'Essential' arterial hypertension: time for a paradigm change.

The exclusion of causes of hypertension is not systematically exploited in clinical practice. Therefore, essential hypertension is consistently presented as the most prevalent 'cause'. The paradox of a condition with unknown causes being described as a common cause of hypertension translates into a diagnosis of essential hypertension in most patients, which precludes the detection of a curable cause of hypertension. The aim of this review is to investigate how the notion of essential hypertension has developed and whether scientific evidence still support the notion of its high prevalence by examining the most recent studies. These studies provided solid scientific evidence that, when systematically sought for, secondary hypertension is quite common and that secondary hypertension is highly prevalent. The increased awareness should lead to a systematic search for, with the goal of curing or achieving a better control of high blood pressure, and ultimately improving patients' quality of life.

Bioprospecting for plant resilience to climate change: mycorrhizal symbionts of European and American beachgrass (Ammophila arenaria and Ammophila breviligulata) from maritime sand dunes.

Climate change and global warming have contributed to increase terrestrial drought, causing negative impacts on agricultural production. Drought stress may be addressed using novel agronomic practices and beneficial soil microorganisms, such as arbuscular mycorrhizal fungi (AMF), able to enhance plant use efficiency of soil resources and water and increase plant antioxidant defence systems. Specific traits functional to plant resilience improvement in dry conditions could have developed in AMF growing in association with xerophytic plants in maritime sand dunes, a drought-stressed and low-fertility environment. The most studied of such plants are European beachgrass (Ammophila arenaria Link), native to Europe and the Mediterranean basin, and American beachgrass (Ammophila breviligulata Fern.), found in North America. Given the critical role of AMF for the survival of these beachgrasses, knowledge of the composition of AMF communities colonizing their roots and rhizospheres and their distribution worldwide is fundamental for the location and isolation of native AMF as potential candidates to be tested for promoting crop growth and resilience under climate change. This review provides quantitative and qualitative data on the occurrence of AMF communities of A. arenaria and A. breviligulata growing in European, Mediterranean basin and North American maritime sand dunes, as detected by morphological studies, trap culture isolation and molecular methods, and reports on their symbiotic performance. Moreover, the review indicates the dominant AMF species associated with the two Ammophila species and the common species to be further studied to assess possible specific traits increasing their host plants resilience toward drought stress under climate change.

Neuroimmunomodulatory effect of Nitric Oxide on chronic wound healing after photodynamic therapy.

Neuroimmunomodulation is the capacity of the nervous system to regulate immune processes. The existence of neurotransmitter receptors in immune cells enables this phenomenon to take place. Neuronal mediators possess the capacity to direct and control several occurrences during the wound healing process. Nitric oxide (NO) functions as a neuromodulator, playing a crucial role in the regulation of vascular tone and blood pressure with antimicrobial properties. Photodynamic therapy has been shown to augment the function of immune cells involved in the healing process of venous leg ulcers. Nitric oxide can be secreted into the extracellular environment by these cells. In lesions treated with PDT, the synthesis of iNOs (the enzyme that releases NO) increased, as demonstrated by the experimental results. Therefore the significance of PDT in enhancing the clinical condition of the lesion is thus highlighted.

Mild hydrolysis of chemically stable valerolactams by a biocatalytic ATP-dependent system fueled by metaphosphate.

Medium-sized 5- and 6-membered ring lactams are molecules with remarkable stability, in contrast to smaller ß-lactams. As monomers, they grant access to nylon-4 and nylon-5, which are alternative polyamides to widespread caprolactam-based nylon-6. Chemical hydrolysis of monocyclic γ- and δ-lactams to the corresponding amino acids requires harsh reaction conditions and up to now, no mild (enzymatic) protocol has been reported. Herein, the biocatalytic potential of a pair of heterologously expressed bacterial ATP-dependent oxoprolinases - OplA and OplB - was exploited. Strong activity in the presence of excess of ATP was monitored on δ-valerolactam and derivatives thereof, while trace activity was detected on γ-butyrolactam. An ATP recycling system based on cheap Graham's salt (sodium metaphosphate) and a polyphosphate kinase allowed the use of catalytic amounts of ATP, leading to up to full conversion of 10 mM δ-valerolactam at 30 °C in aqueous medium. Further improvements were obtained by co-expressing OplA and OplB using the pETDuet1 vector, a strategy which enhanced the soluble expression yield and the protein stability. Finally, a range of phosphodonors was investigated in place of ATP. With acetyl phosphate and carbamoyl phosphate, turnover numbers up to 176 were reached, providing hints on a possible mechanism, which was studied by 31P-NMR.

Increased genomic instability and reshaping of tissue microenvironment underlie oncogenic properties of Arid1a mutations.

Oncogenic mutations accumulating in many chromatin-associated proteins have been identified in different tumor types. With a mutation rate from 10 to 57%, ARID1A has been widely considered a tumor suppressor gene. However, whether this role is mainly due to its transcriptional-related activities or its ability to preserve genome integrity is still a matter of intense debate. Here, we show that ARID1A is largely dispensable for preserving enhancer-dependent transcriptional regulation, being ARID1B sufficient and required to compensate for ARID1A loss. We provide in vivo evidence that ARID1A is mainly required to preserve genomic integrity in adult tissues. ARID1A loss primarily results in DNA damage accumulation, interferon type I response activation, and chronic inflammation leading to tumor formation. Our data suggest that in healthy tissues, the increased genomic instability that follows ARID1A mutations and the selective pressure imposed by the microenvironment might result in the emergence of aggressive, possibly immune-resistant, tumors.

Radiographic evaluation of marginal bone levels around implants supporting splinted fixed bridges: A retrospective study on 412 implants.

OBJECTIVES: The effect of the implant position within the prosthesis on bone remodeling is scarcely documented so far. Thus, the aim of the present study was to investigate whether central implants may suffer higher peri-implant marginal bone levels (MBL) compared to laterals in case of fixed splinted bridges supported by ≥ three implants. MATERIALS AND METHODS: Partially edentulous subjects rehabilitated with at least one fixed bridge supported by ≥ three dental implants were enrolled. MBL was assessed radiographically by means of intraoral radiographs acquired with phosphor plates and imported in a dedicated software. MBL was calculated as the distance between the implant platform level and the most coronal visible bone-to-implant contact. A three-level linear mixed effects model was used for investigating the fixed effect of patient-, prosthesis-, and implant-level variables on the MBL. RESULTS: Overall, 90 patients rehabilitated with 130 splinted fixed bridges supported by 412 implants were included. The median follow-up was 136 months. The mean peri-implant MBL resulted statistically significantly higher at central implants if compared to lateral implants (p < .01). The estimated MBL averages for central and external implants were 1.68 and 1.18 mm, respectively. The prosthesis-level variables suggested that a cement-retained bridge was prone to a significant 0.82 mm higher MBL than a screw-retained one. Implant surface showed an association with MBL changes, although less pronounced than implant retention. CONCLUSIONS: In case of ≥3 adjacent implants supporting splinted bridges, central implants were more predisposed to MBL compared to laterals. At the prosthesis level, implants supporting cement-retained bridges were statistically more susceptible to MBL compared to screw-retained ones. Surface characteristics can also influence MBL stability at the implant level.

Specific anion effects on urease activity: A Hofmeister study.

The effects of a range of electrolytes on the hydrolysis of urea by the enzyme urease is explored. The autocatalytic behavior of urease in unbuffered solutions and its pH clock reactions are studied. The concentration dependence of the experimental variables is analyzed in terms of specific ion-enzyme interactions and hydration. The results offer insights into the molecular mechanisms of the enzyme, and on the nature of its interactions with the electrolytes. We found that urease can tolerate mild electrolytes in its environment, while it is strongly inhibited by both strong kosmotropic and strong chaotropic anions. This study may cast light on an alternative therapy for Helicobacter pylori infections and contribute to the design of innovative materials and provide new approaches for the modulation of the enzymatic activity.

The effect of a protective layer on the optical behavior of retro-reflective paintings for building envelopes.

Retro-reflective (RR) materials, applied to building envelopes, constitute an option to tackle Urban Heat Island phenomenon, thanks to their capability to reflect the sunlight predominantly towards the solar incidence direction. RR coatings are obtained with the deposition of glass beads on traditional diffusive materials. During their lifetime, outdoor aging and soiling affect their optical behavior. In addition, without a proper protection, some glass beads could detach from the paint and disperse in the environment. Hence, a necessity arises for the application of a safeguarding stratum on RR materials to avert the separation of glass beads in RR coatings following the aging process. In this paper, five RR samples were produced, employing a highly reflective paint as foundation, RR glass beads and a protective layer. A diffusive sample, without glass beads, was made for comparison. Samples underwent spectrophotometric and angular distribution analyses. The effect of the protective layer on the optical behavior was assessed comparing the results with those obtained for the same RR materials without the protective layer. RR samples with a protective layer exhibit a higher reflectance with respect to the same RR sample without a protective layer. In the near-infrared (NIR) region, a lower reflectance occurs for all RR samples with a protective layer. A less concentrated angular distribution of the reflected light was observed for all RR samples with the addition of a protective layer.

Multiscale Frozen Density Embedding/Molecular Mechanics Approach for Simulating Magnetic Response Properties of Solvated Systems.

We present a three-layer hybrid quantum mechanical/quantum embedding/molecular mechanics approach for calculating nuclear magnetic resonance (NMR) shieldings and J-couplings of molecular systems in solution. The model is based on the frozen density embedding (FDE) and polarizable fluctuating charges (FQ) and fluctuating dipoles (FQFµ) force fields and permits the accurate ab initio description of short-range nonelectrostatic interactions by means of the FDE shell and cost-effective treatment of long-range electrostatic interactions through the polarizable force field FQ(Fµ). Our approach's accuracy and potential are demonstrated by studying NMR spectra of Brooker's merocyanine in aqueous and nonaqueous solutions.

Water and Electrolyte Content in Salt-Dependent HYpertension in the SKIn (WHYSKI): Effect of Surgical Cure of Primary Aldosteronism.

 INTRODUCTION: This study will test the hypothesis that primary aldosteronism (PA) involves alterations in Na+, K+, and water content in the skin that are corrected by adrenalectomy. AIM AND METHODS: In skin biopsies, we will measure the content of Na+, K+, water, by physical-chemical methods and the osmotic-stress-responsive transcription factor Tonicity-responsive Enhancer Binding Protein (TonEBP, NFAT5) mRNA copy number by droplet digital PCR, in sex-balanced cohorts of 18 -75-year-old consecutive consenting patients with unilateral and bilateral PA, primary (essential) hypertension, and normotension. Before surgery, the patients with unilateral PA will receive the mineralocorticoid receptor antagonist (MRA) canrenone at doses that correct hypokalemia and high blood pressure values. They will be reassessed in an identical way one month after surgical cure, while off MRA. PA patients not selected for adrenalectomy will similarly be assessed at diagnosis and follow-up while on stable MRA treatment. Since a pilot study showed a direct correlation of dry weight (DW) with skin electrolytes and water content and significant differences of biopsy DW between surgery and follow-up, meaningful comparison of the skin cations and water content and TonEBP mRNA copy number, between specimen obtained at different time points, will require DW- and total mRNA-adjustment, respectively. CONCLUSION: This study will provide novel information on the skin Na+, K+ and water content in PA, the paradigm of salt-dependent hypertension, and novel knowledge on the effect of surgical cure of hyperaldosteronism. The TonEBP-mediated regulation of Na+, K+ and water content in the skin will also be unveiled. TRAIL REGISTRY: Trial Registration number: NCT06090617. Date of Registration: 2023-10-19.

Synthesis of Zeolitic Imidazolate Framework-8 Using Glycerol Carbonate.

In this study, we show that glycerol carbonate (GlyC), a bio-based derivative of glycerol, can be used as a suitable green solvent for the synthesis of metal-organic frameworks (MOFs). In particular, a zinc-based zeolitic imidazolate framework-8 (ZIF-8) was synthesized by exploring several different experimental conditions (in terms of temperature, reaction time, and reactants' concentrations) to find that the yield of the reaction and the quality of the products, measured in terms of crystallinity, surface area, and porosity, were in line with those obtained in the most commonly (non-green) used solvents. GlyC was also found to be reusable for several cycles, maintaining the same original quality as a solvent for the synthesis. Finally, some indicators for the assessment of the greenness of a process (E-factor and PMI) revealed a milder environmental impact of GlyC with respect to other solvents.

Endocrine disruptors and arterial hypertension: A developing story.

Endocrine disrupting Chemicals (EDCs) are substances that interfere with hormones by several mechanisms including receptor activation or antagonism, changes in gene and protein expression, modification of signal transduction, and/or epigenetic modifications in hormone-producing cells. A survey conducted by the European Union in a Northern Italian region led to the discovery of a large environmental contamination of drinking water by perfluoroalkyl substances (PFAS). As the exposed population showed a high prevalence of arterial hypertension and cardiovascular disease, we decided to investigate if PFAS could enhance the biosynthesis of aldosterone. To this aim, we exposed human adrenocortical carcinoma HAC15 cells to PFAS and found that PFAS markedly increased aldosterone synthase (CYP11B2) gene expression and aldosterone secretion. Moreover, we found that they promoted reactive oxygen species (ROS) production in mitochondria, the organelles where aldosterone biosynthesis takes place. PFAS also enhanced the effects of the aldosterone secretagogue angiotensin II (Ang II) on CYP11B2 gene expression and aldosterone secretion. We also found that not only PFAS but also polychlorinated biphenyl 126 (PCB126), a chemical compound belonging to a different category of EDCs, can increase CYP11B2 gene expression and aldosterone secretion in adrenocortical cells. This novel information needs to be considered in the context of a widespread exposure to the most common EDC, that is excess Na+ intake, whose detrimental effects on human health occur in the setting of aldosterone production exceeding the physiological needs and lead to high blood pressure, congestion, and cardiovascular and renal damage.

Non-autonomous zinc-methylimidazole oscillator and the formation of layered precipitation structures in a hydrogel.

Oscillations are one of the intrinsic features of many animate and inanimate systems. The oscillations manifest in the temporal periodic change of one or several physical quantities describing the systems. In chemistry and biology, this physical quantity is the concentration of the chemical species. In most chemical oscillatory systems operating in batch or open reactors, the oscillations persist because of the sophisticated chemical reaction networks incorporating autocatalysis and negative feedback. However, similar oscillations can be generated by periodically changing the environment providing non-autonomous oscillatory systems. Here we present a new strategy for designing a non-autonomous chemical oscillatory system for the zinc-methylimidazole. The oscillations manifested in the periodic change of the turbidity utilizing the precipitation reaction between the zinc ions and 2-methylimidazole (2-met) followed by a partial dissolution of the formed precipitate due to a synergetic effect governed by the ratio of the 2-met in the system. Extending our idea spatiotemporally, we also show that these precipitation and dissolution phenomena can be utilized to create layered precipitation structures in a solid agarose hydrogel.

Psychiatric symptoms in Long-COVID patients: a systematic review.

Objective: People who have been infected by COVID-19 showing persistent symptoms after 4 weeks from recovery are thought to suffer from Long-COVID syndrome (LC). There is uncertainty on the clinical manifestations of LC. We undertook a systematic review to summarize the available evidence about the main psychiatric manifestations of LC. Method: PubMed (Medline), Scopus, CINHAL, PsycINFO, and EMBASE were searched until May 2022. Studies reporting estimation of emerging psychiatric symptoms and/or psychiatric diagnoses among adult people with LC were included. Pooled prevalence for each psychiatric condition was calculated in absence of control groups to compare with. Results: Thirty-three reports were included in the final selection, corresponding to 282,711 participants with LC. After 4 weeks from COVID-19 infection recovery, participants reported the following psychiatric symptoms: depression, anxiety, post-traumatic symptoms (PTS), cognitive and sleeping disturbances (i.e., insomnia or hypersomnia). The most common psychiatric manifestation resulted to be sleep disturbances, followed by depression, PTS, anxiety, and cognitive impairment (i.e., attention and memory deficits). However, some estimates were affected by important outlier effect played by one study. If study weight was not considered, the most reported condition was anxiety. Conclusions: LC may have non-specific psychiatric manifestations. More research is needed to better define LC and to differentiate it from other post-infectious or post-hospitalization syndromes. Systematic review registration: PROSPERO (CRD42022299408).

Effect of in vitro simulated digestion on the anti-Helicobacter Pylori activity of different Propolis extracts.

Helicobacter pylori (HP) is among the most common pathogens causing infection in humans worldwide. Oxidative stress and gastric inflammation are involved in the progression of HP-related gastric diseases, and they can be targeted by integrating conventional antibiotic treatment with polyphenol-enriched natural products. In this work, we characterised three different propolis extracts and evaluated their stability under in vitro simulated gastric digestion, compared to their main constituents alone. The extract with the highest stability to digestion (namely, the dark propolis extract, DPE) showed a minimum bactericidal concentration (MBC) lower than 1 mg/mL on HP strains with different virulence factors. Finally, since urease is one of the virulence factors contributing to the establishment of a microenvironment that promotes HP infection, we evaluated the possible inhibition of this enzyme by using molecular docking simulations and in vitro colorimetric assay, showing that galangin and pinocembrin may be involved in this activity.

Hydrodynamically-enhanced transfer of dense non-aqueous phase liquids into an aqueous reservoir.

The use of surfactants represents a viable strategy to boost the removal yield of Dense Non-Aqueous Phase Liquids (DNAPLs) from groundwater and to shorten the operational timing of the remediation process. Surfactants, in general, help in reducing the interfacial tension at the DNAPL/water interface and enhance the solubility of the pollutant in the water phase through the formation of dispersed systems, such as micelles and emulsions. In this paper, we show that a suitable choice of a surfactant, in this case belonging to the bio-degradable class of ethoxylated alcohols, allows for the formation of hydrodynamic interfacial instabilities that further enhances the dissolution rate of the organic pollutant into the water phase. In a stratified configuration (denser organic phase at the bottom and lighter water phase on top), the instabilities appear as upward-pointing fingers that originate from the inversion of the local density at the interface. This inversion stems from the synergetic coupling of two effects promoted by the ethoxylated surfactant: i) the enhanced co-solubility of the DNAPL into the water (and viceversa), and (ii) the differential diffusion of the DNAPL and the surfactant in the aqueous phase. By dissolving into the DNAPL, the surfactant also reduces locally the surface tension at the liquid-liquid interface, thereby inducing transversal Marangoni flows. In our work, we carefully evaluated the effects of the concentration of different surfactants (two different ethoxylated alcohols, sodium dodecylsulphate, cetyltrimethyl ammonium bromide, N-tetradecyl-N, N-dimethylamine oxide and bis(2-ethylhexyl) sulfosuccinate sodium salt) on the onset of the instabilities in 3 different DNAPLs/water stratifications, namely chloroform, trichloroethylene and tetrachloroethylene, with a special emphasis on the trichloroethylene/water system. By means of a theoretical model and nonlinear simulations, supported by surface tension, density and diffusivity measurements, we could provide a solid explanation to the observed phenomena and we found that the type of the dispersed system, the solubility of the DNAPL into the water phase, the solubility of the surfactant in the organic phase, as well as the relative diffusion and density of the surfactant and the DNAPL in the aqueous phase, are all key parameters for the onset of the instabilities. These results can be exploited in the most common remediation techniques.

Diamonds in the rough: Dryland microorganisms are ecological engineers to restore degraded land and mitigate desertification.

Our planet teeters on the brink of massive ecosystem collapses, and arid regions experience manifold environmental and climatic challenges that increase the magnitude of selective pressures on already stressed ecosystems. Ultimately, this leads to their aridification and desertification, that is, to simplified and barren ecosystems (with proportionally less microbial load and diversity) with altered functions and food webs and modification of microbial community network. Thus, preserving and restoring soil health in such a fragile biome could help buffer climate change's effects. We argue that microorganisms and the protection of their functional properties and networks are key to fight desertification. Specifically, we claim that it is rational, possible and certainly practical to rely on native dryland edaphic microorganisms and microbial communities as well as dryland plants and their associated microbiota to conserve and restore soil health and mitigate soil depletion in newly aridified lands. Furthermore, this will meet the objective of protecting/stabilizing (and even enhancing) soil biodiversity globally. Without urgent conservation and restoration actions that take into account microbial diversity, we will ultimately, and simply, not have anything to protect anymore.

The Lyotropic Nature of Halates: An Experimental Study.

Unlike halides, where the kosmotropicity decreases from fluoride to iodide, the kosmotropic nature of halates apparently increases from chlorate to iodate, in spite of the lowering in the static ionic polarizability. In this paper, we present an experimental study that confirms the results of previous simulations. The lyotropic nature of aqueous solutions of sodium halates, i.e., NaClO3, NaBrO3, and NaIO3, is investigated through density, conductivity, viscosity, and refractive index measurements as a function of temperature and salt concentration. From the experimental data, we evaluate the activity coefficients and the salt polarizability and assess the anions' nature in terms of kosmotropicity/chaotropicity. The results clearly indicate that iodate behaves as a kosmotrope, while chlorate is a chaotrope, and bromate shows an intermediate nature. This experimental study confirms that, in the case of halates XO3-, the kosmotropic-chaotropic ranking reverses with respect to halides. We also discuss and revisit the role of the anion's polarizability in the interpretation of Hofmeister phenomena.

Light-Switchable Membrane Permeability in Giant Unilamellar Vesicles.

In this work, giant unilamellar vesicles (GUVs) were synthesized by blending the natural phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) with a photoswitchable amphiphile (1) that undergoes photoisomerization upon irradiation with UV-A (E to Z) and blue (Z to E) light. The mixed vesicles showed marked changes in behavior in response to UV light, including changes in morphology and the opening of pores. The fine control of membrane permeability with consequent cargo release could be attained by modulating either the UV irradiation intensity or the membrane composition. As a proof of concept, the photocontrolled release of sucrose from mixed GUVs is demonstrated using microscopy (phase contrast) and confocal studies. The permeability of the GUVs to sucrose could be increased to ~4 × 10-2 µm/s when the system was illuminated by UV light. With respect to previously reported systems (entirely composed of synthetic amphiphiles), our findings demonstrate the potential of photosensitive GUVs that are mainly composed of natural lipids to be used in medical and biomedical applications, such as targeted drug delivery and localized topical treatments.