predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations.ResultsPrevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p < 0.001). After adjusting for covariates, breastfeeding was associated with a 3.58% point increase in FEV1% predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only.ConclusionBreastfeeding was associated with higher FEV1% predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Background— Patients with recovery of left ventricular ejection fraction (LVEF) remain at risk for future deterioration of LVEF. However, there are no tools to risk stratify these patients. We hypothesized that global longitudinal strain (GLS) could predict sustained recovery within this population. Methods and Results— We retrospectively identified 96 patients with a reduced LVEF 50%) on evidence-based medical therapies (baseline echocardiogram). We examined absolute GLS on the baseline echocardiogram in relation to changes in LVEF on a follow-up echocardiogram. Patients with recovered LVEF had a wide range of GLS. The GLS on the baseline study correlated with the LVEF at the time of follow-up ( r =0.33; P 50% on follow-up increased by 24% for each point increase in absolute GLS on the baseline study (odds ratio, 1.24; P =0.001). An abnormal GLS (≤16%) at baseline had a sensitivity of 88%, a specificity of 46%, and an accuracy of 0.67 ( P 5% during follow-up. A normal GLS (>16%) on the baseline study had a sensitivity of 47%, a specificity of 83%, and an accuracy of 0.65 ( P =0.002) for predicting a stable LVEF (−5% to 5%) on follow-up. Conclusions— In patients with a recovered LVEF, an abnormal GLS predicts the likelihood of having a decreased LVEF during follow-up, whereas a normal GLS predicts the likelihood of stable LVEF during recovery.

Carcinoid syndrome is the constellation of symptoms mediated by humoral factors produced by some carcinoid tumors. It consists primarily of vasomotor symptoms, gastrointestinal hypermotility, hypotension, and bronchospasm, due to the production and release of vasoactive substances. Carcinoid heart disease occurs in more than 50% of patients with carcinoid syndrome; in some cases, it represents the initial manifestation of the disease. We report the case of a 75-year-old woman with a metastatic neuroendocrine tumor admitted to the emergency room for fatigue and heart failure. Transthoracic echocardiography showed severe tricuspid and pulmonic regurgitation suggesting carcinoid heart disease. A hypervascular retroperitoneal mass was found on abdominal computed tomography, which seemed to arise from the mesenteric artery, anteriorly to the abdominal aorta. Unfortunately, our patient was neither a candidate for mass resection nor for cardiac surgery due to advanced metastatic disease and poor clinical condition. Additionally, we performed a systematic literature review of carcinoid heart disease focusing on typical echocardiographic findings.