A systematic review of irreversible electroporation in localised prostate cancer treatment

Irreversible electroporation is a treatment option used for focal therapy. In this systematic review, we summarise data on irreversible electroporation outcomes in patients with localised prostate cancer. We performed a literature search in 3 databases and included articles with own data on irreversible electroporation results in patients with localised prostate cancer. Primary outcome was procedure efficacy measured as the absence of cancer in the treatment area on the follow-up biopsy. Secondary outcomes were the absence of prostate cancer recurrence in the treatment area on MRI, out-of-field recurrence, complications and functional outcomes (erectile function and micturition). In-field recurrence rate was 0%–39% and out-field 6.4%–24%. In all studies, PSA level decreased: twice lower than baseline after 4 weeks and by 76% after 2 years. Most of the authors noted sexual and urinary toxicity during the first half year after surgery. However, functional outcomes recovered to baseline after 6 months with mild decrease in sexual function. Complication rates after irreversible electroporation were 0%–1% of Clavien–Dindo III and 5%–20% of Clavien–Dindo I–II. Irreversible electroporation has promise oncological outcomes, rate of post-operative complications and minimal-to-no effects on erectile and urinary function. However, medium and long-term data on cancer-specific and recurrence-free survival are still lacking.     

Predicting Psychosocial Outcomes Using a Brief Measure of Quality of Life in a Sample of People with Spinal Cord Injury

Background:

Spinal cord injury (SCI) significantly impacts an individual’s quality of life (QOL). A brief and subjective measure of QOL is necessary to monitor the progress and outcomes of SCI rehabilitation.

Objective:

To determine whether this measure of QOL was associated with clinically important physical and psychosocial outcomes in a sample of people with SCI, to determine how people with SCI scored on this measure of QOL, and to determine whether people with SCI scored differently than nondisabled individuals on the QOL scale.

Methods:

Participants were 134 people with SCI (65% male; 35% female) and 227 nondisabled people (35% male; 65% female). Participants were assessed on a number of psychosocial and physiological variables at a large urban university and rehabilitation center. Variables examined were QOL, life satisfaction, depression, social interaction, pain, fatigue, and level of functioning.

Results:

Participants with SCI reported more low QOL scores and fewer high QOL scores than the nondisabled group. For participants with SCI, QOL was positively related to life satisfaction and social interaction and negatively related to pain, fatigue, and depression.

Conclusions:

Participants with SCI scored lower on the QOL measure than those without a disability, although the difference was not clinically significant. QOL was unrelated to level of functioning; people may still experience a high QOL despite their physical limitations. Depression and social interaction were significantly related to QOL and should be secondary targets for intervention following SCI rehabilitation.Key words: depression, disability, life satisfaction, pain, quality of life, social interaction, spinal cord injuriesQuality of life (QOL) can be defined as the quality of a person’s overall experiences of living. Individuals differ on what values they place on work, leisure activities, relationships with other people, intimacy with a spouse or partner, or participation in sports. Perhaps no other impairment impacts a person’s QOL as much as a spinal cord injury (SCI).¹ After the medical and functional problems are addressed in rehabilitation, individuals begin to think about how they can regain much of their previous lifestyle and QOL. There are substantial barriers in the physical and social environments that stand in the way of higher QOL, including medical issues; difficulties in constructing a suitable home environment; and challenges in keeping the family together, supporting oneself, and dealing with the subtle and not-so-subtle attitudes of others.² These problems and barriers can result in psychological issues, the most common of which is depression.³ It is not surprising that individuals find it difficult to regain a positive level of QOL after SCI.Considering that there are approximately 270,000 people currently living with SCI in the United States, with 12,000 new cases of SCI each year,⁴ the topic of QOL is important to the persons with SCI, their families, and to the clinicians who treat them. However, there is little agreement on the definition of QOL and therefore on its measurement. Most measures of QOL are either too long for clinicians to use in practice or are not measures of QOL itself, but rather are measures of life satisfaction, health status, or well-being. For example, The World Health Organization’s⁵ QOL measure, WHOQOL-BREF, is primarily a life satisfaction measure, and it takes more than 1 hour to administer. Even the SF-36,⁶ which many people inaccurately accept and use as a measure of QOL, is actually a measure of health status, according to the author.Experts in both QOL and SCI, including Dijkers⁷ and Tate,⁸ have argued that there is a need for a subjective measure of QOL that can be used to monitor a person’s progress of rehabilitation and as a measurable outcome of rehabilitation programs. Clinical practice requires brief measures that are reliable and valid and that can be incorporated into progress notes about the patient. This clinically oriented article addresses the issue of whether a brief measure of QOL can stand up to the rigors of scientific standards while still predicting clinically important outcomes of SCI and whether it is suitable for the practitioner as well as for persons with SCI.This article addresses 3 objectives. The first objective was to determine whether this measure of QOL was associated with clinically important physical and psychosocial outcomes in a sample of people with SCI. The second objective was to determine how people with SCI scored on this measure of QOL. The third objective was to determine whether people with SCI scored differently than nondisabled individuals on a subjective, single-item QOL scale.     

Critical Dynamics of Defects and Mechanisms of Damage-Failure Transitions in Fatigue

An experimental methodology was developed for estimating a very high cycle fatigue (VHCF) life of the aluminum alloy AMG-6 subjected to preliminary deformation. The analysis of fatigue damage staging is based on the measurement of elastic modulus decrement according to “in situ” data of nonlinear dynamics of free-end specimen vibrations at the VHCF test. The correlation of fatigue damage staging and fracture surface morphology was studied to establish the scaling properties and kinetic equations for damage localization, “fish-eye” nucleation, and transition to the Paris crack kinetics. These equations, based on empirical parameters related to the structure of the material, allows us to estimate the number of cycles for the nucleation and advance of fatigue crack.     

Anodic Electrodeposition of Chitosan–AgNP Composites Using In Situ Coordination with Copper Ions

Chitosan is an attractive material for biomedical applications. A novel approach for the anodic electrodeposition of chitosan–AgNP composites using in situ coordination with copper ions is proposed in this work. The surface and cross-section morphology of the obtained coating with varying concentrations of AgNPs were evaluated by SEM, and surface functional groups were analyzed with FT-IR spectroscopy. The mechanism of the formation of the coating based on the chelation of Cu(II) ions with chitosan was discussed. The antibacterial activity of the coatings towards Staphylococcus epidermidis ATCC 35984/RP62A bacteria was analyzed using the live–dead approach. The presented results indicate that the obtained chitosan–AgNP-based films possess some limited anti-biofilm-forming properties and exhibit moderate antibacterial efficiency at high AgNP loads.     

Noninvasive Assessment of the Fractional Flow Reserve with the CT FFRc 1D Method: Final Results of a Pilot Study

Background:Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling.Objective:The research aims to evaluate the diagnostic accuracy of this algorithm.Methods:The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography – included retrospectively, 64 – prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland–Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman’s rank correlation coefficient.Results:During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71–82.03); the specificity was 78.95% (95% CI: 56.67–91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13–84.40); the specificity was 87.50% (95% CI: 52.91–99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97–88.08), p < 0.0001.Conclusion:The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97–88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power.     

1,2-Benzoxathiin-4(3H)-one 2,2-dioxide – new enol nucleophile in three-component interaction with benzaldehydes and active methylene nitriles

The reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was studied in multicomponent type reactions for the first time, namely, in a three-component interaction with active methylene nitriles and aromatic aldehydes in order to construct condensed 2-amino-4H-pyran derivatives. The reaction outcome strongly depended on the nature of an active methylene nitrile and an arenecarbaldehyde. Application of malononitrile resulted in novel 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides in most cases, whereas the utilization of ethyl cyanoacetate resulted in a complex mixture of products. In the last case, three different products were isolated depending on the arenecarbaldehyde used, namely ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides, ethyl 2-cyano-3-arylacrylates, and salts of 3,3′-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides). Attempts to obtain separately ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides enabled us to propose reaction pathways leading to these products. The salts were obtained for the first time. The preparative method for the synthesis of triethylammonium salts of 3,3′-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides) was proposed by the direct interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with arenecarbaldehydes. The application of ammonium acetate as a catalyst allowed us to synthesize 7-aryl-7,14-dihydrobenzo[5,6][1,2]oxathiino[4,3-b]benzo[5,6][1,2]oxathiino[3,4-e]pyridine 6,6,8,8-tetraoxides containing a novel heterocyclic system. These facts, combined with our past investigations, allowed us to assert that the reactivity of enol nucleophiles that include the COCH₂SO₂X fragment has not been reported previously.

Reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was for the first time studied in multicomponent type reactions involving active methylene nitriles and aromatic aldehydes.     

Towards sustainable diagnostics: replacing unstable H2O2 by photoactive TiO2 in testing systems for visible and tangible diagnostics for use by blind people

Blind and color blind people cannot use colorimetric diagnostics; the problem is especially severe in rural areas where high temperatures and the absence of electricity challenge modern diagnostics. Here we propose to replace the unstable component of a diagnostic test, H₂O₂, with stable TiO₂. Under UV irradiation, TiO₂ forms reactive oxygen species that initiate polymerization of acrylamide causing liquid-to-gel transition in an analyte-dependent manner. We demonstrate that specific DNA sequences can be detected using this approach. This development may enable the detection of biological molecules by users with limited resources, for example in developing countries or for travelers in remote areas.

Blind and color blind people cannot afford colorimetric diagnostics; the problem is especially severe in rural areas where high temperatures and the absence of electricity challenge modern diagnostics.

An ideal diagnosis, including diagnosis for infectious diseases, should meet the ASSURED criteria: (i) affordable by those at risk of infection; (ii) sensitive; (iii) specific; (iv) user-friendly; (v) rapid, and robust, for example not requiring refrigerated storage; (vi) equipment-free; (vii) delivered to those who need it.¹Analytic methods with visually detectable outputs (e.g. color change) satisfy criteria (iv) and (vi), and are therefore among the most common. Indeed, pregnancy tests, test strips for measuring acetone and glucose in urine for diabetic people, and pH strips are known to be the best to make the analysis easiest in data output. However, such methods cannot be used by the visually impaired.Recently, we described an alternative output signal that cannot only be detected by sight, but also by touch and applied it in the detection of adenosine triphosphate (ATP) and deoxyribonucleic acid (DNA).² The method is based on the analyte-dependent radical polymerization of acrylamide into polyacrylamide in the presence of hydrogen peroxide (H₂O₂). H₂O₂ serves as a source of radicals. The test uses affordable reagents and does not require any instrumentation for signal readout. Such test systems can be adopted for detection of a wide variety of biological analytes. Unfortunately, H₂O₂ is subject to light decomposition and should be refrigerated for long term storage; it is also prone to exploding at high concentrations. Therefore, substituting H₂O₂ with a more stable ingredient would increase the shelf life of the test system and make it usable in those environments with limited access to refrigeration. This work is devoted to addressing the ASSURED criterion (v): we substituted perishable H₂O₂ with stable titania (TiO₂) as an alternative source of initiators of radical polymerization.Recently we demonstrated the possibility of converting electromagnetic energy into pH gradients³ or generating reactive oxygen species (ROS) using TiO₂,^3,4 which makes this approach attractive for controlling interactions between chemical networks. Moreover, combining several functional chemical networks can result in a network with new functions. We have also shown that the pH gradient on titania can be used for regulating enzymatic reaction networks.⁵ In this work, we were interested in using photogenerated ROS (such as superoxide anion O₂˙⁻, hydroxyl radical ˙OH, and hydrogen peroxide H₂O₂) (Fig. 1) to initiate radical polymerization with the aim of making a visual and tactile portable sensor for the detection of biologically important molecules (DNA, RNA, ATP). Under ultraviolet (UV) irradiation, TiO₂ splits water, which results in the generation of a high concentration of ROS and free radicals.⁶Open in a separate windowFig. 1(i) A portable sensor based on a light-induced liquid-to-gel transition for polymer by radical polymerization on TiO₂ particles. The details of the sensor design are shown in Fig. 5; (ii) ROS formation on titania via reactions with photogenerated photohole (h⁺) and photoelectron (e⁻).The sensing system is based on deoxyribozyme sensor that produces ROS in the presence of a specific analyte, thereby triggering the radical polymerization of acrylamide into polyacrylamide. The buffer contained acetylacetone, H₂O₂, 40% acrylamide/bisacrylamide, hemin and a split deoxyribozyme sensor with peroxidase-like activity (PxR).² In the presence of the specific analyte sequence (A1 in this study), the sensor hybridized with the analyte and formed PxR, which bound hemin and decomposed H₂O₂ to ROS. The latter oxidized acetylacetone to the acetylacetone radical, which initiated the polymerization of acrylamide, resulting in liquid-to-gel conversion. Here, the aim of the research is to increase the system sustainability by changing H₂O₂ to TiO₂ particles. Noteworthy is that the system is externally controlled by UV light, since TiO₂ produces ROS only upon irradiation.Firstly, we quantified the TiO₂-derived ROS with the aim of finding the optimal conditions for the generation of the minimum amount of ROS needed for the polymerization. We used luminol chemiluminescence (CL) calibrated with hydrogen peroxide. Luminol (5-amino-2,3-dihydro-1,4-phthalazinedione) is a widely used CL reagent and has CL emission at different wavelengths depending on the conditions.⁶ Traditionally, luminol CL is observed in the presence of H₂O₂ in alkaline solutions (Fig. 2), which is catalyzed by metal ions, metal complexes or vitamins.^7–10Open in a separate windowFig. 2Mechanism of chemiluminescence of luminol and O₂⁻˙.The luminol CL signaling is conveniently used for the detection of ROS (particularly superoxide anion, hydrogen peroxide, hydroxyl radical) in biological systems.^11–16Irradiation of TiO₂ suspensions of different concentrations (0.03 M and 0.06 M) at two wavelengths (365 nm and 254 nm) revealed more ROS being formed upon irradiation at 254 nm – as was expected (Fig. 3).Open in a separate windowFig. 3Log concentration of ROS generated in TiO₂ suspensions of different concentration (0.03 M and 0.06 M) under irradiation by UV light with different wavelengths vs. irradiation time.According to the data obtained, the minimum concentration of TiO₂ needed to trigger polymerization after 5 min of irradiation at 365 nm was 1.25 mM (Fig. 4). We therefore used these conditions in the following experiments, since short irradiation time and longer wavelength of UV-A irradiation are less damaging to the DNA-based biosensor component than UV-C light with wavelength of 254 nm. It should be noted that control experiments were made without TiO₂ particles and polymerization did not occur. Next, we optimized the conditions for the analyte-dependent activation of PxR resulting in acrylamide polymerization. If polymerization occurs, the gel will stick to the bottom of the inverted tubes (Fig. 5).² To demonstrate the general applicability of the approach, we designed a sensor for an analyte of biomedical significance, nucleic acids, as an example. A sequence of 16S rRNA, which was represented in this study by synthetic A1 sequence (5′-CAT TAC TCA CCC GTC CGC CAC TCG TCA GCG AAG CAG CAA GCT GCT TCC TGT TAC CGT TCG), of pathogenic E. coli O157:H7 was chosen as the target analyte,. The binding of A1 to PxR1 and PxR2 stabilized the G-quadruplex structure, which then binds to hemin and catalyzes the polymerization (Fig. 5A).Open in a separate windowFig. 4The dependence of the log concentration of ROS generated on TiO₂ particles on TiO₂ suspension concentration. Inserts show the minimum concentration of TiO₂ particles in a suspension (therefore minimum concentration of ROS generated on TiO₂ particles), needed for the gel formation.Open in a separate windowFig. 5Polymerization-based visual and tactile detection of A1 analyte. (A) Sensor design: RNA strands PxR1 and PxR2 bind A1 sequence and form a G-quadruplex structure, which then binds to hemin (green oval) and catalyzes the radical polymerization of the acrylamide solution. The dotted lines represent triethylene glycol linkers. (B and C) Inverted test-tubes with radical polymerization of acrylamide initiated by reactive oxygen species generated on TiO₂ particles under UV light 365 nm. (B) Systems with different concentrations of hemin (

Molecular pathways of liver regeneration: A comprehensive review

The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70% of its volume. Although knowledge of this phenomenon dates back to Greek mythology(the story of Prometheus), many aspects of liver regeneration are still not understood. A variety of different factors, including inflammatory cytokines, growth factors, and bile acids, promote liver regeneration and control the final size of the organ during typical regeneration, which is performed by mature hepatocytes, and during alternative regeneration, which is performed by recently identified resident stem cells called "hepatic progenitor cells". Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass, such as in cases of chronic injury or excessive acute injury. In liver maintenance, the body mass ratio is essential for homeostasis because the liver has numerous functions; therefore, a greater understanding of this process will lead to better control of liver injuries, improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases. The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries. Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.     

Integrase Strand Transfer Inhibitors Are Effective Anti-HIV Drugs

Integrase strand transfer inhibitors (INSTIs) are currently recommended for the first line treatment of human immunodeficiency virus type one (HIV-1) infection. The first-generation INSTIs are effective but can select for resistant viruses. Recent advances have led to several potent second-generation INSTIs that are effective against both wild-type (WT) HIV-1 integrase and many of the first-generation INSTI-resistant mutants. The emergence of resistance to these new second-generation INSTIs has been minimal, which has resulted in alternative treatment strategies for HIV-1 patients. Moreover, because of their high antiviral potencies and, in some cases, their bioavailability profiles, INSTIs will probably have prominent roles in pre-exposure prophylaxis (PrEP). Herein, we review the current state of the clinically relevant INSTIs and discuss the future outlook for this class of antiretrovirals.