Παρασκευή, 11 Νοεμβρίου 2016

Unusual presentation of local anesthetic toxicity

The local anesthetic systemic toxicity can be due to increased blood lignocaine levels or due to increased sensitivity to lignocaine. Several cases of lignocaine-induced central nervous system toxicity have been noted, but none have reported only loss of consciousness without any seizure-like activity. Intravenous lipid emulsion administration for the treatment of local anesthetic systemic toxicity is an emerging topic of discussion, and there are case reports where they had successfully been used.

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Veterans Day message from Acadian Ambulance CEO

Acadian Ambulance CEO Richard Zuschlag thanked veterans for their service.

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Go and no-go P3 with rare and frequent stimuli in oddball tasks: A study comparing key-pressing with counting

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Publication date: Available online 11 November 2016
Source:International Journal of Psychophysiology
Author(s): Rolf Verleger, Niels Grauhan, Kamila Śmigasiewicz
The P3 component of event-related potentials (ERPs) is large at posterior scalp sites with rare go stimuli (go-P3) and at anterior sites with rare no-go stimuli (no-go P3). Most hypotheses on P3, including our S-R link reactivation notion, imply that these characteristics are independent of specific response modes. This assumption was here investigated by comparing ERPs between key-pressing and covert counting responses in oddball tasks that required responses to either frequent or rare stimuli. Replicating previous results, topographic differences between parietal rare go-P3 and fronto-central rare no-go P3 were much reduced with counting compared to key-press responses. Besides, while go-P3 was generally more positive than no-go P3 in the key-press tasks (except for fronto-central no-go P3 with rare stimuli) the reverse was true in the counting tasks. Thus, the characteristic posterior and fronto-central go and no-go topographies appear to be specific to hand movements. Moreover, P3s evoked in counting tasks might not simply be P3 proper, uncontaminated by movement-related potentials, but rather the go/no-go logic might differ between counting and key-pressing, with the oddball effects being affected by specific processes implemented for these particular response modes.



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Measuring radon-222 in soil gas with high spatial and temporal resolution

Publication date: Available online 11 November 2016
Source:Journal of Environmental Radioactivity
Author(s): Darren Huxtable, David Read, George Shaw
In order to exploit 222Rn as a naturally-occurring tracer in soils we need to sample and measure radon isotopes in soil gas with high spatial and temporal resolution, without disturbing in situ activity concentrations and fluxes. Minimisation of sample volume is key to improving the resolution with which soil gas can be sampled; an analytical method is then needed which can measure radon with appropriate detection limits and precision for soil gas tracer studies. We have designed a soil gas probe with minimal internal dead volume to allow us to sample soil gas volumes of 45 cm3. Radon-222 is extracted from these samples into a mineral oil-based scintillation cocktail before counting on a conventional liquid scintillation counter. A detection limit of 320 Bq m−3 (in soil gas) is achievable with a 1 h count. This could be further reduced but, in practice, is sufficient for our purpose since 222Rn in soil gas typically ranges from 2000–50,000 Bq m−3. The method is simple and provides several advantages over commonly used field-portable instruments, including smaller sample volumes, speed of deployment and reliability under field conditions. The major limitation is the need to count samples in a liquid scintillation counter within 2–3 days of collection, due to the short (3.824 day) radioactive half-life of 222Rn. The method is not applicable to the very short-lived (55 s half-life) 220Rn.

Graphical abstract

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Tracing the source of sedimentary organic carbon in the Loess Plateau of China: An integrated elemental ratio, stable carbon signatures, and radioactive isotopes approach

Publication date: Available online 11 November 2016
Source:Journal of Environmental Radioactivity
Author(s): Chun Liu, Yuting Dong, Zhongwu Li, Xiaofeng Chang, Xiaodong Nie, Lin Liu, Haibing Xiao, Hassan Bashir
Soil erosion, which will induce the redistribution of soil and associated soil organic carbon (SOC) on the Earth's surface, is of critically importance for biogeochemical cycling of essential elements and terrestrial carbon sequestration. Despite the importance of soil erosion, surprisingly few studies have evaluated the sources of eroded carbon (C). This study used natural abundance levels of the stable isotope signature (13C) and radioactive isotopes (137Cs and 210Pbex), along with elements ratio (C/N) based on a two end member mixing model to qualitatively and quantitatively identify the sources of sedimentary OC retained by check dam in the Qiaozigou small watershed in the Loess Plateau, China. Sediment profiles (0–200 cm) captured at natural depositional area of the basin was compared to possible source materials, which included: superficial Loess mineral soils (0–20 cm) from three land use types [i.e., grassland (Medicago sativa), forestland (Robinia pseudoacacia.), shrubland (Prunus sibirica), and gully land (Loess parent material.)]. The results demonstrated that SOC in sediments showed significantly negative correlation with pH (P < 0.01), and positive correlation with soil water content (SWC) (P < 0.05). The sedimentary OC was not derived from grasslands or gullies. Forestland and shrubland were two main sources of eroded organic carbon within the surface sediment (0–60 cm deep), except for that in the 20–40 cm soil layer. Radionuclides analyses also implied that the surface sediments retained by check-dams mainly originated from soils of forestland and shrubland. Results of the two end-member mixing model demonstrated that more than 50% SOC (mean probability estimate (MPE) 50.13% via 13C and 60.53% via C/N) in surface sediment (0–20 cm deep) derived from forestland, whereas subsurface sedimentary SOC (20–200 cm) mainly resulted from shrubland (MPE > 50%). Although uncertainties on the sources of SOC in deep soils exist, the soil organic δ13C and C/N is still an effective indicator for sources of sedimentary organic carbon in the deposition zone in the short term (<10 years).

Graphical abstract

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Radioprotective effect of Zamzam (alkaline) water: A cytogenetic study

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Publication date: Available online 10 November 2016
Source:Journal of Environmental Radioactivity
Author(s): Fatemeh Keramati Yazdi, Ali Shabestani Monfared, Hamed Tashakkorian, Aziz Mahmoudzadeh, Sajad Borzoueisileh
BackgroundRadioprotectors are useful compounds to reduce radiation toxicity of normal cells. Many natural radioprotectors have antioxidant power and display fewer toxicity and side effects than the chemical ones. Alkaline waters such as Zamzam have antioxidant power potentially. This study aimed to investigate the radioprotective effect of Zamzam water in mice bone marrow exposed to gamma radiation by micronuclei test.MethodFive study groups including control group which was fed by ordinary water, the second group was fed by Zamzam water, and radiation groups were received 2Gy gamma with ordinary and Zamzam water for 10 days and another for 20 days. The frequency of micronuclei and polychromatic erythrocytes to normochromatic erythrocytes ratio were calculated by micronuclei test.ResultIn the absence of radiation, no significant difference was found between Zamzam group and control in the number of micronuclei in normochromatic erythrocytes, micronuclei in polychromatic erythrocytes, and the polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte ratio. But all of these indices were significantly different between irradiated and non-irradiated groups. The frequency of micronuclei in polychromatic erythrocytes was not significantly different between 10 and 20 days Zamzam irradiated groups, but the reduction in micronuclei in normochromatic erythrocytes and an increase in the polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte ratio compared to ordinary water were seen in 20 days Zamzam group. Dose reduction factor was 1.36 and 2 for Zamzam water groups of 10 days and 20 days, respectively.ConclusionThe results demonstrated that Zamzam alkaline water could reduce clastogenic and cytotoxic effects of gamma irradiation.



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Improving transfer functions to describe radiocesium wash-off fluxes for the Niida River by a Bayesian approach

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Publication date: Available online 11 November 2016
Source:Journal of Environmental Radioactivity
Author(s): M. Delmas, L. Garcia-Sanchez, V. Nicoulaud-Gouin, Y. Onda
This paper proposed methodological refinements of the generic transfer function approach to reconstruct radiocesium wash-off fluxes from contaminated catchments, by the integration of hydrological descriptors (passed volume of water, flow rate fluctuations and antecedent flow conditions). The approach was applied to the Niida River (Fukushima prefecture, Japan) for the period 03/2011-03/2015, for which daily flow rate (m3/s) and infrequent total radiocesium concentration (Bq/L) values were available from literature.Three models were defined, generic TF (Φ0), flow-corrected time variant (Φ1) and antecedent-flow corrected variant (Φ2). Calibration of these models' parameters was performed with a Bayesian approach because it is particularly adapted to limited datasets and censored information, and it provides parameters distributions.The model selection showed strong evidence of model Φ2 (indicated by marginal likelihood), which integrates current and recent hydrology in its formulation, and lower prediction errors (indicated by RMSE and ME). Models Φ1 and Φ2 better described wash-off dynamics compared to model Φ0, due to the inclusion of one or several hydrological descriptors.From March 2011 to March 2015, model Φ2 estimated 137Cs export from Niida catchment between 0.32 and 0.67 TBq, with a median value of 0.49 TBq, which represents around 0.27% of the initial fallout and could represent a significant source-term to the Ocean compared to the direct release from Fukushima Dai-ichi Nuclear Power Plant (FDNPP). Moreover the remaining 99% of the initial radiocesium fallout within the catchment may constitute a persistent contamination source for wash-off.Although the proposed methodology brought improvements in the assessment of wash-off fluxes, it remains an empirical interpolation method with a limited predictive power, particularly for recent low activities. To improve predictions, modelling approaches require more observed data (particularly more activity values corresponding to more hydrological conditions), and the inclusion of more hydrological descriptors.



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Detection in subsurface air of radioxenon released from medical isotope production

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Publication date: Available online 11 November 2016
Source:Journal of Environmental Radioactivity
Author(s): Christine Johnson, Steven Biegalski, Derek Haas, Justin Lowrey, Theodore Bowyer, James Hayes, Reynold Suarez, Michael Ripplinger
In order to better understand potential backgrounds of Comprehensive-Nuclear Test-Ban Treaty on-site inspection relevant gases, a sampling campaign was performed near Canadian Nuclear Laboratories in the Ottawa River Valley, a major source of environmental radioxenon. First of their kind measurements of atmospheric radioxenon imprinted into the shallow subsurface from an atmospheric pressure driven force were made using current on-site inspection techniques. Both atmospheric and subsurface gas samples were measured and analyzed to determine radioxenon concentrations. These measurements indicate that under specific sampling conditions, on the order of ten percent of the atmospheric radioxenon concentration may be measured via subsurface sampling.



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Calif. county provides body armor for EMS personnel, firefighters

Officials used a $150,000 grant to purchase 152 ballistic vests for first responders.

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Intraocular pressure and cerebral oxygenation during prolonged headward acceleration

Abstract

Purpose

Supra-tolerance head-to-foot directed gravitoinertial load (+Gz) typically induces a sequence of symptoms/signs, including loss of: peripheral vision—central vision—consciousness. The risk of unconsciousness is greater when anti-G-garment failure occurs after prolonged rather than brief exposures, presumably because, in the former condition, mental signs are not consistently preceded by impaired vision. The aims were to investigate if prolonged exposure to moderately elevated +Gz reduces intraocular pressure (IOP; i.e., improves provisions for retinal perfusion), or the cerebral anoxia reserve.

Methods

Subjects were exposed to 4-min +Gz plateaux either at 2 and 3 G (n = 10), or at 4 and 5 G (n = 12). Measurements included eye-level mean arterial pressure (MAP), oxygenation of the cerebral frontal cortex, and at 2 and 3 G, IOP.

Results

IOP was similar at 1 (14.1 ± 1.6 mmHg), 2 (14.0 ± 1.6 mmHg), and 3 G (14.0 ± 1.6 mmHg). During the G exposures, MAP exhibited an initial prompt drop followed by a partial recovery, end-exposure values being reduced by ≤30 mmHg. Cerebral oxygenation showed a similar initial drop, but without recovery, and was followed by either a plateau or a further slight decrement to a minimum of about −14 μM.

Conclusion

Gz loading did not affect IOP. That cerebral oxygenation remained suppressed throughout these G exposures, despite a concomitant partial recovery of MAP, suggests that the increased risk of unconsciousness upon G-garment failure after prolonged +Gz exposure is due to reduced cerebral anoxia reserve.



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Indocyanine green fluorescence-navigated robotic segmentectomy

Abstract

Background

Pulmonary segmentectomy with radical lymphadenopathy has been considered effective to manage small primary lung cancers [1, 2]. This procedure provides the advantages of minimal invasive surgery and is reported sufficient for safe margin. However, segmentectomy is more difficult to be performed than lobectomy because intersegmental plane cannot be detected easily. Several methods have been reported for identifying the actual intersegmental plane [37], but the sensitivity of these methods is limited to the lung conditions like patients with emphysematous lung and needed skilled surgeon to perform. We demonstrated the technique of visualizing the intersegmental plane via fluorescence navigated with indocyanine green (ICG) injection intravenously during robotic S6 segmentectomy.

Methods

This video presents a case that 70-year-old male who has past history of rectal cancer status post-LAR in 1991, HCC status post-RFA, and hepatitis C was found a lung nodule over superior segment of left lower lobe during regular examination. The nodule was considered metastatic tumor preoperatively. The segmental pulmonary artery and pulmonary bronchus to superior segment of left lower lobe were ligated firstly, and the intersegmental plane was seen clearly after ICG injection intravenously under fluorescence navigated. Intersegmental plane was marked by electrocautery, and then, the target segment was resected by endostapler.

Results

Patient tolerated the procedure well. Chest tube was removed by postoperative day 3, and he was discharged smoothly by postoperative day 5. There were no complications. Postoperative chest X-ray revealed good lung expansion. Not as preoperative expectation, the final pathology was consistent with caseating granulomatous inflammation.

Conclusion

It is difficult to identify intersegmental plane during segmentectomy. ICG fluorescence-navigated segmentectomy provides immediate visualization of the intersegmental plane and makes the procedure easy and fast.



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Timing of cholecystectomy following endoscopic sphincterotomy: a population-based study

Abstract

Background

Choledocholithiasis is commonly treated initially with endoscopic sphincterotomy, followed by cholecystectomy to definitively address the underlying problem of cholelithiasis. While the benefits of early cholecystectomy have been realized in other populations, the preferred timing for this subset of patients is less well established. We performed a large, population-based analysis to determine the frequency, benefits, and practice variance in regard to early cholecystectomy on a provincial level.

Methods

Patients undergoing endoscopic sphincterotomy followed by cholecystectomy in British Columbia, Canada, from January 2001 to December 2011 were identified using fee-code billing data. Multiple databases were linked to obtain information on demographics, admissions, procedures, mortality, and census geographic data. Regression analysis was performed for length of stay (LOS) and additional procedures. Outcome data were risk adjusted for age, gender, comorbidities, socioeconomic status, and year of procedure. Variability of early cholecystectomy crude rates across census areas was determined using a funnel plot.

Results

There were 4287 eligible patients. Of these, 1905 (44.4%) underwent early cholecystectomy, defined as surgery within 14 days of sphincterotomy. Median interval to cholecystectomy was 2 days for the early cholecystectomy group and 61 days for delayed. There was a significant difference in hospital LOS favoring early cholecystectomy for patients with documented gallstone disease (p < 0.05). Patients initially admitted to a surgical service were more likely to undergo early cholecystectomy (60 vs. 36%, p < 0.001). There was no difference between groups in terms of bile duct injury or mortality. There was wide variability in rates of early cholecystectomy among census areas (range 0–96%) and health regions (range 20–66%) which was not explained by population density or geography.

Conclusion

Early cholecystectomy is the ideal approach to gallstone disease post-sphincterotomy. Despite this, a large amount of clinical variance exists in regard to timing of cholecystectomy which seems to be primarily institution dependent.



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Transoral endoscopic thyroidectomy vestibular approach with intraoperative nerve monitoring

Abstract

Background

Transoral endoscopic thyroidectomy by a vestibular approach (TOETVA) is a novel technique for thyroid gland excision. Compared to the transaxillary endoscopic and bilateral axillo-breast approaches, which require substantial dissection to reach the thyroid gland, TOETVA provides the most direct access to the target organ.

Methods

The aim of this video is to provide a step-by-step overview of TOETVA and demonstrate how to set up and utilize intraoperative nerve monitoring.

Results

Three incisions are placed in the vestibular region of the oral cavity just below the lower lip for placement of 2 lateral 5-mm trocars and 1 centrally placed 11-mm trocar. Insufflation to 6 mm Hg is used to maintain the working spacing. Using a 2-handed technique and triangulation, the thyroid gland is mobilized, taking care to identify and preserve the relevant cervical anatomy.

Conclusion

TOETVA is safe and feasible and provides an excellent cosmetic outcome with the most confidentially compared to the other remote access endoscopic approaches.



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EUS-guided gastroenterostomy is comparable to enteral stenting with fewer re-interventions in malignant gastric outlet obstruction

Abstract

Background and aims

Endoscopic enteral stenting (ES) in malignant gastric outlet obstruction (GOO) is limited by high rates of stent obstruction. EUS-guided gastroenterostomy (EUS-GE) is a novel procedure that potentially offers sustained patency without tumor ingrowth/overgrowth. The aim of this study is to compare EUS-GE with ES in terms of (1) symptom recurrence and need for re-intervention, (2) technical success (proper stent positioning as determined via endoscopy and fluoroscopy), (3) clinical success (ability to tolerate oral intake without vomiting), and (4) procedure-related adverse events (AEs).

Methods

Multicenter retrospective study of all consecutive patients who underwent either EUS-GE at four centers between 2013 and 2015 or ES at one center between 2008 and 2010.

Results

A total of 82 patients (mean age 66-years ± 13.5 and 40.2% female) were identified: 30 in EUS-GE and 52 in ES. Technical and clinical success was not significantly different: 86.7% EUS-GE versus 94.2% ES (p = 0.2) and 83.3% EUS-GE versus 67.3% ES (p = 0.12), respectively. Symptom recurrence and need for re-intervention, however, was significantly lower in the EUS-GE group (4.0 vs. 28.6%, (p = 0.015). Post-procedure mean length of hospitalization was comparable at 11.3 days ± 6.6 for EUS-GE versus 9.5 days ± 8.3 for ES (p = 0.3). Rates and severity of AEs (as per the ASGE lexicon) were also similar (16.7 vs. 11.5%, p = 0.5). On multivariable analysis, ES was independently associated with need for re-intervention (OR 12.8, p = 0.027).

Conclusion

EUS-GE may be ideal for malignant GOO with comparable effectiveness and safety to ES while being associated with fewer symptom recurrence and requirements for re-intervention.



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Laparoscopic adrenalectomy by transabdominal lateral approach: 20 years of experience

Abstract

Background

Laparoscopic adrenalectomy (LA) has become the standard technique for most indications. The aim of this study was to determine the predictive factors of intra- and postoperative complications in order to inform the orientation of patient to a surgeon with more experience in adrenal surgery.

Methods

From January 1994 to December 2013, 520 consecutive patients benefited from LA at Huriez Hospital, Lille, France. Each complication was graded according to the Dindo–Clavien-grade scale. The predictive factors of complications were determined by logistic regression.

Results

Fifty-two surgeons under the supervision of 5 senior surgeons (individual experience >30 LA) participated. Postoperative complications with a grade of ≥2 occurred in 52 (10 %) patients (29 (5.6 %) medical, 19 (3.6 %) surgical, and 4 (0.8 %) mixed complications) leading to 12 (2.3 %) reoperations. There was no postoperative death. Intraoperative complication happened in 81 (15.6 %) patients responsible for conversion to open adrenalectomy (OA) [odds ratio (OR) 13.9, CI 95 % 4.74–40.77, p < 0.001]. History of upper mesocolic or retroperitoneal surgery was predictive of intraoperative complication (OR 2.02, 1.05–3.91, p = 0.036). Lesion diameter ≥45 mm was predictive of intraoperative complication (OR 1.94, 1.19–3.15, p = 0.008), conversion to OA (OR 7.46, 2.18–25.47, p = 0.001), and adrenal capsular breach (OR 4.416, 1.628–11.983, p = 0.004). Conversion to OA was the main predictive factor of postoperative complications (OR 5.42, 1.83–16.01, p = 0.002). Under adequate supervision, the surgeon's individual experience and initial adrenal disease were not considered predictive of complications.

Conclusion

Lesion diameter over 45 mm is the determinant parameter for guidance of patients to surgeons with more extensive experience.



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Ten years in the dump: An updated review of the Miocene primate-bearing localities from Abocador de Can Mata (NE Iberian Peninsula)

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Publication date: January 2017
Source:Journal of Human Evolution, Volume 102
Author(s): David M. Alba, Isaac Casanovas-Vilar, Miguel Garcés, Josep M. Robles
More than ten years of paleontological fieldwork during the enlargement of the Can Mata Landfill (Abocador de Can Mata [ACM]), in els Hostalets de Pierola (Vallès-Penedès Basin, NE Iberian Peninsula) led to the recovery of >60,000 Miocene vertebrate remains. The huge sampling effort (due to continuous surveillance of heavy machinery digging activity, coupled with manual excavation and screen-washing of sediments) enabled generally rare faunal elements such as pliopithecoid and hominoid primates to be found. Thanks to detailed litho-, bio- and magnetostratigraphic controls, accurate dating is possible for all the recovered primate remains from 19 of the 235 localities defined along the 234 m-thick composite stratigraphic sequence of the ACM. Here we report updated estimated (interpolated) ages for these paleontological localities and review the timing of the primate succession in this area. Our results indicate that the whole ACM sequence is late Aragonian in age (MN6 and MN7+8) and includes seven magnetozones that are correlated to subchrons C5Ar.1r to C5r.2r (ca. 12.6 to 11.4 Ma). Great apes (dryopithecines) are first recorded at 12.4–12.3 Ma, but most of the finds (Anoiapithecus, Pierolapithecus and Dryopithecus) cluster between 12.0 and 11.9 Ma, followed by some indeterminate dryopithecine remains between 11.7 and 11.6 Ma. Pliopithecoids first appear at 12.1 Ma, being subsequently represented by Pliopithecus between 11.9 and 11.7 Ma. The small-bodied hominoid Pliobates is the youngest ACM primate, with an estimated age of 11.6 Ma. Although these primates probably overlapped in time, their co-occurrence is recorded only twice, at 11.9 Ma (a dryopithecine with Pliopithecus) and at 11.6 Ma (a dryopithecine with Pliobates). The rare co-occurrence between great apes and small-bodied catarrhines might be attributable to sampling biases and/or to presumed diverging ecological preferences of these groups. In the future, more detailed analyses of the fauna recovered from the long and densely-sampled ACM sequence will hopefully throw new light on this long-standing, unresolved question.



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Small mammal utilization by Middle Stone Age humans at Die Kelders Cave 1 and Pinnacle Point Site 5-6, Western Cape Province, South Africa

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Publication date: December 2016
Source:Journal of Human Evolution, Volume 101
Author(s): Aaron Armstrong
Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations. Based on comparisons with control assemblages of known accumulation, it is evident that humans accumulated many of the Cape dune mole-rats, hares, and size 1 bovids at DK1. The patterning of cut-marked and burned mole-rat remains at DK1 provides evidence in the MSA for the systematic utilization of small mammals for their skins and as a protein source. Unlike DK1, small mammals and size 1 bovids constitute only a small portion of the PP5-6 mammals and they exhibit little evidence of human accumulation. Nocturnal and diurnal raptors accumulated most of the small fauna at PP5-6. The nominal presence of small mammals in the PP5-6 fauna is atypical of MSA sites in the Cape Floristic Region, where they are abundant and often constitute large portions of MSA archaeofaunas. DK1 humans maximized the environmental yield by exploiting low-quality resources, a strategy employed possibly in response to localized environmental conditions and to greater human population densities. In comparison, the MIS5-4 humans at PP5-6 did not exploit small mammals and instead focused on higher-quality resources like shellfish and large ungulates. Humans and predators accumulated few small mammals at PP5-6, suggesting that these taxa may have been less abundant near the site and/or that humans could afford to concentrate on high-quality resources, perhaps because of a higher-yield local environment. This study suggests that an adaptive response to the environmental conditions of MIS4 was to maximize the resource yield of local habitats to include lower-quality resources when necessary. The incorporation of these resources in the face of changing environmental and perhaps population pressures is a subsistence adaptation that played a crucial role in the population stability and expansion evidenced by the number of sites in the Cape dating to MIS4.



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Sepsis and Capnography

Learn the importance of Capnography as an essential tool for the early recognition of sepsis in the filed.

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Sepsis and Capnography

Learn the importance of Capnography as an essential tool for the early recognition of sepsis in the filed.

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Sepsis and Capnography

Capnography is an essential tool for the early recognition of sepsis in the filed.

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Sepsis and Capnography

Capnography is an essential tool for the early recognition of sepsis in the filed.

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What if President Trump made EMS a priority?

In 2009, after hearing about a vacationing EMS colleague who responded to an in-flight medical emergency, I had an idea about formalizing an arrangement between off-duty paramedics and commercial airlines, whereby medics would fly first class in return for their vigilance en route. I was so enthusiastic about wider seats — I mean the chance to help — I wrote to the guy in charge. Of the country. Who better to coax the FAA than POTUS"

The then-new President must have been busy studying sub-Saharan trade agreements, because I got one of those machine-generated replies that didn't even mention my scheme. It just said something about our nation facing "serious challenges," which I took to mean fire departments running EMS.

Here we are almost eight years later and there's been no progress on my paramedic passenger plan. With a new administration coming into office in January, I'd like to expand my original proposal to seven EMS initiatives for President Trump to address within 100 days of taking office.

I was going to say 90 days, but I want to leave enough time for the First Family to get settled in the White House, change the wallpaper, learn to work the alarm system and find a good Chinese restaurant.

I'm kidding about the Chinese restaurant, but serious about these suggestions:

1. Medics get travel perks for being on duty during commercial flights
This was my original idea. We'd sign in at the gate, show evidence of certification, maybe get a quick in-service on equipment and procedures, then relax in seats much more soothing to our decrepit lumbar areas. On rare occasions when we're needed, we'd answer the call with other medical professionals who'd be eligible for the same perks.

I doubt any of us would be summoned as often as my brother, Jeff, an EMT who flies a lot for business. Jeff says he's witnessed about 15 in-flight medical emergencies during his travels. I'm pretty sure that's a coincidence, but the AHA has considered downgrading Jeff's mere presence on an airplane to Class III – potentially harmful.

2. Replace fun facts from the national curriculum with an hour or two of algebra, psychology or self-defense
I'd like to see us cull out superficial material, like the pros and cons of horse drawn ambulances, that has a low return on time invested. Educators could reduce time spent on the history of EMS, radio technology and ambulance design and cover broader topics more valuable to street-level personnel.

Algebra shouldn't be an issue for high-school graduates, but it is. I haven't met too many medics who are comfortable even with fractions and decimals. Unless we want our responders to rely on contrived shortcuts like "Midnight Rules" and the "Lidocaine Clock" to calculate drug doses, we're going to have to offer supplementary instruction in basic math.

3. A radio distress signal for EMS providers
We need a universal way to stealthily alert headquarters that the situation is definitely not 10-4. In New York City, the distress signal is 10-13.

Not everyone uses ten codes anymore, so maybe a secret, absurd word or phrase would be better – something like, "Bring me the spare MAST trousers."

4. Required rest periods like airline pilots have
Society has already conceded that people who fly airplanes need sleep. Shouldn't there be similar concerns about EMS providers doing invasive procedures or driving ambulances after 24 hours without rest" I propose agencies mandate three hours of sleep for every 18 hours worked.

I'm remembering how I used to feel around midnight after running calls since 0700. I might get by on adrenalin around 1 or 2 a.m., but I wouldn't want me treating me between 0300 and 0500 without any sleep since the previous sunrise.

5. Background checks that are at least as thorough for prospective EMS employees as for handgun buyers
How conscientious do we want to be about hiring people who play well with others" Many EMS agencies are thorough about investigating prospective employees, but some treat the application process as a superficial exercise that merely maximizes the candidate pool and minimizes delays in getting new hires on the truck.

Take a look at the federal Firearm Transaction Record for over-the-counter sales (ATF Form 4473). Verifying the "No" answers to questions about criminal behavior, substance abuse, mental disorders and dishonorable discharges should be a no-brainer for EMS, too. I'd also check applicants' Facebook posts for sociopathic musings.

6. A national superset of treatment protocols
Some EMS systems take years to embrace well-documented improvements to treatment modalities. What if agencies could create or supplement local protocols from a national bank of vetted practices — the latest ACLS algorithms, for example" I could see that approach leading to fewer regional differences based solely on subjective preferences.

7. Incentives for younger semi-retirees in good health to join EMS
This is the one I'm most excited about. There are lots of successful, middle-aged individuals out there who've been able to cut back on their work hours due to good fortune. Some of those folks would be superior caregivers with lots more life experience than the average medic or EMT. I'd love to see a national initiative that channels healthy and properly motivated mid-lifers into EMS.

That's my list. I'll give the new President a chance to establish world peace, then forward these suggestions with my resume.

What would you add"



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Inside EMS Podcast: 4 tips to be more professional in EMS

Download this podcast on iTunes, SoundCloud or via RSS feed

​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss professionalism on the job. From the way you talk to patients, dress, and keep your ambulance, it all culminates into developing your professional credibility. Have other tips to add" Join the discussion and sound off in the comments.



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Trump wins: The elephant in the fire, EMS dayroom

There are a great many more questions than answers surrounding what President-elect Trump will do once he takes office next January.

And there's good reason for this.

His campaign was light on policy details. And when details were shared, they were often criticized as undoable by liberal, moderate and conservative subject experts.

There's also the gulf separating what candidates say on the campaign trail and what they do in the oval office — regardless of the party they represent.

The questions from the campaign about how a President Trump would influence the fire service are the same as they were in July. The issues of grant funding, firefighter health and safety, wildland fire protection and medical call volume and billing are still big question marks. You can toss into that mix the future roles of such agencies as FEMA and the U.S. Fire Administration.

But the real elephantine question in the room is how will the Trump administration and the new Congress impact the U.S. and global economies" That outcome may well dictate how the other issues play out — as the head goes, so goes the body.

The Great Recession that we are still recovering from hit fire departments especially hard. Drops in municipal tax income led to career departments laying off firefighters and leaving vacancies unfilled. Some volunteer departments had to close shop over lost funding.

Departments also delayed purchasing everything from new fire stations, to rigs, all the way down to needed turnout gear. And many of them eliminated or reduced services like fire prevention and fire inspections.

Worst-case scenario
These cutbacks all negatively impact firefighters' ability to come home safe after each call and effectively protect their communities.

Compounding recessionary funding cuts are increases in calls for service. Recessions push those households who are just getting by into poverty. And this is an equal-opportunity force that doesn't care if the household is in a rural or urban setting.

Studies show a correlation between poverty and increased use of EMS, risk of urban fires, risk of rural fires and risk of wildland-urban interface fires. Increased poverty will also lead to more crime and more civil unrest, both put firefighters and medics at greater peril and drain precious resources.

To be clear, a Trump victory does not guarantee a new recession. There are way too many factors in play to make that call.

We don't know what his cabinet will look like, how much he will listen to his advisors, what his priorities will be or how he will work with Congress. We don't know who will sit at the head of key Senate and House committees. And we don't know if the economic plans he puts in motion will work.

Yet several economists, including those from the libertarian Cato Institute and the conservative-leaning American Enterprise Institute, fear that if Trump is able to push through much of what he proposed on the campaign trail, a new recession is inevitable.

In short, they say that his proposed high tariffs would kick off a trade war and that massive tax cuts without spending cuts — coupled with major infrastructure and military spending — would lead to huge deficits and debt.

Some believe the massive infrastructure spending and tax cuts will provide economic growth — similar to stimulus measures used during our last recession. But, they say, that growth is likely to be temporary.

How the short- and long-term economy plays out under our newly elected government isn't the only question firefighters need to concern themselves with, but it is the largest question.



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Marine-turned-paramedic explains career path decision

By Amanda Thames
The Daily News

JACKSONVILLE, N.C. — The First Responders Friday series is a weekly feature focusing on the men and women in law enforcement, emergency services and fire services who serve in our community every day.

Name: Owen Wood
Age: 32
Years served total: 2
Current place of employment: Haws Run Volunteer Rescue Squad (Volunteer); Pender EMS & Fire (Paid)
Rank or title: Haws Run VRS EMT; Pender EMS & Fire Paramedic

What made you decide on this career path?
My experiences in the U.S. Marine Corps allowed me to realize my affinity for medicine and my strengths in working under high stress conditions. I actually made the decision to transition from the military into the medical field when I was 30 years old and more than half of the way to a military retirement. This surely seemed like insanity to many, but surprisingly I had quite a bit of support from people. While I truly loved my time in the Marine Corps, I just knew there was more I wanted to do in my lifetime.

What is it you love about working in your community?
For me, working in my own community is exponentially rewarding because I can see the effects of my efforts firsthand. Building relationships with people locally is also a big contributing factor. In our relatively small community, there are so many people with such diverse experiences, and you can learn quite a bit from them. There have been many times when I have arrived on a scene to the residence of someone I know. It makes me feel good to see the look of relief on their face when I arrive, but it is also very sobering, knowing that they trust and depend on me in their time of need.

Describe some of your favorite experiences in your career.
While in paramedic school, students are required to complete a minimum of 500 clinical hours. During this time, I was very blessed to work under many excellent doctors, physician assistants, paramedics and nurses. Working with so many amazing people confirmed my decision to enter the medical field. I have also really enjoyed doing community fundraisers, such as our annual haunted hayride. Additionally, the general day to day unexpectedly hilarious situations are one of my favorite things about the job. These may include but are not limited to run-ins with wild or domesticated animals, apocalyptic-type weather at the worst possible times, etc.

Where else have you worked in the past? Describe the road to your current position.
On my 17th birthday I enlisted in the Marine Corps and attended recruit training shortly after graduating from high school. With several generations of my family serving in the Marine Corps, I knew from a young age that I wanted to follow in their footsteps. Following completion of infantry training, I was soon assigned to the Fleet Marine Forces, where I completed many combat and non-combat deployments. During my deployments, I would often find myself treating fellow Marines, civilians and other coalition forces when no Navy Corpsman was available. I treated illnesses and wounds from minor cuts and scratches to major multi-system trauma. These were the experiences that would ignite my passion for medicine, and particularly emergency medicine. After serving 12 years in the Marine Corps, I decided it was time for me to enter a new chapter in my life and pursue a career in medicine. Just before the end of my service, I joined Haws Run Volunteer Rescue Squad and am still an active member. I attended the EMT-Basic Course and shortly thereafter enrolled in the EMT-Paramedic program. I now work full-time as a paramedic for Pender EMS & Fire and have attained National Registry credentialing as a paramedic as well as credentialing as a Certified Flight Paramedic from the Board for Critical Care Transport Paramedic Certification. I am also a full-time college student majoring in biology with aspirations to attend the UNC School of Medicine at Chapel Hill.

What was the most memorable case you've worked?
During my relatively short time in EMS I have had so many memorable cases that it is hard to pick one in particular as the most memorable. While at work one day, I asked a good friend of mine, Sharla Sineath, a firefighter and EMT-Intermediate, for assistance. She said to me "write about the case that made you sure this is what you want to do." With that in mind, my answer would have to be every case. Every time a new call comes over the pager, no matter how simple or complex it may be, I always see the same thing — people helping people. The incredible amount of dedication and teamwork employed by EMS, fire and law enforcement on every single call with one goal, helping someone in their time of need, blows me away. It is truly a shining light of hope and reassures my faith in humanity.

What pushes you to stay on this career path and continue working in such a challenging profession?
I really enjoy the teamwork that comes with the profession as well as the daily interaction with so many different people. I enjoy the physical and intellectual challenges and no matter what, I know that no two days will be the same.

Any additional comments you'd like to include?
There have been so many different people that have helped and mentored me along the way, but I would never be where I am today without the support of my wonderful wife Tracie. She has been supportive of my career choices and is always there for me after a long shift or to help me with studying for class. She is also a volunteer EMT with Haws Run Rescue Squad and does a tremendous amount of fundraisers and community outreach.

Copyright 2016 The Daily News
All Rights Reserved



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Inside EMS Podcast: 4 tips to be more professional in EMS

Download this podcast on iTunesSoundCloud or via RSS feed

​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss professionalism on the job. From the way you talk to patients, dress, and keep your ambulance, it all culminates into developing your professional credibility. Have other tips to add? Join the discussion and sound off in the comments.



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What if President Trump made EMS a priority?

In 2009, after hearing about a vacationing EMS colleague who responded to an in-flight medical emergency, I had an idea about formalizing an arrangement between off-duty paramedics and commercial airlines, whereby medics would fly first class in return for their vigilance en route. I was so enthusiastic about wider seats — I mean the chance to help — I wrote to the guy in charge. Of the country. Who better to coax the FAA than POTUS?

The then-new President must have been busy studying sub-Saharan trade agreements, because I got one of those machine-generated replies that didn't even mention my scheme. It just said something about our nation facing "serious challenges," which I took to mean fire departments running EMS.

Here we are almost eight years later and there's been no progress on my paramedic passenger plan. With a new administration coming into office in January, I'd like to expand my original proposal to seven EMS initiatives for President Trump to address within 100 days of taking office.

I was going to say 90 days, but I want to leave enough time for the First Family to get settled in the White House, change the wallpaper, learn to work the alarm system and find a good Chinese restaurant.

I'm kidding about the Chinese restaurant, but serious about these suggestions:

1. Medics get travel perks for being on duty during commercial flights
This was my original idea. We'd sign in at the gate, show evidence of certification, maybe get a quick in-service on equipment and procedures, then relax in seats much more soothing to our decrepit lumbar areas. On rare occasions when we're needed, we'd answer the call with other medical professionals who'd be eligible for the same perks.

I doubt any of us would be summoned as often as my brother, Jeff, an EMT who flies a lot for business. Jeff says he's witnessed about 15 in-flight medical emergencies during his travels. I'm pretty sure that's a coincidence, but the AHA has considered downgrading Jeff's mere presence on an airplane to Class III – potentially harmful.

2. Replace fun facts from the national curriculum with an hour or two of algebra, psychology or self-defense
I'd like to see us cull out superficial material, like the pros and cons of horse drawn ambulances, that has a low return on time invested. Educators could reduce time spent on the history of EMS, radio technology and ambulance design and cover broader topics more valuable to street-level personnel.

Algebra shouldn't be an issue for high-school graduates, but it is. I haven't met too many medics who are comfortable even with fractions and decimals. Unless we want our responders to rely on contrived shortcuts like "Midnight Rules" and the "Lidocaine Clock" to calculate drug doses, we're going to have to offer supplementary instruction in basic math.

3. A radio distress signal for EMS providers
We need a universal way to stealthily alert headquarters that the situation is definitely not 10-4. In New York City, the distress signal is 10-13.

Not everyone uses ten codes anymore, so maybe a secret, absurd word or phrase would be better – something like, "Bring me the spare MAST trousers."

4. Required rest periods like airline pilots have
Society has already conceded that people who fly airplanes need sleep. Shouldn't there be similar concerns about EMS providers doing invasive procedures or driving ambulances after 24 hours without rest? I propose agencies mandate three hours of sleep for every 18 hours worked.

I'm remembering how I used to feel around midnight after running calls since 0700. I might get by on adrenalin around 1 or 2 a.m., but I wouldn't want me treating me between 0300 and 0500 without any sleep since the previous sunrise.

5. Background checks that are at least as thorough for prospective EMS employees as for handgun buyers
How conscientious do we want to be about hiring people who play well with others? Many EMS agencies are thorough about investigating prospective employees, but some treat the application process as a superficial exercise that merely maximizes the candidate pool and minimizes delays in getting new hires on the truck.

Take a look at the federal Firearm Transaction Record for over-the-counter sales (ATF Form 4473). Verifying the "No" answers to questions about criminal behavior, substance abuse, mental disorders and dishonorable discharges should be a no-brainer for EMS, too. I'd also check applicants' Facebook posts for sociopathic musings.

6. A national superset of treatment protocols
Some EMS systems take years to embrace well-documented improvements to treatment modalities. What if agencies could create or supplement local protocols from a national bank of vetted practices — the latest ACLS algorithms, for example? I could see that approach leading to fewer regional differences based solely on subjective preferences.

7. Incentives for younger semi-retirees in good health to join EMS
This is the one I'm most excited about. There are lots of successful, middle-aged individuals out there who've been able to cut back on their work hours due to good fortune. Some of those folks would be superior caregivers with lots more life experience than the average medic or EMT. I'd love to see a national initiative that channels healthy and properly motivated mid-lifers into EMS.

That's my list. I'll give the new President a chance to establish world peace, then forward these suggestions with my resume.

What would you add?



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SINGLE PASSIVE LEG MOVEMENT INDUCED-HYPEREMIA: A SIMPLE VASCULAR FUNCTION ASSESSMENT WITHOUT A CHRONOTROPIC RESPONSE

Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach which may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 second. During PLM, MAP transiently decreased (5±1 mmHg) while both HR and CO increased from baseline (6.0±1.1 bpm, and 0.8 ±0.01 l/min, respectively). Following sPLM, MAP fell similarly (5±2 mmHg; p=0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993±189 ml/min; 11.9±1.5 ml/min/mmHg, respectively) and sPLM (878±119 ml/min; 10.9±1.6 ml/min/mmHg, respectively). Thus, sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a, potentially confounding, chronotropic response, which may make sPLM more useful clinically.



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A Translational Cellular Model to Study the Impact of High Frequency Oscillatory Ventilation (HFOV) on Human Epithelial Cell Function

High frequency oscillatory ventilation (HFOV) has been proposed as gentle ventilation strategy to prevent lung injury in the preterm infant. High frequency ventilation leads to dimensional and mechanical airway deformation in animal airway models, which is consistent with translational studies demonstrating the impact of oxygen and biophysical stresses on normal airway cellular function. There is an overall paucity of clinical and cellular data on the impact of HFOV on the conducting airway. We developed an innovative method to test the impact of the clinical HFO Ventilator (Sensormedic 3100A) on human epithelial cell function. In this translational model, we were able to study the differential effects of biophysical stress due to HFOV independently and in combination with hyperoxia on a direct cellular level of the conducting airway system. Additionally, we could demonstrate that hyperoxia and pressure by HFOV independently resulted in significant cell dysfunction and inflammation, while the combination of HFOV and hyperoxia had an additive effect resulting in cell death.



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Habitual aerobic exercise does not protect against micro- or macrovascular endothelial dysfunction in healthy estrogen-deficient postmenopausal women

Aging causes micro- and macrovascular endothelial dysfunction, as assessed by endothelium-dependent dilation (EDD), which can be prevented and reversed by habitual aerobic exercise (AE) in men. However, in estrogen-deficient postmenopausal women, whole forearm microvascular EDD hasn't been studied, and a beneficial effect of AE on macrovascular EDD hasn't been consistently shown. We assessed forearm blood flow in response to brachial artery infusions of acetylcholine (FBFACh), a measure of whole forearm microvascular EDD, and brachial artery flow-mediated dilation (FMD), a measure of macrovascular EDD, in 12 premenopausal sedentary women (Pre-S; 24±1 yrs; VO2max=37.5±1.6 ml/kg/min), 25 estrogen-deficient postmenopausal sedentary women (Post-S; 62±1 yrs; VO2max=24.7±0.9 ml/kg/min), and 16 estrogen-deficient postmenopausal AE-trained women (Post-AE; 59±1 yrs; VO2max=40.4±1.4 ml/kg/min). FBFACh was lower in Post-S and Post-AE compared with Pre-S women (135±9 and 116±17 vs.193±21 AUC, respectively, both P<0.008), whereas Post-S and Post-AE women weren't different (P=0.3). Brachial artery FMD was 34% (5.73±0.67%) and 45% (4.79±0.57%) lower in Post-S and Post-AE, respectively, vs. Pre-S women (8.69±0.95%, both P≤0.01), but not different between Post-S and Post-AE women (P=0.3). Post-AE women had lower circulating C-reactive protein and oxidized low-density lipoprotein compared with Post-S women (0.5±0.1 vs. 1.1±0.2 mg/L and 40±4 vs. 55±3 U/L, respectively, both P=0.01), but these markers weren't correlated to FBFACh (P=0.3) or brachial artery FMD (P=0.8). These findings are consistent with the idea that habitual AE doesn't protect against age/menopause-related whole forearm micro- and macrovascular endothelial dysfunction in healthy non-obese estrogen-deficient postmenopausal women, despite being associated with lower systemic markers of inflammation and oxidative stress.



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Resistance training with instability is more effective than resistance training in improving spinal inhibitory mechanisms in Parkinson's disease

Background: This study assessed: 1) the effects of 12 weeks of resistance training (RT) and resistance training with instability (RTI) on presynaptic inhibition (PSI) and disynaptic reciprocal inhibition (DRI) of patients with Parkinson's disease (PD); 2) the effectiveness of RT and RTI in moving PSI and DRI values of patients towards values of age-matched healthy controls (HC [Z-score analysis]); and 3) associations between PSI and DRI changes and clinical outcomes changes previously published. Methods: Thirteen patients in RT group, 13 in RTI group, and 11 in a non-exercising control group completed the trial. While RT and RTI groups performed resistance exercises twice a week for 12 weeks, only the RTI group used unstable devices. Soleus H-reflex was used to evaluate resting PSI and DRI before and after experimental protocol. The HC (n=31) was assessed at pre-test only. Results: There were significant groupxtime interactions for PSI (P<0.0001) and DRI (P<0.0001). RTI was more effective than RT in increasing the levels of PSI (P=0.0154) and DRI (P<0.0001) at post-training and in moving PSI (Confidence interval [CI] 0.1-0.5) and DRI (CI 0.6-1.1) levels to those observed in HC. There was association between DRI and quality of life changes (r=-0.69, P=0.008) and a strong trend toward association between PSI and postural instability changes (r=0.60, P=0.051) after RTI. Conclusions: RTI increased PSI and DRI levels more than RT, reaching the average values of the HC. Thus, RTI may cause plastic changes in PSI and DRI pathways that are associated with some PD clinical outcomes.



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Drosophila ubiquitin E3 ligase dSmurf is required for synapse remodeling and axon pruning by glia

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Publication date: Available online 11 November 2016
Source:Journal of Genetics and Genomics
Author(s): Changyan Chen, Shuai Yin, Wenze Cao, Margaret S. Ho




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Comparison of the efficiency of the nebulization of salbutamol, epinephrine and normal saline on treatment of bronchiolitis

2016-11-11T05-36-50Z
Source: International Journal of Research in Medical Sciences
Rakotomalala Rivo Lova Herilanto, Lovaniaina Ravelomanana, Andriatahirintsoa Emilson J. P. R., Tsifiregna Rosa Lalao, Ravelomanana Noeline.
Background: Bronchiolitis is a frequent cause of hospitalization. Despite the frequency of this pathology, there is not a single, widely practiced evidence-driven treatment especially using of nebulization. Present purpose was to compare which is efficient: nebulized salbutamol, epinephrine or normal saline. Methods: We have preceded to a prospective study from January 1st 2011 to March 31st 2012 including children between 29 days old and 2 years old. Results: We have included 90 patients divided in three groups and received nebulized salbutamol, epinephrine or normal saline. There was no real difference in the variables of the groups: clinical score, oxygen saturation, heart rate, temperature and weight but the hospitalization duration was shorter in the group who have been cured by normal saline Conclusions: This study shows that salbutamol, epinephrine and normal saline can be used in the same situation but the normal saline has more advantages because of his low coast and the absence of risk of side effects.


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A comparative study between the efficacies of betadine scrub (10%) versus alcohol based hand rub in preoperative hand disinfection

2016-11-11T05-36-50Z
Source: International Journal of Research in Medical Sciences
Rahul Kadam, Chinmoy Sharma, Abhaykumar Chhallani, Sunil Yadav.
Background: Hand hygiene is a crucial measure for preventing healthcare-related infections. Surgical scrub is an important factor in the safety and success of a surgical operation. The aim of this study was to comparatively evaluate effectiveness of povidone iodine scrub (10%) and alcohol based hand rubs (Sterilium). Methods: Single centre, double blinded, comparative study performed over a period of 6 months in MGM Medical College and hospital. Sampling was conducted, after the surgeons participating had used either technique for preoperative hand disinfection. Colonies were counted after 48 hours of aerobic incubation at 37°C. Positive cultures were identified and their frequencies were compared. Data were summarized using descriptive statistical methods. Comparison of counts between groups was performed using Chi square test. Results: From the 100 obtained samples, there was higher number of positive growth in Sterilium as compared to povidone iodine scrub (14% versus 8%) though statistically not significant. Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter was the most common organism isolated in both the groups. Conclusions: Povidone-iodine is more efficacious than that of alcohol-based solutions in preoperative hand disinfection


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Homozygous variants in pyrroline-5-carboxylate reductase 2 (PYCR2) in patients with progressive microcephaly and hypomyelinating leukodystrophy

Pyrroline-5-carboxylate reductase 2, encoded by PYCR2, is one of the three homologous enzymes that catalyze the last step of proline synthesis. Homozygous variants in PYCR2 have been reported in patients from multiple consanguineous families with hypomyelinating leukodystrophy 10 (HLD10) (MIM: 616420). Here, we report five additional patients from three families with homozygous nonsense or missense variants in PYCR2, identified through clinical exome sequencing. All patients presented with postnatally acquired microcephaly, moderate to profound global developmental delay, and failure to thrive. Brain MRI in these patients showed thin corpus callosum, delayed myelination, and generalized white-matter volume loss. Additional phenotypes that were less consistent among patients included seizures or seizure-like movements, spasticity and ataxic gait, recurrent vomiting, cortical blindness, dysmorphic features, joint contractures, and irritability. Exome sequencing identified homozygous variants in PYCR2 in the proband from each family: c.28C>T (p.(Glu10Ter)), c.796C>T (p.(Arg266Ter)), and c.577G>A (p.(Val193Met)). Subsequent targeted analyses demonstrated co-segregation of the disease with the variant in the family. Despite the metabolic role of PYCR2, routine serum metabolic test in these patients were normal. To further understand the disease etiology and functions of PYCR2, small molecule metabolomics profiling was performed in plasma from three severely affected patients. No significant changes were identified in proline biosynthesis pathway or related metabolites. Studying the clinical features and the metabolic profiles of the PYCR2-deficient patients provides a more comprehensive picture for this newly identified disorder and facilitates further research on the gene function and disease etiology. © 2016 Wiley Periodicals, Inc.



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Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy

Despite considerable progress in identifying causal genes for lipodystrophy syndromes, the molecular basis of some peculiar adipose tissue disorders remains obscure. In an Israeli–Arab pedigree with a novel autosomal recessive, multiple symmetric lipomatosis (MSL), partial lipodystrophy and myopathy, we conducted exome sequencing of two affected siblings to identify the disease-causing mutation. The 41-year-old female proband and her 36-year-old brother reported marked accumulation of subcutaneous fat in the face, neck, axillae, and trunk but loss of subcutaneous fat from the lower extremities and progressive distal symmetric myopathy during adulthood. They had increased serum creatine kinase levels, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Exome sequencing identified a novel homozygous NC_000019.9:g.42906092C>A variant on chromosome 19, leading to a NM_005357.3:c.3103G>T nucleotide change in coding DNA and corresponding p.(Glu1035*) protein change in hormone sensitive lipase (LIPE) gene as the disease-causing variant. Sanger sequencing further confirmed the segregation of the mutation in the family. Hormone sensitive lipase is the predominant regulator of lipolysis from adipocytes, releasing free fatty acids from stored triglycerides. The homozygous null LIPE mutation could result in marked inhibition of lipolysis from some adipose tissue depots and thus may induce an extremely rare phenotype of MSL and partial lipodystrophy in adulthood associated with complications of insulin resistance, such as diabetes, hypertriglyceridemia and hepatic steatosis. © 2016 Wiley Periodicals, Inc.



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Does attenuated skin blood flow lower sweat rate and the critical environmental limit for heat balance during severe heat exposure?

Attenuated skin blood flow (SkBF) is often assumed to impair core temperature (Tc) regulation. Profound pharmacologically-induced reductions in SkBF (∼85%) lead to impaired sweating but whether the smaller attenuations in SkBF (∼20%) more associated with ageing and certain diseases lead to decrements in sweating and maximum heat loss potential is unknown. Seven healthy males (28 ± 4y) completed a 30-min equilibration period at 41°C and a vapour pressure (Pa) of 2.57 kPa followed by incremental steps in Pa of 0.17 kPa every 6-min to 5.95 kPa. Differences in heat loss potential were assessed by identifying the critical vapour pressure (Pcrit) at which an upward inflection in Tc occurred. Three separate treatments elicited changes in plasma volume to achieve three distinct levels of SkBF: control (CON), diuretic-induced iso-osmotic dehydration to lower SkBF (DEH), and continuous saline infusion to maintain SkBF (SAL). Tc, mean skin temperature (Tsk), heart rate, mean laser-Doppler flux (forearm, thigh; LDFmean), mean local sweat rate (forearm, thigh; LSRmean), and metabolic rate were measured. In DEH, a 14.2 ± 5.7% lower plasma volume resulted in a ∼20% lower LDFmean (DEH: 139 ± 23, CON: 176 ± 22, SAL: 186 ± 22 PU; P = 0.034). However, LSRmean and whole-body sweat losses were unaffected by treatment throughout (P > 0.482). Pcrit for Tc was similar between treatments (CON: 5.05 ± 0.30, DEH: 4.93 ± 0.16, SAL: 5.12 ± 0.10 kPa; P = 0.166). Further, no differences were observed in the Tsk-Ta gradient, metabolic rate, or changes in Tc (P > 0.197). In conclusion, a ∼20% reduction in SkBF alters neither sweat rate nor the upper limit for heat loss from the skin during non-encapsulated passive heat stress.

This article is protected by copyright. All rights reserved



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Putative tissue location and function of the SLC5 family member SGLT3

Sodium glucose transporter 3 (SGLT3) has attracted interest because of its putative role as a glucose sensor, rather than a sugar transporter, in contrast to its SGLT1 and SGLT2 co-family members. Significant progress has been made in characterizing the electrophysiological properties in vitro of the single human SGLT3 isoform and the two mouse isoforms, SGLT3a and SGLT3b. Although early reports indicated SGLT3 expression in the small intestinal myenteric and submucosal neurones, hypothalamic neurones, portal vein, and kidney, a lack of reliable antibodies has left unanswered its exact tissue and cellular localization. Several hypotheses for a role of SGLT3 in glucose sensing, gastric emptying, GLP-1 release, and post-Roux en-Y gastric bypass remodelling have been explored, but so far there is only limited and indirect supportive evidence using non-specific agonists/antagonists, but with no firm conclusions. There are no published or available data in knockout animals and translation is difficult because of its different isoforms in human versus rodent, as well as a lack of selective agonists or antagonists, all making SGLT3 challenging to study. However, its unique electrophysiological properties, ubiquitous expression at the mRNA level, enrichment in the small intestine, and potential, but uncertain, physiological role demand more attention. The purpose of this overview and review of SGLT3 biology is to provide an update, highlight the gaps in our knowledge, and try to signpost potential ways forward to define its likely function in vivo.

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Sweating responses to isometric handgrip exercise and forearm muscle metaboreflex in prepubertal children and elderly

The purpose of the present study is to investigate sweating responses to isometric handgrip (IH) exercise and muscle metaboreflex in prepubertal children and the elderly. In hot condition (ambient temperature, 35°C; relative humidity, 45%), 13 healthy young adults, 10 prepubertal children, and 10 elderly (age: 20.4±1.2, 11.4±0.5, and 63.5±3.1 years, respectively) repeated three handgrip-exercise protocol that consisted of 1 min IH exercise at 15, 30, or 45% of maximum voluntary contractions (MVC) followed by 2 min post-exercise forearm occlusion. Local sweat rates on forehead, chest, forearm, thigh, and palm were continuously measured (ventilated-capsule method). Forehead sweat rate (SR) in prepubertal children during IH exercise at 45%MVC was significantly lower than that of young adults (0.26±0.22 and 0.08±0.15 mg/cm2/min for young adults and children, respectively, P<0.05) but not of the elderly at any exercise intensities. SR on chest (0.22±0.22 and -0.01±0.05 mg/cm2/min for young adults and children, respectively), forearm (0.14±0.12 and 0.03±0.04 mg/cm2/min), and thigh (0.13±0.10 and 0.02±0.03 mg/cm2/min) during post-exercise occlusion at 45%MVC was significantly lower in children than young adults (P<0.05). Elderly showed significantly lower SR on forearm (0.04±0.04 and 0.01±0.02 mg/cm2/min for young adults and elderly, respectively) and thigh (0.07±0.07 and 0.01±0.03 mg/cm2/min) at 15%MVC and on thigh at 45%MVC (0.13±0.10 and 0.04±0.04 mg/cm2/min) during post-exercise occlusion compared with young adults (P<0.05). These results suggest that sweating responses to IH exercise and muscle metaboreflex were underdeveloped in prepubertal children and then aging attenuates the response to muscle metaboreflex that were not consistent across the body.

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β1-adrenoceptor autoantibodies increase the susceptibility of ventricular arrhythmias involving abnormal repolarization in guinea pigs

High titers of autoantibodies against the second extracellular loop of β1-adrenergic receptors (β1-AA) can be detected in the sera from patients with ventricular arrhythmias, but a causal relationship between β1-AAs and ventricular arrhythmias has not been established. In this work, electrocardiograms of guinea pigs and isolated guinea pig hearts were recorded. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were evoked by programmed electrical stimulation of the left ventricular epicardium of isolated guinea pig hearts. Monophasic action potential and effective refractory period (ERP) of the left ventricle were recorded in the paced isolated guinea pig hearts. What's more, to increase the specificity, monoclonal autoantibodies against the second extracellular loop of β1-adrenergic receptor (β1-AR mAb) had been used in all experiments. The results showed that β1-AR mAbs induced premature ventricular contractions (PVC) in guinea pigs and isolated guinea pig hearts. In addition, β1-AR mAbs decreased the threshold of VT/VF and prolonged the VT/VF duration. Furthermore, β1-AR mAbs shortened corrected QT interval (QTc) and ERP, and prolonged late-phase repolarization of the monophasic action potential (MAPD90-30). These changes in electrophysiological parameters might be attributed, at least in part, to the arrhythmogenicity of β1-AR mAbs.

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Response to Letter from Tremblay & King: NIRS: Can it measure conduit artery endothelial function?

We thank Tremblay and King for their interest in our publication (McLay et al., 2016a), which has since been followed up with studies by McLay et al. (McLay et al., 2016c, 2016b). In these studies, it is suggested that the near-infrared spectroscopy (NIRS)-derived measure of tissue oxygen saturation (StO2), specifically the reperfusion rate (Slope 2) following a brief period of ischemia, can be easily applied as a reliable, non-invasive measure of vascular reactivity (McLay et al., 2016a, 2016c, 2016b). As Tremblay and King mentioned, the StO2 reperfusion rate, being measured distal to the site of occlusion, provides insight on microvascular reperfusion and it was an error in our wording that wrongfully implied that the NIRS measure of Slope 2 could be used as a surrogate for conduit artery endothelial-dependent vasodilation. We appreciate this opportunity to clarify the interpretation of the present study to avoid further confusion on this topic.

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Mathematical relationships and their consequences between rat pulse waveform parameters and blood pressure during decreasing NO bioavailability

Information obtained from arterial pulse waveform (APW) is useful for characterization of cardiovascular system in particular (patho)physiological conditions. Our goal was to find out, if the relationship between rat APW parameters could be described by simple mathematical functions and find mathematical parameters for conditions of hypertension resulted from decreased NO bioavailability. Therefore, we explored details of 14 left carotid APW parameters of anesthetized male Wistar rats and mathematically characterized their relationship to systolic and diastolic blood pressure (BP) in the condition of gradual decrease of NO bioavailability after administration of L-NAME. The right jugular vein of anesthetized Wistar rats was cannulated for L-NAME administration. The left carotid artery was cannulated to detect arterial pulse waveform at high resolution. Here we show the time-dependent parallel changes of 14 APW parameters before and after i.v. administration of L-NAME and present mathematical functions that approximate the relationships of 12 APW parameters to systolic and diastolic BP. Some APW parameters had minor (e.g. heart rate) or biphasic (e.g. relative level of dP/dtmin) dependence on BP, but all relationships, within particular range of BP, could be approximated by known regression functions, as linear line (e.g. pulse BP), exponential decay (e.g. relative level of dP/dtmax), exponential growth (systolic area), exponential rise to maximum (relative augmentation index) or sigmoid function (e.g. increase of relative level dP/dtmin). The mathematical functions may assign APW parameters to decreased NO bioavailability. This may have predictive or diagnostic value.

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Consequences of Maternal omega-3 polyunsaturated fatty acid supplementation on respiratory function in rat pups

Abstract

Most preterm infants present respiratory instabilities and apneas owing to incomplete development of the neural circuits that control breathing. Because omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit brain development, we hypothesized that n-3 PUFA supplementation (via maternal diet) improves respiratory function in rat pups. Pups received n-3 PUFA supplementation from an enriched diet (13 g kg−1 of n-3 PUFA) administered to the mother from birth until experiments were performed (postnatal days 10–11). Controls received a standard diet (0.3 g kg−1 of n-3 PUFA). Breathing was measured in intact pups at rest and during hypoxia (FiO2 = 0.12; 20 min) using whole body plethysmography. The duration of apneas induced by stimulating the laryngeal chemoreflex (LCR) was measured under anaesthesia. Lung morphology was compared between groups. Maternal n-3 PUFA supplementation effectively raised n-3 PUFA levels above control levels both in the blood and brainstem of pups. In intact, resting pups, n-3 PUFA increased the frequency and duration of apneas, especially in females. During hypoxia, n-3 PUFA supplemented pups hyperventilated 23% more than controls; their anapyrexic response was 1 °C less than controls. In anaesthetized pups, n-3 PUFA shortened the duration of LCR-induced apneas by 32%. The relative pulmonary surface area of n-3 PUFA supplemented pups was 12% higher than controls. While n-3 PUFA supplementation augments apneas, there is no clear evidence of deleterious consequences on these pups. Based on the improved lung architecture and responses to respiratory challenges, this neonatal treatment seems beneficial to the offspring. However, further experiments are necessary to establish its overall safety.

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All-optical functional synaptic connectivity mapping in acute brain slices using CaMPARI

The calcium-modulated photoactivatable ratiometric integrator CaMPARI (Fosque et al., 2015) facilitates the study of neural circuits by permanently marking cells active during user-specified temporal windows. Permanent marking enables measurement of signals from large swathes of tissue and easy correlation of activity with other structural or functional labels. One potential application of CaMPARI is labeling neurons postsynaptic to specific populations targeted for optogenetic stimulation, giving rise to all-optical functional connectivity mapping. Here, we characterized the response of CaMPARI to several common types of neuronal calcium signals in mouse acute cortical brain slices. Our experiments show that CaMPARI is effectively converted by both action potentials and sub-threshold synaptic inputs, and that conversion level is correlated to synaptic strength. Importantly, we found that conversion rate can be tuned: it is linearly related to light intensity. At low photoconversion light levels CaMPARI offers a wide dynamic range due to slower conversion rate; at high light levels conversion is more rapid and more sensitive to activity. Finally, we employed CaMPARI and optogenetics for functional circuit mapping in ex vivo acute brain slices, which preserve in vivo-like connectivity of axon terminals. With a single light source, we stimulated channelrhodopsin-2-expressing long-range posteromedial (POm) thalamic axon terminals in cortex and induced CaMPARI conversion in recipient cortical neurons. We found that POm stimulation triggers robust photoconversion of layer 5 cortical neurons and weaker conversion of layer 2/3 neurons. Thus, CaMPARI enables network-wide, tunable, all-optical functional circuit mapping that captures supra- and sub-threshold depolarization.

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A Time-Out Checklist for Pediatric Regional Anesthetics.

Background and Objectives: Although pediatric regional anesthesia has a demonstrated record of safety, adverse events, especially those related to block performance issues, still may occur. To reduce the frequency of those events, we developed a Regional Anesthesia Time-Out Checklist using expert opinion and the Delphi method. Methods: A content development and review was performed by the authors and the Society for Pediatric Anesthesia Quality and Safety Committee. The expert panel was composed of 12 pediatric anesthesiologists, who achieved consensus after 2 rounds of a modified Delphi method. Finally, an author who is an expert in checklist design (B.B.) provided guidance on the formatting and layout of the checklist items to ensure clarity and ease of use. The resulting checklist was trialed in a small pilot study to solicit feedback in a real-life setting. Results: Sixteen items were included in the checklist sent to the expert panel for the first round of Delphi. Items that had an average rating of 3 or more, with fewer than 3 negative comments, were retained (n = 15). Feedback led to combining several items and dividing the checklist into 2 sections based on the following temporal implementation criteria: "preoperatively" or "immediately before procedure." All remaining 12 checklist items received a positive response from more than 50% of expert panel members and therefore were retained after the second and final round of Delphi. No significant alterations were suggested in the pilot trial. Conclusions: The Delphi method and human factors principles enabled the creation of a Regional Anesthesia Time-Out Checklist based on published and experiential knowledge of adverse events. Usability of the checklist was supported through the results of a pilot study. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Anesthetic and Obstetrical Factors Associated With the Effectiveness of Epidural Analgesia for Labor Pain Relief: An Observational Population-Based Study.

Background and Objectives: The effectiveness of labor epidural analgesia is difficult to explore, as it includes the maternal satisfaction with analgesia as well as the overall childbirth experience. In this population-based study, we sought to identify factors associated with the effectiveness of epidural analgesia for labor pain relief. Methods: We performed a secondary analysis of the 2010 French National Perinatal Survey, a cross-sectional study of a representative sample of births in France. All participants who gave birth with an epidural analgesia were included. Effectiveness of epidural analgesia was assessed 2 to 3 days after delivery and intended to include analgesic efficacy and maternal satisfaction together. The factors analyzed were anesthetic management and maternal, obstetrical, and organizational characteristics, using a logistic regression with random effects model. Results: Among the 9337 women who gave birth with an epidural analgesia and were included, 8377 (89.3%; 95% confidence interval [CI] = 88.7-89.9) considered their epidural to be very or fairly effective. In the multivariate analysis, effectiveness was significantly associated with the use of patient-controlled epidural analgesia (adjusted odds ratio [aOR] = 1.2 [1.0-1.5]; P = 0.02) and delivery in private maternity facilities (aOR = 1.3 [1.1-1.6]); it was significantly less effective in obese women (aOR = 0.6 [0.5-0.8]) and multiparous women not receiving oxytocin during labor (aOR = 0.4 [0.4-0.6]) as compared with nonobese and nulliparous women with oxytocin, respectively. Conclusions: At the population level, most women found epidural analgesia effective for labor pain relief, but specific attention should be paid to obese parturients and multiparous women not receiving oxytocin. High epidural effectiveness with patient-controlled analgesia should promote an increased use of this method. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Prospective, Double-Blind, Randomized Study to Evaluate Single-Injection Adductor Canal Nerve Block Versus Femoral Nerve Block: Postoperative Functional Outcomes After Total Knee Arthroplasty.

Background and Objectives: Despite multiple clinical trials comparing the adductor canal block (ACB) with femoral nerve block (FNB) for total knee arthroplasty, none looked at the aforementioned nerve blocks from early functional results to up to 6 months after surgery. Methods: For this prospective, double-blind, randomized, single-center trial, we enrolled 98 patients set to undergo total knee arthroplasty. The patients were randomized, with 93 patients included in the intention-to-treat analysis. Subjects received injections of both ACB and an FNB, with 1 containing 30 mL of saline (placebo) and the other 30 mL of local anesthetic (treatment) depending on randomization. Adductor canal block and FNB were compared using percentage of baseline maximum voluntary isovolumetric contraction (MVIC) of the quadriceps muscle retained at 6 (primary endpoint), 24, and 48 hours and 6 months postoperatively. Secondary endpoints also included Timed Up and Go, range of motion, 6-minute walking test, pain score, and postoperative pain medication use. Results: Percent MVIC retained was significantly higher in ACB patients at 6 (P

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Clinical Efficacy of an Ultrasound-Guided Greater Occipital Nerve Block at the Level of C2.

Background and Objectives: The purpose of this prospective open-label study was to investigate the analgesic effects of an ultrasound-guided greater occipital nerve (GON) block at the level of C2, as the nerve courses superficially to the obliquus capitis inferior muscle. Methods: Patients with a diagnosis of occipital neuralgia or cervicogenic headache were recruited for the study. Ultrasound-guided GON blocks at the level of C2 were performed by experienced clinicians according to a standardized protocol. Numeric rating scale pain scores were recorded preinjection and at 30 minutes, 2 weeks, and 4 weeks after injection. Results: A total of 14 injections were performed with a mean procedure time of 3.75 minutes. Anesthesia in the GON distribution was achieved for 86% of patients at 30 minutes postinjection. Compared with baseline, numeric rating scale scores decreased by a mean of 3.78 at 30 minutes (P

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A Cadaveric Study Evaluating the Feasibility of an Ultrasound-Guided Diagnostic Block and Radiofrequency Ablation Technique for Sacroiliac Joint Pain.

Background and Objectives: Ultrasound (US)-guided diagnostic block/radiofrequency ablation (RFA) along the lateral sacral crest (LSC) has been proposed for managing sacroiliac joint (SIJ) pain. We sought to investigate (1) ease of visualization of bony landmarks using US; (2) consistency of US-guided needle placement along the LSC; and (3) percentage of the posterior sacral network (PSN) innervating the SIJ complex that would be captured if an RFA strip lesion were created between the needles. Methods: In 10 cadaveric specimens, 3 needles were placed bilaterally along the LSC from the first to third transverse sacral tubercles (TSTs) using US guidance. The PSN, SIJ, and needles were exposed, digitized, and modeled 3-dimensionally. Ease of visualization of bony landmarks, frequency of needle placement along the LSC, and percentage of the PSN that would be captured if an RFA strip lesion were created between the needles were determined. Results: The LSC, TST2, TST3, and first to third posterior sacral foramina were easily visualized using US; TST1 was somewhat obscured by the iliac crest in some specimens. Needles were placed along the LSC in 18 of 20 specimens; in the first 2 of 20 specimens, needle 1 was placed at the L5/S1 facet joint. On average, 93% (95% confidence interval, 87%-98%) of the PSN would be captured if an RFA strip lesion were created between the needles. Conclusions: The findings suggest that US-guided needle placement along the LSC is consistent and could capture most or all of the PSN. A clinical study evaluating the outcomes of this technique is in progress. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Anti-proliferative effects of paeonol on human prostate cancer cell lines DU145 and PC-3

Abstract

Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by MTT, and the apoptosis was detected by the flow cytometry. Expression of Bcl-2, Bax, Akt, and mTOR were tested by western blotting assay. DU145 and PC-3 showed remarkable sensitivity to Pae, and exposure to Pae induced dose-and time-dependent growth inhibitory responses. Moreover, treatment of Pae promoted apoptosis and enhanced activities of caspase-3, caspase-8, and caspase-9 in DU145. Further work demonstrated Pae reduced expression of Bcl-2 and increased expression of Bax in DU145. Interestingly, we observed that Pae significantly decreased phosphorylated status of Akt and mTOR, and inhibitory effects of Pae and PI3K/Akt inhibitor on DU145 proliferation were synergistic. Finally, we confirmed that oral administration of Pae to the DU145 tumor-bearing mice significantly lowered tumor cell proliferation and led to tumor regression. Pae possesses inhibitory effects on prostate cancer cell growth both in vitro and in vivo, and the anti-proliferative effect may be closely related to its activation of extrinsic and intrinsic apoptotic pathway and inhibition of the PI3K/Akt pathway.



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