Application Of Negative Pressure Research Articles

Non-interventional monitoring of expiratory flow limitation during experimental mechanical ventilation.

BackgroundExpiratory flow limitation (EFL) is common among patients in the intensive care unit under mechanical ventilation (MV) and may have significant clinical consequences. In the present study, we examine the possibility of non-interventional detection of EFL during experimental MV.MethodsEight artificially ventilated New Zealand rabbits were included in the experiments. EFL was induced during MV by application of negative expiratory pressure (−5, −8 and −10 hPa) and detected by the negative expiratory pressure technique. Airway pressure (Paw) and gas flow (V′) were digitally recorded and processed off-line for the evaluation of respiratory mechanics. The method is based on the computation and monitoring of instantaneous respiratory resistance Rrs(t). The resistive pressure (Paw,res(t)) is calculated by subtracting from Paw its elastic component and the end-expiratory pressure, as assessed by linear regression. Then, Rrs(t) is computed as the instant ratio Paw,res(t)/V′(t).ResultsTwo completely different patterns of expiratory Rrs(t) separate the cases with EFL from those without EFL. Small and random fluctuations are noticed when EFL is absent, whereas the onset of EFL is accompanied by an abrupt and continuous rise in Rrs(t), towards the end of expiration. Thus, EFL is not only detected but may also be quantified from the volume still to be expired at the time EFL occurs.ConclusionThe proposed technique is a simple, accurate and non-interventional tool for EFL monitoring during MV.

Short-Term Steady-State Pattern Electroretinography Changes Using a Multi-Pressure Dial in Ocular Hypertensive, Glaucoma Suspect, and Mild Open-Angle Glaucoma Patients: A Randomized, Controlled, Prospective, Pilot Study.

IntroductionThis study evaluates the effects of the multi-pressure dial (MPD) on steady-state pattern electroretinography (ss-pERG) parameters. The study is a randomized, controlled, prospective, pilot trial in a private practice setting with ocular hypertensive (OHT), glaucoma suspect, and open-angle glaucoma (OAG) subjects.MethodsThis study included nine patients (64 ± 9.0 years, nine female) with OHT, glaucoma suspect, or mild OAG. One eye of each subject was randomized to receive negative periocular pressure, while the contralateral eye served as the intrasubject control through the goggle without negative pressure. The Diopsys High Contrast Sensitivity ss-pERG protocol was conducted on both eyes of each subject while wearing the MPD device. Application of negative periocular pressure was set at 50% of baseline intraocular pressure for each study eye.ResultsFollowing 2 h of negative periocular pressure application, the difference in MagnitudeD (MagD) from baseline for eyes randomized to receive negative periocular pressure (+ 0.17 versus − 0.26) was statistically significant (p = 0.023). Over the same period, the change in MagD/Magnitude (MagD/Mag ratio) from baseline for eyes randomized to receive negative periocular pressure was also higher (+ 0.14 versus − 0.16), compared to the control eyes, approached significance (p = 0.059).ConclusionsFollowing 2 h of MPD wear, the measured MagD and MagD/Mag ratio improved compared to control, suggesting that negative periocular pressure application to the anterior globe can lead to short-term improvement in one measure of retinal ganglion cell function.

<p>Overnight Safety Evaluation of a Multi-Pressure Dial in Eyes with Glaucoma: Prospective, Open-Label, Randomized Study</p>

PurposeTo investigate the safety and tolerability of the multi-pressure dial (MPD) worn overnight for seven consecutive days.DesignProspective, open-label, randomized, single-site study.SubjectsTwenty eyes of 10 subjects with open-angle glaucoma were fitted with an MPD and randomized to negative pressure application of −10 mmHg in one eye (study eye) worn overnight for 7 consecutive days.MethodsSafety measures included best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline during and after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were completed daily by the subjects during the 7-day study period and immediately following the study period.ResultsPrior to the 7-day testing period, application of 10 mmHg negative pressure reduced mean IOP from 18.2 ± 3.8 mmHg to 14.0 ± 2.1 mmHg (p<0.01), a 22% reduction. After 7 days of consecutive nightly wear, repeat IOP measurements with the application of negative pressure showed a decrease in mean IOP from 16.9 ± 4.3 mmHg to 13.5 ± 3.7 mmHg. The observed IOP reduction was in addition to the subjects’ current treatment regimen. There were no statistically significant changes in IOP, BCVA from baseline following the 7-day period of nightly wear with the application of negative pressure. The patient-reported outcomes were favorable.ConclusionThe MPD can safely and comfortably be worn overnight. The decrease in IOP of >20% in addition to current therapy is both clinically and statistically significant. The MPD shows promise as a potential new treatment option for nocturnal IOP control.

Mechanical behavior of metallic glasses with pressure-promoted thermal rejuvenation

The pressure-promoted thermal rejuvenation is a promising approach for improving the macroscopic plasticity of metallic glasses (MGs). Here, molecular dynamics simulations have been performed to investigate the atomic structure and mechanical behavior of the rejuvenated MGs with pressure-promoted thermal processing. The effects of annealing temperatures and pressures are investigated, with results suggesting that the pressure has a significant influence on the deformation and failure mechanism of the rejuvenated MGs. The MGs can be rejuvenated either by the application of negative pressures with the low annealing temperature, or by the application of positive pressures with the high annealing temperature. Accompanied by the rejuvenation, a transition in failure mode from localized shear banding to homogeneous plastic deformation occurs due to the higher-energy glassy state induced by the thermal-pressure loading process. The present study provides important insights into the atomic-level structures of the rejuvenated MGs, as well as useful guidelines for the design of strong and high plastic MGs.

Zastosowanie terapii podciśnieniowej w leczeniu ran

Terapia podciśnieniowa to metoda, która opiera się na wykorzystaniu podciśnienia i jest szeroko stosowana w leczeniu ran o różnej etiologii. Mechanizm terapii podciśnieniowej bazuje na kontrolowanym wytwarzaniu podciśnienia bezpośrednio w łożysku rany. Leczenie podciśnieniem przyspiesza gojenie się rany, skraca czas hospitalizacji pacjentów oraz wpływa na procesy regeneracyjne w uszkodzonych tkankach. Dzięki użyciu opatrunku podciśnieniowego dochodzi do zmniejszenia obrzęku, co jest spowodowane wchłanianiem płynu tkankowego, poprawy krążenia w łożysku rany, utworzenia ziarniny, zmniejszenia obszaru tkanek martwiczych oraz zahamowania rozwoju bakterii. Powoduje to większą skuteczność i szybkość procesów naprawczych w obrębie rany. Leczenie podciśnieniem wykorzystywane jest w terapii: owrzodzeń, rozejść ran, oparzeń, odleżyn, ale także w przypadku amputacji, przeszczepów skóry, ran pourazowych, ostrych, przewlekłych i innych. Przeciwwskazaniami do wdrożenia terapii podciśnieniowej są np. niewielkie przetoki, nowotwory w miejscu rany, nieleczone zapalenia kości oraz widoczne naczynia krwionośne lub organy. Metoda ta jest nowoczesną alternatywą dla dotychczasowych sposobów leczenia i pielęgnacji ran, a także może służyć jako ich uzupełnienie. Masywne bądź mniejsze rany leczone z wykorzystaniem terapii podciśnieniowej goją się często lepiej i charakteryzują się mniejszą liczbą defektów estetycznych w porównaniu z czasochłonnymi i drogimi tradycyjnymi opatrunkami. Poza aparatami do podciśnienia wykorzystywanymi w szpitalnictwie novum stanowią jednorazowe urządzenia podciśnieniowe. Są to miniaturowe mechanizmy służące do leczenia podciśnieniem niewielkich ran – nie tylko w lecznictwie szpitalnym, ale również w domu. Celem pracy było przedstawienie klinicznego zastosowania terapii podciśnieniowej w leczeniu ran różnorodnego pochodzenia na podstawie analizy najnowszej literatury.

A rare case of left sided trans-mediastinal herniation of right lung, its management and review of literature

Mediastinal herniation can occur either due to traction as in the case of lung shrinkage in tuberculosis and chronic bronchostenosis or pulsion as a result of hydropneumothorax, empyema necessitans, and chronic infective etiology. We are reporting a case of left sided trans-mediastinal herniation of right lung in a patient with underlying right pulmonary tuberculosis, presenting with empyema thoracis. Empyema thoracis in pulmonary tuberculosis may either be a cause of trans-mediastinal herniation of lung or be a co-existent condition when the herniation occurs due to hydropneumothorax. Due to the presence of infection in pleural space, a prosthesis cannot be used. Due to the proximity of hernia sac to heart and major vessels, its plication is better avoided. Hence, treatment of such a case can be done by applying negative pressure for a few post-operative days till the dead space has been obliterated. Trans-mediastinal herniation of lung with underlying empyema thoracis requiring decortication can be successfully treated with the application of intermittent strong negative pressure (after completing decortication) in the pleaural cavity near mediastinum to gradually deliver the herniated lung to its normal position followed by application of negative pressure in the post op period through one of the ICDTs (intercostal drainage tubes) to avoid unnecessary post-operative complications or reherniation.

White Mountain Expedition 2019: The Impact of Sustained Hypoxia on Cerebral Blood Flow Responses and Tolerance to Simulated Hemorrhage

IntroductionTrauma‐induced hemorrhage can occur at high altitude from a variety of causes, including battlefield injuries, motor vehicle accidents, air accidents, and major falls. The hypoxic environment of high altitude can limit the ability of the cardiovascular system to compensate for blood loss injuries, due, in part, to the reduced arterial oxygen content. In humans, the effect of sustained hypoxia on tolerance to hemorrhage and the cardiovascular and cerebrovascular responses to this stress are unknown. Based on the known compensatory increases in cerebral blood flow that occur with exposure to hypoxia, we hypothesized that tolerance to simulated hemorrhage (via application of lower body negative pressure, LBNP) at high altitude would be similar compared to low altitude due to increased cerebral blood flow and oxygen delivery, and the subsequent preservation of cerebral tissue oxygenation.MethodsHealthy human subjects (N=8; 4F, 4M) participated in LBNP protocols to presyncope at low altitude (1045 m, Calgary, Canada) and at high altitude (3800 m, White Mountain, California) following 4–5 days of acclimatization. LBNP chamber pressure was initially reduced to −60 mmHg for 10‐min followed by decreases every 5‐min to −70, −80, −90 and −100 mmHg, until the onset of presyncopal symptoms. Arterial pressure, heart rate, internal carotid artery blood flow, and cerebral oxygen saturation were measured continuously. Stroke volume was derived from the arterial pressure waveform, and systemic vascular resistance was calculated from cardiac output and mean arterial pressure. Time to presyncope and cardiovascular responses were compared between the low and high altitude conditions.ResultsTime to presyncope was similar between conditions (low altitude: 1276 ± 108 s vs. high altitude: 1208± 108 s; P=0.58). Similar responses to LBNP were observed between low and high altitudes in mean arterial pressure (low altitude: −16±2 % vs. high altitude: −16±2 %; P=0.85), stroke volume (low altitude: −57±5 % vs. high altitude: −60±5 %; P=0.39), systemic vascular resistance (low altitude: +23±9 % vs. high altitude: +38±12 %; P=0.21), and heart rate (low altitude: +69±12 % vs. high altitude: +65±8 %; P=0.71). Internal carotid artery blood flow was higher at high altitude vs. low altitude (condition effect, P=0.01), and decreased with LBNP under both conditions (P≤0.005). There was no effect of high altitude on cerebral oxygen saturation at baseline and presyncope (altitude Effect, P=0.73).ConclusionThese findings suggest that the hypoxia induced by ascent to high altitude (3800 m) does not affect tolerance to simulated hemorrhage in young healthy adults, which may be due to 1) similar cardiovascular reflex responses to central hypovolemia, and/or 2) the compensatory increase in cerebral blood flow and subsequent maintenance of oxygen delivery to the tissues, resulting in the preservation of cerebral oxygen saturation.Support or Funding InformationAHA 17GRNT33671110

Impact of Endoscopic Vacuum Therapy with Low Negative Pressure for Esophageal Perforations and Postoperative Anastomotic Esophageal Leaks

Introduction: Management of esophageal anastomotic leaks (AL) and esophageal perforations (EP) remains difficult and often requires an interdisciplinary treatment modality. For primary endoscopic management, self-expanding metallic stent (SEMS) placement is often considered first-line therapy. Recently, endoscopic vacuum therapy (EVT) has emerged as an alternative or adjunct for management of these conditions. So far, data for EVT in the upper gastrointestinal-tract is restricted to single centre, non-randomized trials. No studies on optimal negative pressure application during EVT exist. The aim of our study is to describe our centre’s experience with low negative pressure (LNP) EVT for these indications over the past 5-years. Patients and Methods: Between January 2014 and December 2018, 30 patients were endoscopically treated for AL (n = 23) or EP (n = 7). All patients were primarily treated with EVT and LNP between –20 and –50 mm Hg. Additional endoscopic treatment was added when EVT failed. Procedural and peri-procedural data, as well as clinical outcomes including morbidity and mortality, were analysed. Results: Clinical successful endoscopic treatment of EP and AL was achieved in 83.3% (n = 25/30), with 73.3% success using EVT alone (n = 22/30). Mean treatment duration until leak closure was 16.1 days (range 2–58 days). Additional treatment modalities for complete leak resolution was necessary in 10% (n = 3/30), including SEMS placement and fibrin glue injection. Mean hospital stay for patients with EP was shorter with 33.7 days compared to AL with 54.4 days (p = 0.08). Estimated preoperative 10-year overall survival (Charlson comorbidity score) was 39.4% in patients with AL and 59.9% in patients with EP (p = 0.26). A mean of 5.1 EVT changes (range 1–12) was needed in EP and 3.6 changes (range 1–13) in AL to achieve complete closure, switch to other treatment modality, or reach endoscopic failure (p = 0.38). Conclusion: LNP EVT enables effective minimally – invasive endoluminal leak closure from anastomotic esophageal leaks and EP in high-morbid patients. In this study, EVT was combined with other endoscopic treatment options such as SEMS placement or fibrin glue injection in order to achieve leak or perforation closure in the vast majority of patients (83.3%). Low aspiration pressures led to slower but still sufficient clinical results.

The effects of negative periocular pressure on intraocular pressure

Glaucoma is a major cause of blindness, and IOP reduction remains the only clinically-validated therapy. In this study, we analyze a novel IOP-lowering strategy that uses a modest negative pressure (vacuum) applied locally to the periorbital region by a pair of goggles with each lens individually connected to a programmable pump. Motivated by clinical data showing an IOP reduction, we used an existing validated lumped-parameter model of the eye to understand the putative mechanism of this treatment. The model considers aqueous humor dynamics, episcleral venous pressure, and changes in ocular blood volume to describe how IOP changes with time in response to an external perturbation. We find that clinical data are qualitatively and quantitatively consistent with model predictions if we include two primary mechanisms in the model: first, negative pressure application causes a relatively rapid increase in globe volume accompanied by increased blood volume in the eye. Second, negative pressure application reduces episcleral venous pressure, causing a slower adjustment of IOP due to altered aqueous humor dynamics. These results provide testable hypotheses that hopefully will lead to a fuller experimentally-driven understanding of how negative periocular pressure influences IOP. Evaluating the long-term effects of such treatments on glaucoma patients requires further clinical study.

Re-epithelialization and immune cell behaviour in an ex vivo human skin model

A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.

&lt;p&gt;8 hrs Safety Evaluation Of A Multi-Pressure Dial In Eyes With Glaucoma: Prospective, Open-Label, Randomized Study&lt;/p&gt;

PurposeTo investigate the safety and tolerability of the multi-pressure dial with a continuous 8-hr duration in subjects with open-angle glaucoma.DesignProspective, controlled open-label, randomized, single site study.SubjectsTwenty eyes of 10 subjects with open-angle glaucoma were fitted with a multi-pressure dial and randomized to negative pressure application of −10 mmHg in one eye for 8 (continuous) hours and ambient atmospheric pressure in the contralateral eye.MethodsMain safety outcome measures include best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were administered both hourly during the 8-hr study period and immediately following the study period.ResultsThere were no statistically significant changes in IOP, BCVA or TBUT immediately following the 8-hr study period or at the 1-week follow-up visit. Patient-reported tolerability was favorable with a mean response of 1.8 ± 0.4 (scale → 1=best, 10 = worst). Subjects also reported positive interest in the MPD as a glaucoma therapy with a mean response of 1.8 ± 0.5 (scale → 1=best, 10 = worst). One adverse event was reported (headache) and resolved at conclusion of the Day 0 visit.ConclusionThe MPD demonstrated favorable safety with key parameters remaining stable after an 8-hr wear with negative pressure. Negative pressure application through the MPD was well tolerated by subjects enrolled in the study. The favorable findings demonstrate the safety of sustained delivery of negative pressure over a continuous, uninterrupted 8-hr duration.

647 Investigating re-epithelialization in a novel ex vivo human skin model

Although numerous wound healing models have been established, a model to study re-epithelialization in vitro, without disrupting the underlying dermal compartment, is lacking. Therefore, we established a new standardized human ex vivo model based on application of negative pressure, inducing blistering and consequently dermal epidermal separation. Effects of this treatment for epidermal regeneration and immune cells were investigated. Immunostaining revealed type IV collagen expression on the remaining dermal compartment, indicating that the basement membrane and thus the underlying dermis remained intact after removal of the blister roof epidermis. Keratinocytes were absent in the wounded area as evidenced by a lack of K14 staining. Four to six days after removal of the epidermis and culture, the wound was completely covered again with one to three-cell thick K14+ keratinocyte layers. Keratinocytes (∼20%) covering the initial wound bed expressed the endogenous cell proliferation marker Ki67, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing several epidermal differentiation markers (e.g., K10, filaggrin, DSG-1, CDSN). While application of negative pressure did not affect the morphology, phenotype and density of Langerhans cells, we observed more T cells in the blister roof epidermis as compared to normal epidermis. Additionally, we identified several populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating an influx upon pressure. Whether and how this contributes to the wound healing process is currently under investigation. This model recapitulates the main features of epithelial wound regeneration, and thus can be applied for testing wound healing therapies and investigating the underlying mechanisms in the future.

Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions

Background:Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (Treg) expression under intermittent hypobaric conditions.Methods:Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of Tregs (CD4 + CD25 + Foxp3 + T cells), cytokines [tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined.Results:Splenocytes, cultured with brown and white adipocytes, exhibited comparable Treg expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of Tregs. However, a decrease in Tregs was found in the white adipocyte group. TNF-α levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions.Conclusion:Both brown and white adipocytes support Treg expression when they are cultured with splenocytes. Of note, brown adipocytes maintained Treg expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.

0559 Treatment of Obstructive Sleep Apnea with Continuous Negative External Pressure

cNEP is a novel treatment for OSA that involves external application of negative pressure over the upper airway via a silicone collar with an integral vacuum source. Previous studies indicate that cNEP reduces apnea-hypopnea index (AHI) during single night polysomnography (PSG). The current study assessed cNEP during 3 weeks of home use. This was a prospective, open label, single arm study in subjects with baseline AHI between 10 and 50/hr (>80% obstructive apneas). The primary efficacy endpoint was an AHI during an observed PSG after 3 weeks of home use (PSG2), where AHI was <15/hr and < 50% of baseline. To qualify, subjects were required to fit one of the two available cNEP collar sizes and to have a successful cNEP titration as defined by an AHI < 15 and < 50% baseline during an in lab PSG (PSG1) where response to two pressures (-25 and -30 cmw) was assessed. Results: 71 subjects (46 males) were enrolled. 23 (36.5%) were treatment naïve. Demographic characteristics included (mean ± S.D.) age 54.6 ± 11; BMI 28.3 ± 4.1; baseline AHI 27.5 ± 11.7. 59 subjects completed PSG1. 27 subjects (46%) exhibited an initial response at PSG1. 16 subjects (64%) exhibited a sustained response at PSG2. An additional 5 subjects had a reduction in AHI, which did not reach the primary endpoint. Compared to baseline, mean AHI was reduced in responders at both PSG1 (6.6 v. 26.7) and PSG2 (7.6 v. 26.7) (p<0.001). Nightly usage of cNEP averaged 4.34 hours. Most subjects and their bed partners preferred cNEP to other OSA treatments. Adverse events consisted mainly of transient local irritation at the collar site. In four subjects, AHI increased from baseline during PSG1 and changed the OSA severity classification in three. Conclusions: cNEP is a safe, effective and well-tolerated intervention during 3 weeks of home use in subjects with moderate and severe OSA. Support: Sommetrics, Inc.

Routine oro/nasopharyngeal suction versus no suction at birth.

For the current issue of the Journal, we asked Dr. Manoj Kumar to comment on and put into context the recent Cochrane Review on routine nasal suction at birth. Oro/nasopharyngeal suction is a method used to clear secretions from the oropharynx and nasopharynx through the application of negative pressure via a suction catheter or bulb syringe. Traditionally, airway oro/nasopharyngeal suction at birth has been used routinely to remove fluid rapidly from the oropharynx and nasopharynx in vigorous and nonvigorous infants at birth. Concerns relating to the reported adverse effects of oro/nasopharyngeal suctioning led to a practice review and routine oro/nasopharyngeal suctioning is no longer recommended for vigorous infants. However, it is important to know whether there is any clear benefit or harm for infants whose oro/nasopharyngeal airway is suctioned compared with infants who are not suctioned. The objective of this study was to evaluate the effect of routine oropharyngeal/nasopharyngeal suction compared with no suction on mortality and morbidity in newly born infants.

Short-Term Safety Evaluation of a Multi-Pressure Dial: A Prospective, Open-label, Non-randomized Study.

IntroductionProspective, open-label, non-randomized, single site study to assess the safety and tolerability of a multi-pressure dial.Methods30 healthy subjects received application of negative pressure (–15 mmHg) in one eye for 30 minutes and ambient atmospheric pressure in the contralateral eye. To evaluate safety, the primary outcome measures included best corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline, slit-lamp and dilated fundus examination findings, and rate of adverse events. Exploratory analyses included in this study also evaluated changes from baseline measurement in tear break-up time (TBUT) and RNFL thickness measured by OCT. In addition to baseline screening, subjects underwent testing and negative pressure application on day 0 and returned 1 week after the initial visit for clinical testing. The follow-up visit did not include use of the multi-pressure dial (MPD) but repeated baseline testing and evaluated for adverse events.ResultsNo adverse events were reported in the study. After short-term wear of the MPD on day 0, there was a minimal but statistically significant increase of half a line (LogMAR) in BCDVA for study eyes; this increase was not present at 1 week. There were no observed changes in cup-disk ratio and TBUT 1 week after the initial testing. There was a statistically significant pressure reduction in both study and fellow eyes at 1 week following the study, but clinical significance has yet to be determined.ConclusionThe MPD, which consists of a pair of goggles connected to a handheld, programmable pump, was well tolerated by subjects enrolled in the study. Key safety parameters remained stable after short-term exposure. The favorable safety results of this study support the safety profile of the MPD and promote further investigation of the device as a potential treatment of glaucoma.FundingEquinox Ophthalmic, Inc. (Newport Beach, CA).

Effect of vacuum-release teat versus standard teat use on feeding milestones and breastfeeding outcomes in very preterm infants: A randomized controlled trial.

BackgroundBreast milk is important to infant health, yet shorter breastfeeding duration is reported for preterm infants. Both breast and bottle feeds are given in the neonatal unit, with full oral feeding often the last milestone to be achieved prior to discharge home. Unlike standard bottle teats, a vacuum release teat requires the application of negative intra-oral pressure to release milk, and so may facilitate breastfeeding in preterm infants. The objective of this study was to determine the effect of vacuum release teat use on timing of achievement of the first full oral feed and on first completion of 24 h full oral feeds. Feeding method at discharge home, 2 weeks, 6 weeks and 12 weeks corrected gestational age were also examined.MethodsA randomized controlled trial was completed with mothers of preterm infants born 24–33 weeks gestation in the neonatal unit of a tertiary women’s hospital. Infants were randomized to one of two parallel groups using a vacuum release teat or standard teat for oral feeds when the mother was not available to breastfeed. Test weights were completed for all oral feeds. It was not possible to blind participants, care givers and outcome assessors to group assignment due to the nature of the study.ResultsThe groups did not differ with regard to timing of achievement of first full oral feed or 24 h of full oral feeds. Significantly more infants in the vacuum release teat group were exclusively fed breast milk at discharge from hospital and breastfed at 3 months corrected gestational age.ConclusionsUse of a vacuum release teat when the mother is not available to breastfeed may promote preterm breastfeeding skills, resulting in higher rates of exclusivity and longer breastfeeding duration.Trial registrationThe trial is registered with the Australian New Zealand Clinical Trials Registry ACTRN12615000245594.

Coagulation changes induced by lower-body negative pressure in men and women.

We investigated whether lower-body negative pressure (LBNP) application leads to coagulation activation in whole blood (WB) samples in healthy men and women. Twenty-four women and 21 men, all healthy young participants, with no histories of thrombotic disorders and not on medications, were included. LBNP was commenced at -10 mmHg and increased by -10 mmHg every 5 min until a maximum of -40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both men and women using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. LBNP led to coagulation activation determined in both plasma and WB samples. At baseline, women were hypercoagulable compared with men, as evidenced by their shorter "lag times" and higher thrombin peaks and by shorter "coagulation times" and "clot formation times." Moreover, men were more susceptible to LBNP, as reflected in their elevated factor VIII levels and decreased lag times following LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. Women appear to be relatively hypercoagulable compared with men, but men are more susceptible to coagulation changes during LBNP. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis. NEW & NOTEWORTHY LBNP led to coagulation activation determined in both plasma and whole blood samples. At baseline, women were hypercoagulable compared with men. Men were, however, more susceptible to coagulation changes during LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis.

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults.

We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.

Rapid and Sensitive Determination of Branched-Chain Amino Acids in Human Plasma by Capillary Electrophoresis with Contactless Conductivity Detection for Physiological Studies.

Capillary electrophoresis (CE) with contactless conductivity detection (C4D) represents a strong tool for determining amino acids in clinical samples. This chapter provides detailed instructions for CE/C4D determination of the branched-chain amino acids (BCAAs) valine, isoleucine, and leucine in human plasma, which can be readily employed in physiological studies. Baseline separation of all the BCAAs is achieved on a short separation length equal to 18cm in optimized background electrolyte consisting of 3.2M acetic acid dissolved in 20% v/v methanol with addition of 1.0% v/v INST-coating solution. The analysis time does not exceed 3min and the limit of detection is 0.4μM for all BCAAs. The pretreatment of human plasma is very simple and is based on fourfold plasma dilution by acetonitrile and subsequent filtration. Only 50μL of plasma is used for the analysis. The high sensitivity of the CE/C4D method is achieved by injecting a large volume of sample, combined with application of negative pressure to flush the acetonitrile zone out of the capillary.