Clinical Protocol for Selecting Intracardiac or Transesophageal Echocardiography-Guided Left Atrial Appendage Occlusion.

Intracardiac echocardiography (ICE) has emerged as an alternative to transesophageal echo (TEE) to guide left atrial appendage occlusion (LAAO). We established a protocol to select patients appropriate for ICE guidance. Patients who underwent LAAO with the Watchman or Watchman FLX device (Boston Scientific, Marlborough, Massachusetts) from January 2018 to March 2022 at a large United States center were included. The novel protocol prospectively selected TEE or ICE guidance beginning in January 2020; previous LAAO procedures were retrospectively included. ICE was selected for patients with uninterrupted anticoagulation and appropriate LAA anatomy, renal function, and moderate sedation tolerance. In-hospital outcomes with successful implantation without conversion to TEE guidance, no peridevice leak, and no procedural complications were compared. Composite 1-year outcome included freedom from peridevice leak, device-related thrombus, stroke, and all-cause mortality. A total of 234 patients were included; the mean age was 76.1 ± 8.3 years old, and 42.3% were female. ICE guidance was used for 63 procedures; TEE guidance was used for 171 procedures. For the composite outcome, ICE-guided LAAO was superior to TEE-guided LAAO (risk difference 0.102, 96.8% vs 86.5%, 95% confidence interval 0.003 to 0.203, p = 0.029). In comparison to the TEE-guided group, ICE-guided procedures were shorter (89.1 ± 26.3 vs 99.8 ± 30.0 min, p = 0.0087) with less general anesthesia (26.6% vs 98.8%, p <0.0001). One-year composite adverse outcomes did not differ significantly (80.7% vs 88.9%, p = 0.17). In conclusion, the protocol to select appropriate patients for ICE versus TEE guidance for LAAO is safe and effective. Larger studies are indicated to validate this approach to improve outcomes, shorten procedures, and avoid general anesthesia.

Prevalence and Impact of Poorly Controlled Modifiable Risk Factors Among Patients Who Underwent Atrial Fibrillation Ablation.

Managing atrial fibrillation (AF) risk factors (RFs) improves ablation outcomes in obese patients. However, real-world data, including nonobese patients, are limited. This study examined the modifiable RFs of consecutive patients who underwent AF ablation at a tertiary care hospital from 2012 to 2019. The prespecified RFs included body mass index (BMI) ≥30 kg/m2, >5% fluctuation in BMI, obstructive sleep apnea with continuous positive airway pressure noncompliance, uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, tobacco use, alcohol use higher than the standard recommendation, and a diagnosis-to-ablation time (DAT) >1.5 years. The primary outcome was a composite of arrhythmia recurrence, cardiovascular admissions, and cardiovascular death. In this study, a high prevalence of preablation modifiable RFs was observed. More than 50% of the 724 study patients had uncontrolled hyperlipidemia, a BMI ≥30 mg/m2, a fluctuating BMI >5%, or a delayed DAT. During a median follow-up of 2.6 (interquartile range 1.4 to 4.6) years, 467 patients (64.5%) met the primary outcome. Independent RFs were a fluctuation in BMI >5% (hazard ratio [HR] 1.31, p = 0.008), diabetes with A1c ≥6.5% (HR 1.50, p = 0.014), and uncontrolled hyperlipidemia (HR 1.30, p = 0.005). A total of 264 patients (36.46%) had at least 2 of these predictive RFs, which was associated with a higher incidence of the primary outcome. Delayed DAT over 1.5 years did not alter the ablation outcome. In conclusion, substantial portions of patients who underwent AF ablation have potentially modifiable RFs that were not well controlled. Fluctuating BMI, diabetes with hemoglobin A1c ≥6.5%, and uncontrolled hyperlipidemia portend an increased risk of recurrent arrhythmia, cardiovascular hospitalizations, and mortality after ablation.

Changes in the excitability of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields.

Exposures to radiofrequency electromagnetic fields (RF-EMFs, 100 kHz to 6 GHz) have been associated with both positive and negative effects on cognitive behavior. To elucidate the mechanism of RF-EMF interaction, a few studies have examined its impact on neuronal activity and synaptic plasticity. However, there is still a need for additional basic research that further our understanding of the underlying mechanisms of RF-EMFs on the neuronal system. The present study investigated changes in neuronal activity and synaptic transmission following a 60-min exposure to 3.0 GHz RF-EMF at a low dose (specific absorption rate (SAR) < 1 W/kg). We showed that RF-EMF exposure decreased the amplitude of action potential (AP), depolarized neuronal resting membrane potential (MP), and increased neuronal excitability and synaptic transmission in cultured primary hippocampal neurons (PHNs). The results show that RF-EMF exposure can alter neuronal activity and highlight that more investigations should be performed to fully explore the RF-EMF effects and mechanisms.

How risky are heroin markets? A multi-site study of self-reported risk perceptions among police detainees in Australia.

BACKGROUND: There has long been an international interest in the eradication of drug markets-particularly heroin markets-given their documented connection to the deterioration of local community and social amenity. Recent interest in focused drug law enforcement strategies has reinvigorated debate about the potential for deterrence; however, there exists no large-scale effort to document the risk perceptions of those who transact in heroin markets. METHODS: We use data from 2,257 police detainees interviewed as part of the Australian Institute of Criminology's (AIC) Drug Use Monitoring in Australia (DUMA) program. We employ a multilevel generalised ordinal logistic regression model to explore the geographical and temporal heterogeneity of risk, controlling for individual demographic covariates. RESULTS: With one exception, we find a surprising degree of homogeneity at the high end of the risk perception scale, with between 30 and 35 percent of respondents rating their local heroin market as very risky. At the low end, there was greater geographical and temporal variability with between 15 and 30 percent of respondents rating their market as not at all risky. One location stands out as anomalous, being perceived as considerably more risky. Of the demographic and drug-use covariates, only age and gender were statistically significant. Neither the length nor frequency of association with the heroin market predicted lower levels of risk perception. CONCLUSION: A little over half of all heroin market participants consider transacting in their local market to be somewhat or very risky-the others consider it not at all or only a little risky. With few exceptions, this broad pattern appears consistent over time and between geographical locations, although an individual's personal perception is not tied to their degree of exposure to the heroin market. The policy implications of these findings are discussed.

Altered gait mechanics are associated with severity of chondropathy after hip arthroscopy for femoroacetabular impingement syndrome.

BACKGROUND: Suboptimal patient-reported function and movement impairments often persist after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Individuals with FAIS with preoperative cartilage pathology (ie. chondropathy) demonstrate distinct movement patterns and have worse post-operative outcomes. It is unknown whether the presence of chondropathy after surgery negatively affects movement and function. RESEARCH QUESTION: Do sagittal plane gait mechanics differ based on chondropathy severity following arthroscopy for FAIS? METHODS: A cross-sectional walking gait analysis was performed for 25 participants post-arthroscopy (2.48 ±â€¯1.38y) and 12 healthy controls (HCs). Peak total support moment (TSM) and relative contributions of the hip, knee, and ankle were calculated during loading response. The Hip Osteoarthritis MRI Scoring System was used to categorize the FAIS group into no-mild or moderate-severe chondropathy groups based on 3 T magnetic resonance imaging of their surgical hip. The interactions of group by limb were evaluated for kinetic variables, covaried by gait speed. RESULTS: Groups did not differ based on age, BMI and sex distribution (P ≥ 0.14). 13 participants with FAIS presented with moderate-severe chondropathy and 12 presented with no-mild chondropathy. Participants with moderate-severe chondropathy walked significantly slower than both other groups (P = 0.006) and demonstrated lower peak TSM than those with no-mild chondropathy (P = 0.002). Participants with no-mild chondropathy demonstrated lower hip (61.5 %) and greater ankle (17.7 %) contributions to the TSM on the involved limb compared to the moderate-severe group (hip:73.4 %, P = 0.07; ankle:10.5 %, P = 0.007). SIGNIFICANCE: Slower gait speed alone did not explain the lower TSM strategy in participants with moderate-severe chondropathy. Interestingly, the joint contribution strategy of this group was not different than HCs. Participants with no-mild chondropathy demonstrated a TSM strategy that shifted the demand away from their hip and toward their ankle. Given the small sample size, and large variability in joint strategies, future work needs to examine whether these alterations in gait strategy, with or without advanced chondropathy, impact patient function.

Fracture Healing in Two Adult Patients With Hypophosphatasia After Asfotase Alfa Therapy.

Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing in adult HPP patients. We present the course of fracture healing in two adults with HPP on enzyme replacement. Case 1 is a 41-year-old female with infantile-onset HPP who was wheelchair-bound due to a nonhealing tibial fragility fracture sustained 3 years before and also had nonhealing femoral pseudofracture sustained 17 years before starting asfotase alfa therapy in December 2015. One month after medication initiation, she underwent elective osteotomy of tibia and fibula with intramedullary nail fixation. After 3 months of enzyme replacement, she was full weight-bearing and radiographs demonstrated callus formation at osteotomy sites, and at 11 months of therapy, radiographs showed union of the osteotomies. By 11 months of asfotase alfa therapy, there was near resolution of the femoral pseudofracture without interval surgery at this site. Case 2 is a 61-year-old male who showed nonunion of a fragility fracture of the right femur 8 years prior, intramedullary nail fixation 6 years prior, and stress fracture of the left femoral diaphysis sustained 1 year before starting asfotase alfa in October 2015. A trial of teriparatide was unsuccessful in healing of these fractures. On asfotase alfa, radiographs revealed interval healing of the left femur fracture after 12 months and complete healing of the right femur fracture and near resolution of the left femur fracture after 16 months of medical therapy. These two adult patients with HPP showed significant clinical and radiographic improvements in a total of four recalcitrant fractures on enzyme replacement therapy with asfotase alfa. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis.

BACKGROUND: Painful events are the leading cause of hospitalizations for patients with sickle cell disease. Individualized pain plans targeting patient-specific maximum opioid dosing may shorten hospitalization length and are recommended by national guidelines. Prior to implementing individualized sickle cell pain plans, we tested the hypothesis that a shorter time to achieve a maximum opioid dose would improve hospitalization outcomes. PROCEDURE: Two-year IRB-approved, retrospective study of pediatric patients admitted for vaso-occlusive crisis (VOC). We recorded the emergency department admission time, order entry time for the maximum opioid dose during the hospitalization, and time of discharge orders.  We categorized patients as infrequent if they required <3 admissions for VOC over two years and patients as frequent if they required ≥3 admissions for VOC over two years. To account for multiple admissions, generalized linear modeling was performed. RESULTS: We identified 236 admissions for acute pain observed in 108 patients. Achieving an earlier maximum opioid dose was significantly associated with shorter length of hospitalization for frequent and infrequent pain patients (both P ≤ 0.0001). As total hospitalization length can be impacted by the time a maximum opioid order was placed, we also analyzed hospitalization length after the maximum opioid order was placed. Frequent pain patients who achieved earlier analgesia had a significantly shorter hospitalization from the time the maximum opioid order was placed (P = 0.03) while no association was found for infrequent pain patients (P = 0.84). CONCLUSIONS: Early achievement of maximum analgesia improved hospitalization outcomes and warrant further investigation in prospective studies of individualized pain plans.

Management of severe chronic pain with methadone in pediatric patients with sickle cell disease.

Vasocclusive pain crises are common among pediatric patients with sickle cell disease (SCD). Some patients with repeated pain crises develop chronic pain. We performed a retrospective cohort study of pediatric patients with SCD with chronic pain treated with methadone. We identified a significant reduction in pain hospitalizations following methadone treatment (0.35 ± 0.19 vs. 0.19 ± 0.17 hospitalizations/month, P = 0.016). In addition, we did not observe overt organ toxicity nor symptoms of opioid withdrawal during methadone wean. We suggest that methadone is safe and has some clinical benefit, which should be proven in prospective randomized trials for pediatric patients with SCD and chronic pain.

Development of dihydrochalcone-functionalized gold nanoparticles for augmented antineoplastic activity.

BACKGROUND: Phloridzin, an antidiabetic and antineoplastic agent usually found in fruit trees, is a dihydrochalcone constituent that has a clinical/pharmaceutical significance as a sodium-glucose linked transport 2 (SGLT2) inhibitor. While the aglycone metabolite of phloridzin, phloretin, displays a reduced capacity of SGLT2 inhibition, this nutraceutical displays enhanced antineoplastic activity in comparison to phloridzin. PURPOSE: The objective of this study was to develop gold nanoparticle (AuNP) mediated delivery of phloridzin and phloretin and explore their anticancer mechanism through conjugation of the dihydrochalcones and the AuNP cores. METHODS: Phloridzin and phloretin conjugated AuNPs (Phl-AuNP and Pht-AuNP) were synthesized in single-step, rapid, biofriendly processes. The synthesized AuNPs morphology was characterized via transmission electron microscopy and ultraviolet-visible spectroscopy. The presence of phloridzin or phloretin was confirmed using scanning electron microscopy-energy dispersive x-ray spectroscopy. The percentage of organic component (phloridzin/phloretin) onto AuNPs surface was characterized using thermogravimetric analysis. Assessment of the antineoplastic potency of the dihydrochalcones conjugated AuNPs against cancerous cell lines (HeLa) was accomplished through monitoring via flow cytometry. RESULTS: The functionalized AuNPs were synthesized via a single-step method that relied only upon the redox potential of the conjugate itself and required no toxic chemicals. The synthesized Phl-AuNPs were found to be in the size range of 15±5 nm, whereas the Pht-AuNP were found to be 8±3 nm, placing both conjugated AuNPs well within the size range necessary for successful pharmaceutical applications. These assays demonstrate a significant increase in the cancerous cell toxicities as a result of the conjugation of the drugs to AuNPs, as indicated by the 17.45-fold increase in the efficacy of Pht-AuNPs over pure phloretin, and the 4.49-fold increase in efficacy of Phl-AuNP over pure phloridzin. CONCLUSION: We report a simple, biofriendly process using the reducing and capping potential of the dihydrochalcones, phloridzin and phloretin, to synthesize stable AuNPs that have promising futures as potential antineoplastic agents.

Comparison of the prognostic value of non-ischaemic fractional flow reserve using intracoronary versus intravenous adenosine.

AIMS: Intracoronary adenosine (ICA) yields similar fractional flow reserve (FFR) results to the "gold standard" of intravenous adenosine (IVA). Whether they have similar prognostic significance is unknown. We therefore sought to study the prognostic value of the route of adenosine administration for the measurement of FFR in deferred coronary lesions in a large, real-world cohort. METHODS AND RESULTS: Five hundred and seventy-six patients with 787 lesions in whom PCI was deferred based on FFR >0.75 were studied. The primary outcome was the first major adverse cardiovascular event (MACE; defined as death, myocardial infarction [MI], or target vessel revascularisation [TVR]), and the secondary outcome was a composite of MI and target vessel failure (TVF). FFR was measured with ICA in 426 lesions and IVA in 361 lesions. Median follow-up duration was 3.2 years (interquartile range: 1.7- 4.6). Propensity-matched cohorts of ICA and IVA were well matched for baseline clinical, angiographic and haemodynamic characteristics. In the propensity-matched cohort, MACE occurred in 23.5% of the ICA group and in 22.3% of the IVA group (p=0.29). On multivariate analysis, acute coronary syndrome, FFR and prior MI/revascularisation were independent predictors of MACE and MI/TVF. The route of adenosine administration was not predictive of MACE or MI/TVF. CONCLUSIONS: ICA and IVA yield similar FFR values and show comparable long-term prognostic utility in a deferred population. These findings provide confirmation that non-ischaemic FFR using a simpler ICA protocol provides prognostic data similar to the gold standard IVA.

Medial Oblique Meniscomeniscal Ligament of Knee.

An aberrant meniscus attachment was found in the setting of an anterior cruciate ligament injury. An anomalous cordlike attachment ran from the anterior horn of the medial meniscus to the posterior horn of the lateral meniscus through the intercondylar notch. Surgeons should be aware of the anatomical variability in the knee in order to provide the best care for their patients.

Clinical Decision-Making for the Hemodynamic "Gray Zone" (FFR 0.75-0.80) and Long-Term Outcomes.

BACKGROUND: Fractional flow reserve (FFR) value between 0.75 and 0.80 is considered the "gray zone" and outcomes data relative to treatment strategy (revascularization vs medical therapy alone [deferral]) are limited for this group. METHODS AND RESULTS: A total of 238 patients (64.3 ± 8.6 years; 97% male; 45% diabetic) with gray-zone FFR were followed for the primary endpoint of major adverse cardiovascular event (MACE), defined as a composite of death, myocardial infarction (MI), and target-vessel revascularization. Mean follow-up duration was 30 ± 17 months. Deferred patients (n = 48 [20%]) had a higher prevalence of smoking and chronic kidney disease compared with the percutaneous coronary intervention (PCI) group (n = 190 [80%]; P<.05). Patients who underwent PCI had significantly lower MACE compared with the deferred patients (16% vs 40%; log rank P<.01). While there was a trend toward a decrease in all-cause mortality (8% vs 19%; log rank P=.06), the composite of death or MI was significantly lower in the PCI group (9% vs 27%; P<.01). On multivariate Cox proportional hazards regression analysis, PCI was associated with lower MACE (hazard ratio, 0.5; 95% confidence interval, 0.27-0.95; P=.03). CONCLUSION: Revascularization for patients with gray-zone FFR was associated with a significantly reduced risk of MACE compared with medical therapy alone.

Massive localized lymphedema: a clinicopathologic study of 46 patients with an enrichment for multiplicity.

Massive localized lymphedema is a monstrous tumefactive pseudosarcoma seen in middle-aged morbidly obese adults. Since its initial description in 1998, the etiology remains unknown, although associations with trauma, surgeries, and hypothyroidism have been reported. Herein, we report the largest study of massive localized lymphedema and expand upon its clinicopathologic features. Fifty-four cases from 46 patients were retrospectively identified from the institutional archives of The Ohio State University Wexner Medical Center between 2002 and 2015. Forty-six patients (21 males and 25 females, mean age 50 years) presented with large masses developing over a 5-60-month period. The majority of patients were Caucasian (n=39). All patients were obese with a mean weight of 384.7 lb and a mean body mass index of 59.6 kg/m(2). Thirty-six patients had a history of atherosclerotic cardiovascular disease and diabetes mellitus type 2 was present in 22 patients. Eight patients had multifocal massive localized lymphedema. The sites included thigh (n=33), abdomen (n=17), suprapubic region (n=1), mons pubis (n=6), scrotum (n=2), perianal region (n=1), and right flank (n=1). Mostly, the clinical impression was benign processes, including pannus or lymphedema pseudotumor. Grossly, the mean weight was 8237 g and the mean size was 53.2 cm. Histologically, eight cases showed a unique pattern of dystrophic calcifications mimicking hyperchromatic, atypical nuclei that might lead to misdiagnosis of liposarcoma, four cases showed focal metaplastic ossification, and three cases showed multinucleated cells in addition to prototypic features of massive localized lymphedema. We report that this is the largest series of massive localized lymphedema. This is a lesion mostly seen in morbidly obese patients and the thigh is the most common site of involvement. We note a marked racial predilection for Caucasians and a tendency towards multiplicity. We suggest that obesity itself and the related metabolic syndrome have an important role in its pathogenesis.

Nanosecond pulsed electric field thresholds for nanopore formation in neural cells.

The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca(2+)), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca(2+) overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using Annexin V and FM1-43, to detect changes in membrane asymmetry, and through Ca(2+) influx using Calcium Green. The ED50 for a single 600 ns pulse, necessary to cause uptake of extracellular Ca(2+), was 1.76 kV/cm for NG108 and 0.84 kV/cm for PHN. At 16.2 kV/cm, the ED50 for pulse width was 95 ns for both cell lines. Cadmium, a nonspecific Ca(2+) channel blocker, failed to prevent Ca(2+) uptake suggesting that observed influx is likely due to nanoporation. These data demonstrate that moderate amplitude single nsPEF exposures result in rapid Ca(2+) influx that may be capable of controllably modulating neurological function.

Association of echocardiographic abnormalities with mortality in men with non-dialysis-dependent chronic kidney disease.

BACKGROUND: The interrelationship of left ventricular hypertrophy (LVH) with ejection fraction (EF) and their impact on mortality in non-dialysis-dependent chronic kidney disease (NDD-CKD) is unclear. METHODS: We examined the associations of EF and LVH with all-cause mortality in a historic cohort of 650 male US veterans with moderate-to-advanced NDD-CKD. EF and LVH were examined both separately and after categorizing patients according to their concomitant EF and presence/absence of LVH. Associations with mortality were examined in Cox models with adjustments for demographics, blood pressure, comorbidities, smoking status, medication use and biochemical characteristics. RESULTS: EF <30 and 30-50% were associated with higher all-cause mortality compared to EF >50% even after multivariable adjustments [multivariable adjusted hazard ratio, 95% confidence interval (CI): 2.83 (1.86-4.30) and 1.38 (1.06-1.78), P < 0.001 for linear trend]. LVH in itself was not associated with mortality [multivariable adjusted hazard ratio, 95% CI: 0.83 (0.66-1.05), P = 0.12], but the presence of LVH combined with an EF <50% was associated with the highest mortality [multivariable adjusted hazard ratios, 95% CI in patients with EF >50% + LVH, EF ≤ 50%-LVH and EF ≤ 50% + LVH, compared to EF >50%-LVH: 0.84 (0.63-1.13), 1.36 (1.00-1.83) and 1.62 (1.07-2.46)]. CONCLUSIONS: Low EF is associated with higher mortality in patients with NDD-CKD. In the presence of a low EF, LVH is also associated with higher mortality. Clinical trials are needed to determine if interventions targeting patients with low EF and LVH can lower mortality in NDD-CKD.

Initial experience of sequential surgical epicardial-catheter endocardial ablation for persistent and long-standing persistent atrial fibrillation with long-term follow-up.

BACKGROUND: Patients with long-standing persistent (LSP) atrial fibrillation (AF) who have previously undergone catheter ablation represent a challenging patient population. Repeat catheter ablation in these patients is arduous and associated with a high failure rate, whereas surgical ablation can be complicated by multiple flutters. We sought to determine if minimally-invasive surgical ablation, followed by catheter ablation of all inducible flutters, would improve success rates over repeat catheter ablation alone. METHODS: Fifteen patients (Sequential) with persistent or LSP AF who failed at least one catheter ablation and one anti-arrhythmic drug (AAD) underwent surgical ablation, followed by planned endocardial evaluation and catheter mapping with ablation during the same hospitalization. Sequential patients were matched to 30 patients who had previously failed at least one catheter ablation and underwent a repeat catheter ablation (catheter-alone). The primary end point was event-free survival of any documented AF recurrence or AAD use. RESULTS: All patients underwent uncomplicated surgical ablation and electrophysiology procedure. Five Sequential patients had seven inducible flutters that were mapped and ablated. After a mean follow-up of 20.7±4.5 months, 13/15 (86.7%) Sequential patients, but only 16/30 (53.3%) catheter-alone patients, were free of any atrial arrhythmia and off of AAD (p=0.04). On AAD, 14/15 (93.3%) Sequential patients were free of any atrial arrhythmia recurrence, compared to 17/30 (56.7%) catheter-alone patients (p=0.01). CONCLUSIONS: For patients with atrial fibrillation who have failed catheter ablation, Sequential minimally invasive epicardial surgical ablation, followed by endocardial catheter-based ablation, has a higher early success rate than repeat catheter ablation alone.

In vitro investigation of the biological effects associated with human dermal fibroblasts exposed to 2.52 THz radiation.

BACKGROUND: Terahertz (THz) radiation sources are increasingly being used in military, defense, and medical applications. However, the biological effects associated with this type of radiation are not well characterized. In this study, we evaluated the cellular and molecular response of human dermal fibroblasts exposed to THz radiation. METHODS: In vitro exposures were performed in a temperature-controlled chamber using a molecular gas THz laser (2.52 THz, 84.8 mW cm(-2), durations: 5, 10, 20, 40, or 80 minutes). Both computational and empirical dosimetric techniques were conducted using finite-difference time-domain (FDTD) modeling approaches, infrared cameras, and thermocouples. Cellular viability was assessed using conventional MTT assays. In addition, the transcriptional activation of protein and DNA sensing genes were evaluated using qPCR. Comparable analyses were also conducted for hyperthermic and genotoxic positive controls. RESULTS: We found that cellular temperatures increased by 3°C during all THz exposures. We also found that for each exposure duration tested, the THz and hyperthermic exposure groups exhibited equivalent levels of cell survival (≥90%) and heat shock protein expression (∼3.5-fold increases). In addition, the expression of DNA sensing and repair genes was unchanged in both groups; however, appreciable increases were observed in the genotoxic controls. CONCLUSIONS: Human dermal fibroblasts exhibit comparable cellular and molecular effects when exposed to THz radiation and hyperthermic stress. These findings suggest that radiation at 2.52 THz generates primarily thermal effects in mammalian cells. Therefore, we conclude that THz-induced bioeffects may be accurately predicted with conventional thermal damage models.

Age-related reduction in estrogen receptor-mediated mechanisms of vascular relaxation in female spontaneously hypertensive rats.

Hypertension increases with aging, and changes in vascular estrogen receptors (ERs) may play a role in age-related hypertension in women. We tested whether age-related increases in blood pressure in female spontaneously hypertensive rats (SHRs) are associated with reduction in amount and/or vascular relaxation effects of estrogen and ER. Arterial pressure and plasma estradiol were measured in adult (12 weeks) and aging (16 months) female SHRs, and thoracic aorta was isolated for measurement of active stress, 45Ca2+ influx, and ERs. Arterial pressure was greater and plasma estradiol was less in aging females than in adult females. In aorta of adult females, Western blots revealed alpha- and beta-ERs that were slightly reduced in aging rats. In endothelium-intact vascular strips, phenylephrine (Phe; 10(-5) mol/L) caused greater active stress in aging rats (9.3+/-0.2) than in adult rats (6.2+/-0.3x10(4) N/m2). 17beta-estradiol (E2) caused relaxation of Phe contraction and stimulation of vascular nitrite/nitrate production, which was reduced in aging rats. In endothelium-denuded strips, E2 still caused relaxation of Phe contraction, which was smaller in aging rats than adult rats. KCl (51 mmol/L), which stimulates Ca2+ influx, produced greater active stress in aging rats (9.1+/-0.3) than in adult rats (5.9+/-0.2x10(4) N/m2). E2 caused relaxation of KCl contraction and inhibition of Phe- and KCl-induced 45Ca2+ influx, which were reduced in aging rats. Thus, aging in female SHR is associated with reduction in ER-mediated NO production from endothelial cells and decrease in inhibitory effects of estrogen on Ca2+ entry mechanisms of smooth muscle contraction. The age-related decrease in ER-mediated vascular relaxation may explain the increased vascular contraction and arterial pressure associated with aging in females.