HIV screening and linkage to care in a health department in Valencia,Spain: Lessons learned from a healthcare quality improvement project

Spain’s rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08–0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63–33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.     

Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women

Aging and menopause are associated with decreased nitric oxide bioavailability due to reduced L-arginine (L-ARG) levels contributing to endothelial dysfunction (ED). ED precedes arterial stiffness and hypertension development, a major risk factor for cardiovascular disease. This study investigated the effects of L-citrulline (L-CIT) on endothelial function, aortic stiffness, and resting brachial and aortic blood pressures (BP) in hypertensive postmenopausal women. Twenty-five postmenopausal women were randomized to 4 weeks of L-CIT (10 g) or placebo (PL). Serum L-ARG, brachial artery flow-mediated dilation (FMD), aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), and resting brachial and aortic BP were assessed at 0 and 4 weeks. L-CIT supplementation increased L-ARG levels (Δ13 ± 2 vs. Δ−2 ± 2 µmol/L, p < 0.01) and FMD (Δ1.4 ± 2.0% vs. Δ−0.5 ± 1.7%, p = 0.03) compared to PL. Resting aortic diastolic BP (Δ−2 ± 4 vs. Δ2 ± 5 mmHg, p = 0.01) and mean arterial pressure (Δ−2 ± 4 vs. Δ2 ± 6 mmHg, p = 0.04) were significantly decreased after 4 weeks of L-CIT compared to PL. Although not statistically significant (p = 0.07), cfPWV decreased after L-CIT supplementation by ~0.66 m/s. These findings suggest that L-CIT supplementation improves endothelial function and aortic BP via increased L-ARG availability.     

Branched-Chain Amino Acids Supplementation Does Not Accelerate Recovery after a Change of Direction Sprinting Exercise Protocol

BCAAs supplementation has been widely used for post-exercise recovery. However, no evidence is currently available to answer the question of whether BCAAs supplementation can attenuate muscle damage and ameliorate recovery after a bout of change of direction (COD) sprinting, which is an exercise motion frequently used during team sport actions. This study aimed to assess the effect of BCAAs supplementation on muscle damage markers, subjective muscle soreness, neuromuscular performance, and the vascular health of collegiate basketball players during a 72 h recovery period after a standardized COD protocol. Participants orally received either BCAAs (0.17 g/kg BCAAs + 0.17 g/kg glucose) or placebo (0.34 g/kg glucose) supplementation before and immediately after a COD exercise protocol in a randomized, crossover, double-blind, and placebo-controlled manner. Creatine kinase increased immediately after exercise and peaked at 24 h, muscle soreness remained elevated until 72 h, whilst arterial stiffness decreased after exercise for both supplemented conditions. A negligibly lower level of interleukin-6 was found in the BCAAs supplemented condition. In conclusion, the results of this study do not support the benefits of BCAAs supplementation on mitigating muscle damage and soreness, neuromuscular performance, and arterial stiffness after COD for basketball players.     

Encapsulated bacteria deform lipid vesicles into flagellated swimmers

We study a synthetic system of motile Escherichia coli bacteria encapsulated inside giant lipid vesicles. Forces exerted by the bacteria on the inner side of the membrane are sufficient to extrude membrane tubes filled with one or several bacteria. We show that a physical coupling between the membrane tube and the flagella of the enclosed cells transforms the tube into an effective helical flagellum propelling the vesicle. We develop a simple theoretical model to estimate the propulsive force from the speed of the vesicles and demonstrate the good efficiency of this coupling mechanism. Together, these results point to design principles for conferring motility to synthetic cells.

The interaction of active and passive matter lies at the heart of biology. Active matter (1) consists of collections of entities that consume energy from their environment to generate mechanical forces, which often result in motion. Thus, the cell membrane, whose essential component is a passive lipid bilayer, can actively remodel during cell growth; motility; and, ultimately, cell evolution, under the forces exerted by a host of active agents. For example, continuous polymerization–depolymerization of actin in the cytoskeleton deforms the eukaryotic cell membrane into two- and one-dimensional protrusions (lamellipodia and filopodia) that can move the whole cell (2, 3). Similar actin-supported membrane protrusions are thought to have facilitated the accidental engulfment of bacteria that led to the emergence of eukaryotic cells (4). The biophysics of active membranes has therefore been subjected to interdisciplinary scrutiny (5). More recently, learning how to create active membranes systems that deform, divide, and propel has become a priority area in the drive to synthesize life ab initio (6).Lipid vesicles enclosing natural or artificial microswimmers are becoming a model system for studying active membranes in vitro (7–15). Such composites have also direct biological relevance. For instance, from inside their eukaryotic hosts, bacterial pathogens such as Rickettsia rickettsii or Listeria monocytogenes (16, 17) continue their life cycles by hijacking the actin polymerization–depolymerization apparatus of their hosts and pushing out a tube-like protuberance from the plasma membrane. The pathogens then contact other host cells or escape into the surrounding medium by means of these membrane tubes (18).To date, research in coupling swimmers with membranes has mostly been theoretical and numerical. Such models have predicted a range of interfacial morphological changes and, in some cases, net motion of the interface (7–13). The experimental realization of these systems was only recently achieved by encapsulating swimming Bacillus subtilis bacteria (14) and synthetic Janus particles (15) in giant lipid vesicles. Both experiments reported nonequilibrium membrane fluctuations and vesicle deformations, ranging from tubular protrusions to dendritic shapes. However, net motion of the vesicles was not observed in either case.Here we present a similar experimental design but with markedly different outcome. Escherichia coli, another common motile bacterium, also extrudes membrane tubes but in addition sets the whole vesicle into motion. We demonstrate that such motion is due to a physical coupling between the flagella bundle of the enclosed cells and the tubes. The tube–flagella composite functions as a helical propeller for the entire vesicle.In biology, the specificity of interactions between bacteria and the membranes of eukaryotic hosts underlies the plethora of parasitic and symbiotic relations that have emerged between cells (18–20). Likewise, our observations illustrate the importance of small details in the design of active matter systems (21). Encapsulated bacteria propelled by a single bundle of helical flagella can generate net motion of the vesicles, whereas encapsulated swimmers propelled at similar speeds by phoresis fail to do so (15). These observations illustrate the fact that it is dangerous to proceed from coarse-grained simulations or theory that neglect such details to predict the behavior of particular systems. At the same time, our results point to a design principle for conferring motility to artificial cell models.     

MicroRNAs in laser-induced choroidal neovascularization in mice and rats: their expression and potential therapeutic targets

Choroidal neovascularization characterizes wet age-related macular degeneration. Choroidal neovascularization formation involves a primarily angiogenic process that is combined with both inflammation and proteolysis. A primary cause of choroidal neovascularization pathogenesis is alterations in pro-and anti-angiogenic factors derived from the retinal pigment epithelium, with vascular endothelium growth factor being mainly responsible for both clinical and experimental choroidal neovascularization. MicroRNAs(miRNAs) which are short, non-coding, endogenous RNA molecules have a major role in regulating various pathological processes, including inflammation and angiogenesis. A review of recent studies with the mouse laser-induced choroidal neovascularization model has shown alterations in miRNA expression in choroidal neovascularization tissues and could be potential therapeutic targets for wet age-related macular degeneration. Upregulation of miR-505(days 1 and 3 post-laser), miR-155(day 14) occurred in retina; miR-342-5 p(days 3 and 7), miR-126-3 p(day 14) in choroid; miR-23 a, miR-24, miR-27 a(day 7) in retina/choroid; miR-505(days 1 and 3) in retinal pigment epithelium/choroid; downregulation of miR-155(days 1 and 3), miR-29 a, miR-29 b, miR-29 c(day 5), miR-93(day 14), miR-126(day 14) occurred in retinal pigment epithelium/choroid. Therapies using miRNA mimics or inhibitors were found to decrease choroidal neovascularization lesions. Choroidal neovascularization development was reduced by overexpression of miR-155, miR-188-5 p, miR-(5,B,7), miR-126-3 p, miR-342-5 p, miR-93, miR-126, miR-195 a-3 p, miR-24, miR-21, miR-31, miR-150, and miR-184, or suppression of miR-505, miR-126-3 p, miR-155, and miR-23/27. Further studies are warranted to determine miRNA expression in mouse laser-induced choroidal neovascularization models in order to validate and extend the reported findings. Important experimental variables need to be standardized; these include the strain and age of animals, gender, number and position of laser burns to the eye, laser parameters to induce choroidal neovascularization lesions including wavelength, power, spot size, and duration.     

WATER METABOLISM IN HYPERTENSIVE RATS

The water intake in hypertensive rats was investigated. Rats made hypertensive by renal ischemia increased their water consumption by 75 per cent over the preoperative level. Polyuria was associated with this polydipsia and the independence of these occurrences from a number of other factors was demonstrated. It was found that the presence of a normal kidney exerted a compensatory influence which may mask either hypertension or polyuria or both. The appearance or exacerbation of the changes upon removal of the normal kidney, on the one hand, and the elimination or mitigation of the symptoms upon removal of the ischemic kidney on the other support the view that the changes observed cannot have been due to passive elimination of the kidney tissue by ischemia, but to active malfunction of the renal, and especially the tubular, mechanism upon withdrawal of oxygen. The view is put forward that polyuria is a primary sequel of ischemia rather than secondary to the intra- and extrarenal effects of hypertension. A number of concomitant observations are in harmony with this hypothesis.     

Potential Benefits of the Mediterranean Diet and Physical Activity in Patients with Hidradenitis Suppurativa: A Cross-Sectional Study in a Spanish Population

There is scarce scientific information regarding the potential benefits of healthy lifestyles in patients with hidradenitis suppurativa (HS). The objective of this study is to explore the potential association between the adherence to a Mediterranean diet (MD), physical activity and HS severity. A cross-sectional study that included patients with HS was conducted. Disease severity was evaluated by the International Hidradenitis Suppurativa Severity Score System (IHS4) and self-reported disease activity using a Numeric Rating Scale (NRS, 0–10). The adherence to a MD was assessed by the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire and the level of physical activity by the International Physical Activity questionnaire. A total of 221 patients with HS were included in our study. The adherence to a MD was average for a Spanish population. A higher adherence to a MD was associated with lower disease activity, lower self-reported Hurley and lower IHS4. The use of extra virgin olive oil as the main culinary lipid was the dietary habit that implied a lower degree of disease activity (p < 0.05). Regarding physical activity, both the self-reported severity and IHS4 presented an inverse association with the intensity of physical activity. The adherence to a MD and the intensity of physical activity were positively associated. The Mediterranean dietary pattern may have an impact on HS. Greater adherence to a MD is related to lower HS severity and more physical activity also correlates to lower disease severity. The MD could be an appropriate dietary pattern for patients with HS due to its anti-inflammatory properties, and combining this with increased levels of physical activity could have additional benefits.