New Trends in Biosurfactants: From Renewable Origin to Green Enhanced Oil Recovery Applications.

Enhanced oil recovery (EOR) processes are technologies used in the oil and gas industry to maximize the extraction of residual oil from reservoirs after primary and secondary recovery methods have been carried out. The injection into the reservoir of surface-active substances capable of reducing the surface tension between oil and the rock surface should favor its extraction with significant economic repercussions. However, the most commonly used surfactants in EOR are derived from petroleum, and their use can have negative environmental impacts, such as toxicity and persistence in the environment. Biosurfactants on the other hand, are derived from renewable resources and are biodegradable, making them potentially more sustainable and environmentally friendly. The present review intends to offer an updated overview of the most significant results available in scientific literature on the potential application of biosurfactants in the context of EOR processes. Aspects such as production strategies, techniques for characterizing the mechanisms of action and the pros and cons of the application of biosurfactants as a principal method for EOR will be illustrated and discussed in detail. Optimized concepts such as the HLD in biosurfactant choice and design for EOR are also discussed. The scientific findings that are illustrated and reviewed in this paper show why general emphasis needs to be placed on the development and adoption of biosurfactants in EOR as a substantial contribution to a more sustainable and environmentally friendly oil and gas industry.

Nurse-Led Telephonic Palliative Care: A Case-Based Series of a Novel Model of Palliative Care Delivery.

Americans near the end of life experience high rates of nonbeneficial, burdensome, and preventable hospital-based care. If patients' goals of care are unknown or unclear, they have higher rates of hospitalization at the end of life. The demand for palliative care has grown exponentially because of its impact on quality of life, symptom burden, and resource use, requiring the development of new palliative care models. Nurses' holistic outlook and patient-centered focus make them ideal to deliver telephonic palliative care. This article discusses 4 cases delivered by a nurse-led telephonic palliative care program, a part of the Emergency Medicine Palliative Care Access project, which is a randomized controlled trial comparing outpatient palliative care with nurse-led telephonic case management after an emergency department visit. Telephonic nurses discuss patients' goals, fears, hopes, and concerns regarding their illness and its trajectory that inform decisions for future interventions and treatments. In addition, they share this information with the patients' surrogate decision-makers and clinicians to facilitate care coordination and symptom management. For seriously ill patients, nurses' abilities and expertise, as well as the difficulties of providing care through in-person models of palliative care delivery, make a nurse-led telephonic model an optimal option.

Telemedicine and Telehealth in Nursing Homes: An Integrative Review.

OBJECTIVES: Telemedicine and telehealth are increasingly used in nursing homes (NHs). Their use was accelerated further by the COVID-19 pandemic, but their impact on patients and outcomes has not been adequately investigated. These technologies offer promising avenues to detect clinical deterioration early, increasing clinician's ability to treat patients in place. A review of literature was executed to further explore the modalities' ability to maximize access to specialty care, modernize care models, and improve patient outcomes. DESIGN: Whittemore and Knafl's integrative review methodology was used to analyze quantitative and qualitative studies. SETTING AND PARTICIPANTS: Primary research conducted in NH settings or focused on NH residents was included. Participants included clinicians, NH residents, subacute patients, and families. METHODS: PubMed, Web of Science, CINAHL, Embase, PsycNET, and JSTOR were searched, yielding 16 studies exploring telemedicine and telehealth in NH settings between 2014 and 2020. RESULTS: Measurable impacts such as reduced emergency and hospital admissions, financial savings, reduced physical restraints, and improved vital signs were found along with process improvements, such as expedient access to specialists. Clinician, resident, and family perspectives were also discovered to be roundly positive. Studies showed wide methodologic heterogeneity and low generalizability owing to small sample sizes and incomplete study designs. CONCLUSIONS AND IMPLICATIONS: Preliminary evidence was found to support geriatrician, psychiatric, and palliative care consults through telemedicine. Financial and clinical incentives such as Medicare savings and reduced admissions to hospitals were also supported. NHs are met with increased challenges as a result of the COVID-19 pandemic, which telemedicine and telehealth may help to mitigate. Additional research is needed to explore resident and family opinions of telemedicine and telehealth use in nursing homes, as well as remote monitoring costs and workflow changes incurred with its use.

The shifting picture of HIV treatment, comorbidity and substance use among US MSM living with HIV.

OBJECTIVES: People living with HIV (PLWH) have increased risk of chronic disease and poor mental health. We aimed to explore HIV disease indicators, comorbidity, and risk behavior of recent antiretroviral therapy (ART) initiators to inform current needs of PLWH. METHODS: Men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS) who initiated ART between 2010 and 2018 (recent initiators) were compared with age-, race- and geographic location-matched men who initiated ART during 2000-2009 (early initiators). Measures of HIV disease, behavior, comorbidity and mental health were collected prospectively every 6 months using standardized forms. RESULTS: Recent initiators had higher current CD4 (median CD4 451 vs. 307 cells/µL, P < 0.0001) and nadir CD4 (451 vs. 300 cells/µL, P < 0.0001) than earlier initiators. The proportion achieving viral suppression within a year of starting ART was significantly higher in recent compared with earlier initiators (92% vs. 74%, P < 0.0001). Median [interquartile range (IQR)] time from HIV diagnosis to ART initiation was 5.4 (1.7-23.1) months in recent initiators. Comorbidity prevalence was high in recent initiators, including obesity (24%), hypertension (25%) and kidney disease (15%). Substance use continues to be common, including cigarette use (40%), daily alcohol use (88%) and marijuana use (46%). CONCLUSIONS: Improvements in getting individuals onto ART at an early stage have led to substantially higher CD4 cell counts at initiation. However, the high burden of comorbidity, substance use and poor mental health affecting MSM living with HIV in the US underscore ongoing challenges and our need to adapt and coordinate care.

Pharmacological and Nutritional Modulation of Vascular Calcification.

Vascular calcification is an independent predictor of cardiovascular disease, and therefore, inhibition or regression of this processes is of clinical importance. The standard care regarding prevention and treatment of cardiovascular disease at this moment mainly depends on drug therapy. In animal and preclinical studies, various forms of cardiovascular drug therapy seem to have a positive effect on vascular calcification. In particular, calcium channel blockers and inhibitors of the renin-angiotensin-aldosteron system slowed down arterial calcification in experimental animals. In humans, the results of trials with these drugs are far less pronounced and often contradictory. There is limited evidence that the development of new atherosclerotic lesions may be retarded in patients with coronary artery disease, but existing lesions can hardly be influenced. Although statin therapy has a proven role in the prevention and treatment of cardiovascular morbidity and mortality, it is associated with both regression and acceleration of the vascular calcification process. Recently, nutritional supplements have been recognized as a potential tool to reduce calcification. This is particularly true for vitamin K, which acts as an inhibitor of vascular calcification. In addition to vitamin K, other dietary supplements may also modulate vascular function. In this narrative review, we discuss the current state of knowledge regarding the pharmacological and nutritional possibilities to prevent the development and progression of vascular calcification.

Functional annotation of chemical libraries across diverse biological processes.

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

Sustained Reduction of Blood Pressure With Baroreceptor Activation Therapy: Results of the 6-Year Open Follow-Up.

Baroreflex activation therapy is a novel technique for treating patients with resistant hypertension. Although short-term studies have demonstrated that it lowers blood pressure, long-term results have not yet been reported. The aim of the present study is to assess the long-term efficacy and safety of baroreflex activation therapy. Long-term follow-up data were analyzed from all patients who had been included in 1 of the 3 trials that focused on treatment-resistant hypertensive patients. Altogether, 383 patients were available for analysis: 143 of these had completed 5 years of follow-up and 48 patients had completed 6 years of follow-up. In the entire cohort, office systolic blood pressure fell from 179±24 mm Hg to 144±28 mm Hg (P<0.0001), whereas office diastolic pressure dropped from 103±16 mm Hg to 85±18 mm Hg (P<0.0001). Heart rate fell from 74±15 beats per minute to 71±13 beats per minute (P<0.02). The effect of baroreflex activation therapy is greater than average in patients with signs of heart failure and less than average in patients with isolated systolic hypertension. In ≈25% of patients, it was possible to reduce the number of medications from a median of 6 to a median of 3. Temporary side effects, related to either the surgical procedure or the cardiovascular instability, do occur, but they do not require specific measures and resolve over time.After a follow-up of 6 years, baroreflex activation therapy maintains its efficacy for persistent reduction of office blood pressure in patients with resistant hypertension without major safety issues.

An exploratory propensity score matched comparison of second-generation and first-generation baroreflex activation therapy systems.

Baroreflex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open-label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 ± 28 mm Hg (mean ± standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group (P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial.

ENHANCED RADIOACTIVE CONTENT OF 'BALANCE' BRACELETS.

During a routine whole body counting measurement of a worker at the Nuclear Research Center Negev, abnormal activities of (232)Th and (238)U were measured. After a thorough investigation, it was found that the radioactivity was due to a rubber bracelet ('balance bracelet') worn by the worker during the measurement. The bracelet was counted directly by an high pure germanium gamma spectrometry system, and the specific activities determined were 10.80 ± 1.37 Bq g(-1) for (232)Th and 5.68 ± 0.88 Bq g(-1) for natural uranium. These values are obviously high compared with normally occurring radioactive material (NORM) average values. The dose rate to the wrist surface was estimated to be ∼3.9 µGy h(-1) and ∼34 mGy for a whole year. The dose rate at the centre of the wrist was estimated to be ∼2.4 µGy h(-1) and ∼21 mGy for a whole year. The present findings stresses a more general issue, as synthetic rubber and silicone products are common and widely used, but their radioactivity content is mostly uncontrolled, thus causing unjustified exposure due to enhanced NORM radioactivity levels.

Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial).

Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.

Baroreflex activation therapy lowers arterial pressure without apparent stimulation of the carotid bodies.

Carotid baroreflex activation therapy produces a sustained fall in blood pressure in patients with resistant hypertension. Because the activation electrodes are implanted at the level of the carotid sinus, it is conceivable that the nearby located carotid body chemoreceptors are stimulated as well. Physiological stimulation of the carotid chemoreceptors not only stimulates respiration but also increases sympathetic activity, which may counteract the effects of baroreflex activation. The aim of this exploratory study is to investigate whether there is concomitant carotid chemoreflex activation during baroreflex activation therapy. Fifteen participants with the Rheos system were included in this single-center study. At arrival at the clinic, the device was switched off for 2 hours while patients were at rest. Subsequently, the device was switched on at 6 electric settings of high and low frequencies and amplitudes. Respiration and blood pressure measurements were performed during all device activation settings. Multilevel statistical models were adjusted for age, sex, body mass index, antihypertensive therapeutic index, sleep apnea, coronary artery disease, systolic blood pressure, and heart rate. There was no change in end-tidal carbon dioxide, partial pressure of carbon dioxide, breath duration, and breathing frequency during any of the electric settings with the device. Nevertheless, mean arterial pressure showed a highly significant decrease during electric activation (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not stimulate respiration at several electric device activation energies, which suggests that there is no appreciable coactivation of carotid body chemoreceptors during device therapy.

Baropacing as a new option for treatment of resistant hypertension.

Electrical carotid baroreflex activation therapy is an emerging device-based treatment for patients with resistant hypertension. Its blood pressure lowering effect has been demonstrated in several animal and human studies, with prolonged effect over the long-term. The main mechanism of the blood pressure reduction during this therapy is by inhibition of the sympathetic outflow. Yet the question arises whether the inhibition of central sympathetic activity is sufficient to be the sole mechanism behind the sustained reduction in blood pressure. The major focus of this review is to elucidate the mechanisms of action that account for the effects of continuous carotid baroreflex activation on blood pressure in humans. Recent results of baroreflex activation therapy as a treatment for heart failure will also be discussed.

Bilateral or unilateral stimulation for baroreflex activation therapy.

UNLABELLED: Previous trials have shown that in patients with resistant hypertension device-based baroreflex activation therapy (BAT) can substantially reduce blood pressure. However, the fact that electrodes had to be implanted bilaterally may be a drawback for further development of the technique. In this study, we explored whether unilateral stimulation would produce comparable results as bilateral stimulation. In the Pivotal trial, treatment-resistant hypertensive patients were randomized to receive either immediate BAT or deferred BAT, that is, 6 months after implantation. We adjusted stimulation parameters individually so as to provide optimal baroreflex activation. Unilateral stimulation was applied unless bilateral stimulation resulted in a greater blood pressure reduction. When we pooled the 6-month data for the group with immediate BAT and the 12-month data for the group with deferred BAT, a total of 215 patients had been stimulated on one side only (127 at the right side and 88 at the left side), whereas 80 patients had been stimulated bilaterally. Although blood pressure and heart rate did not differ between the 2 groups at baseline, all these variables were significantly lower in the unilateral than in the bilateral group after the 6-month period. When we compared the effect of right-sided stimulation with those of either left-sided or bilateral stimulation, we found right-sided stimulation to be the most effective. We conclude that unilateral and in particular right-sided BAT has a more profound effect on blood pressure than bilateral or left-sided BAT. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00442286.

Baroreflex activation therapy for patients with drug-resistant hypertension.

Uncontrolled or resistant hypertension is still a major problem facing many physicians daily in the clinic. Several new therapies are being developed to help those patients whose blood pressure does not respond sufficiently to regular antihypertensive medication. One of these promising therapies is electrical activation of the carotid sinus baroreflex. In this overview, the authors predominantly summarize the background, efficacy and safety of this promising treatment with its latest achievements in patients with resistant hypertension. The authors also discuss certain issues that need further clarification before this therapy can be added to the common treatment guidelines of hypertension.

Renal responses to long-term carotid baroreflex activation therapy in patients with drug-resistant hypertension.

Carotid baroreflex activation has been demonstrated to provide enduring reductions in arterial blood pressure. The aim of this study was to investigate the effect of long-term therapy on renal function. A total of 322 patients were enrolled in the Rheos Pivotal Trial. Group 1 consisted of 236 patients who started baroreflex activation therapy 1 month after device implantation, whereas in the 86 patients from group 2 the device was activated 6 months later. Serum creatinine and urine albumin/creatinine ratio were collected at screening (before device activation), and at months 6 and 12. Multilevel statistical analyses were adjusted for various covariables. Serum creatinine increased from 78 to 84 µmol/L, and glomerular filtration rate decreased from 92 to 87 mL/min per 1.73 m(2) in group 1 at month 6 (P<0.05). These values did not change any further after 12 months of therapy. Patients with highest glomerular filtration rate showed the greatest decrease in glomerular filtration. Group 2 showed the same trends as group 1 even before device activation at month 6. Systolic blood pressure reduction seemed to be significantly related to the change in glomerular filtration rate in both groups. Albumin/creatinine ratio did not change in both groups during follow-up. In conclusion, baroreflex activation therapy in hypertensive patients is associated with an initial mild decrease in glomerular filtration rate, which may be considered as a normal hemodynamic response to the drop in blood pressure. Long-term treatment does not result in further decrease in renal function, indicating baroreflex activation as a safe and effective therapy.

Staining characteristics of Lonchocarpus cyanescens leaf extract on the testis of Sprague-Dawley rats.

The use of nonallergic, nontoxic, and eco-friendly natural dyes has become a matter of significant importance due to increased environmental awareness on the need to avoid hazardous synthetic dyes. This study was to determine the staining properties of the dye extract of Lonchocarpus cyanescens on histomorphology of the testis. Freshly cut leaves of L. cyanescens obtained from Akpan Ifia Inan village in Ikono local government area of Akwa Ibom state (latitude 5° 10' 12″ N; longitude 7° 48' 0″ E) were put into a plastic jar and boiling water was poured to cover the leaves. It was covered and left for an hour. The liquid was strained and potassium hydroxide was added to the dye water mixture to reach a pH of 9. A whisk was used to mix air into the liquid, and the mixuture was then allowed to sit until the blue indigo had settled to the bottom of the container. The dye was diluted with 70% ethanol to a concentration of 0.1 g/mL and was used to stain sections of testes. Its potential for use as a counterstain was also investigated. The testes sections were stained in shades of blue. The dye overshadowed the colors of haematoxylin and eosin. Preliminary phytochemical screening of L. cyanescens revealed that it contains alkaloids, saponins, flavonoids, and tannins.

Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial.

BACKGROUND: Previous trials have demonstrated clinically significant and durable reductions in arterial pressure from baroreflex activation therapy (BAT), resulting from electrical stimulation of the carotid sinus using a novel implantable device. A second-generation system for delivering BAT, the Barostim neo™ system, has been designed to deliver BAT with a simpler device and implant procedure. METHODS: BAT, delivered with the advanced system, was evaluated in a single-arm, open-label study of patients with resistant hypertension, defined as resting systolic blood pressure (SBP) ≥140 mm Hg despite treatment with ≥3 medications, including ≥1 diuretic. Stable medical therapy was required for ≥4 weeks before establishing pretreatment baseline by averaging two SBP readings taken ≥24 hours apart. RESULTS: Thirty patients enrolled from seven centers in Europe and Canada. From a baseline of 171.7 ± 20.2/99.5 ± 13.9 mm Hg, arterial pressure decreased by 26.0 ± 4.4/12.4 ± 2.5 mm Hg at 6 months. In a subset (n = 6) of patients with prior renal nerve ablation, arterial pressure decreased by 22.3 ± 9.8 mm Hg. Background medical therapy for hypertension was unchanged during follow-up. Three minor procedure-related complications occurred within 30 days of implant. All complications resolved without sequelae. CONCLUSION: BAT delivered with the second-generation system significantly lowers blood pressure in resistant hypertension with stable, intensive background medical therapy, consistent with studies of the first-generation system for electrical activation of the baroreflex, and provides a safety profile comparable to a pacemaker.

Sustained acute voltage-dependent blood pressure decrease with prolonged carotid baroreflex activation in therapy-resistant hypertension.

OBJECTIVE: Chronic carotid baroreflex stimulation (Rheos system) has been shown to effectively reduce blood pressure in patients with resistant hypertension. Upon acute stimulation blood pressure also falls as a function of voltage. the aim of this study is to evaluate whether this voltage-dependent blood pressure decrease is preserved after long-term carotid baroreflex stimulation. METHODS: Forty-five patients implanted with Rheos underwent a voltage response test (VRT) before the start of carotid baroreflex activation (1m), as well as after 4 (4m) and 13 months (13 m) of device implantation. After switching off the device for 10 min (0 V), we started the VRT by increasing voltage from 1 to 6 V, by 1-V steps every 5 min. Blood pressure and heart rate were measured at the end of every step. RESULTS: At 1m, mean blood pressure was 178/101 mmHg at 0 V and fell to 142/83 mmHg at 6 V. Heart rate fell from 75 to 65 beats/min. At 4m and 13 m mean blood pressure was significantly lower compared to 1m when VRT started at 0 V (170/96 and 161/93 mmHg, respectively). However, pattern of blood pressure decrease during VRT was comparable with this at 1m. Maximum SBP reduction during VRT did not change with long-term therapy. CONCLUSIONS: Acute voltage-dependent blood pressure and heart rate decrease with electrical baroreflex stimulation is preserved after at least 1 year of continuous activation in patients with resistant hypertension. This indicates that response adaptation and nerve fatigue are very unlikely in long-term carotid baroreflex activation.

Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial.

OBJECTIVES: We sought to determine the effect of baroreflex activation therapy (BAT) on systolic blood pressure (SBP) in patients with resistant hypertension. BACKGROUND: The Rheos Pivotal Trial evaluated BAT for resistant hypertension in a double-blind, randomized, prospective, multicenter, placebo-controlled Phase III clinical trial. METHODS: This was a double-blind randomized trial of 265 subjects with resistant hypertension implanted and subsequently randomized (2:1) 1 month after implantation. Subjects received either BAT (Group A) for the first 6 months or delayed BAT initiation following the 6-month visit (Group B). The 5 coprimary endpoints were: 1) acute SBP responder rate at 6 months; 2) sustained responder rate at 12 months; 3) procedure safety; 4) BAT safety; and 5) device safety. RESULTS: The trial showed significant benefit for the endpoints of sustained efficacy, BAT safety, and device safety. However, it did not meet the endpoints for acute responders or procedural safety. A protocol-specified ancillary analysis showed 42% (Group A) versus 24% (Group B) achieving SBP ≤140 mm Hg at 6 months (p = 0.005), with both groups achieving over 50% at 12 months, at which point Group B had received 6 months of BAT. CONCLUSIONS: A clinically meaningful measure, those achieving a SBP of ≤140 mm Hg, yielded a significant difference between the groups. The weight of the overall evidence suggests that over the long-term, BAT can safely reduce SBP in patients with resistant hypertension. Future clinical trials will address the limitations of this study and further define the therapeutic benefit of BAT.