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Carbonating metallurgical slags plays a pivotal role in achieving efficient mineral CO2 sequestration and waste valorization. This research introduces a novel integrated approach that combines the carbonation of Ladle Furnace Slag (LFS) with the simultaneous degradation of Methyl Orange (MO) in synthetic water. The comprehensive characterization of LFS was conducted using X-ray Diffraction (XRD), X-ray Fluorescence (XRF), Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES), Brunauer-Emmett-Teller (BET) analysis, and Scanning Electron Microscopy (SEM). The adsorption experiments reveal the high LSF capacity for MO degradation (149.25 mg/g) following pseudo-second-order kinetics (R2 = 0.99) and Langmuir isotherm (R2 = 0.98). The adsorption process was primarily governed by chemical and electrostatic interactions. Analysis of LFS-loaded MO indicated a reduction in Ca(OH)2 phases, responsible for CO2 mineralization and the formation of calcite (CaCO3). Furthermore, the study explored the reusability of LFS-MO composites through chemical and thermal modifications. Pyrolysis of carbonated LFS with KOH impregnation exhibited potential for regenerating Ca(OH)2 phases, while thermal modification induced significant mineral and microstructural changes, creating new active sites at various temperatures. Additionally, the Fenton-like reaction followed by thermal modification resulted in a highly organized and microporous LFS structure with enhanced surface area and porosity. Moreover, modification with ZnSO4 followed by thermal activation promoted the formation of ZnO nanoxides on the LFS surface. This research proposes an innovative carbonating approach for metallurgical slags and wastewater treatment, extending their utility and enhancing industrial sustainability. Carbonated LFS-MO composites hold promise for applications in construction, CO2 capture, and wastewater treatment, thereby fostering sustainable industrial practices with ongoing research and development efforts.

Abstract Background About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims of the present study was to evaluate the “step up” approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. Methods In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). Results Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. Conclusions Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.

Summary: Post-coronavirus disease condition (PCC) continues to affect many people globally, yet there remains a lack of diagnostic biomarkers to distinguish PCC from those recovered from acute COVID-19. This study compared biomarkers between two age- and gender-matched groups: PCC individuals and those recovered within three months of acute COVID-19 in 2020 (n = 85 each). Biomarkers were assessed 12–24 months after initial diagnosis, examining biochemical profiles, blood cell counts, coagulation status, antibody serology, lymphocyte populations, and cytokine levels. PCC individuals exhibited significant alterations in 49 of 167 markers, including K+ levels, αGAD antibodies, antithrombin III, insulin-like growth factor-binding protein 3 (IGFBP3), and interleukin-10 (IL-10). A panel of αGAD, IL-10, potassium levels, and CD16brightCD56− cell presence distinguished PCC individuals from recovered patients with >88% accuracy and

Background Adoptive cell therapy using genetically modified T cells to express chimeric antigen receptors (CAR-T) has shown encouraging results, particularly in certain blood cancers. Nevertheless, over 40% of B cell malignancy patients experience a relapse after CAR-T therapy, likely due to inadequate persistence of the modified T cells in the body. IL15, known for its pro-survival and proliferative properties, has been suggested for incorporation into the fourth generation of CAR-T cells to enhance their persistence. However, the potential systemic toxicity associated with this cytokine warrants further evaluation.Methods We analyzed the persistence, antitumor efficacy and potential toxicity of anti-mouse CD19 CAR-T cells which express a membrane-bound IL15-IL15Rα chimeric protein (CD19/mbIL15q CAR-T), in BALB/c mice challenged with A20 tumor cells as well as in NSG mice.Results Conventional CD19 CAR-T cells showed low persistence and poor efficacy in BALB/c mice treated with mild lymphodepletion regimens (total body irradiation (TBI) of 1 Gy). CD19/mbIL15q CAR-T exhibits prolonged persistence and enhanced in vivo efficacy, effectively eliminating established A20 B cell lymphoma. However, this CD19/mbIL15q CAR-T displays important long-term toxicities, with marked splenomegaly, weight loss, transaminase elevations, and significant inflammatory findings in some tissues. Mice survival is highly compromised after CD19/mbIL15q CAR-T cell transfer, particularly if a high TBI regimen is applied before CAR-T cell transfer.Conclusion Tethered IL15-IL15Rα augments the antitumor activity of CD19 CAR-T cells but displays long-term toxicity in immunocompetent mice. Inducible systems to regulate IL15-IL15Rα expression could be considered to control this toxicity.

Abstract Background In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67). Methods ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging. Ancillary studies are planned PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers. Conclusion Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation. Trial registration ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

In this survey we collect some results on the influence on the structure of a group of some families of its subgroups satisfying conditions related to normality. In particular we focus on groups whose subgroups have two antagonistic properties.

El literato y periodista José Joaquín de Mora fue uno de los grandes divulgadores en castellano de la economía política en la primera mitad del siglo XIX. Aunque diversas facetas de su labor resultan ya conocidas, este no es el caso de su obra periodística sobre economía política publicada durante el sexenio absolutista (1814-1820) y el Trienio Liberal (1820-823). En este trabajo se realiza una reconstrucción íntegra de esa labor a lo largo de ese período, cuando Mora pasó de subsistir en los intersticios del absolutismo fernandino, sin ser parte de él, a participar en el liberalismo radical del Trienio. Su interés por la economía política, que se hizo expreso en la mayoría de las iniciativas periodísticas en las que estuvo implicado, pone de relieve que fue firme seguidor de los principios de la economía clásica —el librecambio incluido—, resaltando su deuda intelectual con dos grandes nombres: Say y Bentham.

IntroductionThe prairie vole (Microtus ochrogaster) is a socially monogamous species that, after cohabitation with mating, forms an enduring pair bond. It has been suggested that female prairie voles avoid mating with fathers and siblings to prevent inbreeding depression. However, controlled laboratory tests of preferences involving males with varying degree of relatedness have not been conducted.MethodsTo address this, we employed a multiple socio-sexual preference arena consisting of four adjacent cylinders arranged in a closed circle. In each cylinder, we placed a male of varying relatedness to the experimental female (i.e., father, sibling, first-degree cousin, and unrelated males) and registered their behavior for five hours. Male socio-sexual preference was determined by the proportion of time spent in each male's chamber, which can be driven by affiliative preferences for the father and sibling and sexual attraction for the cousin and unrelated males. Mating preference was analyzed as the frequency of mating with each male. We hypothesized that receptive females would show sexual attraction and mating preferences for the unrelated males and cousins and affiliative preferences for the fathers and siblings.ResultsOur analyses showed that females spent more time with first-degree cousins and mated more often with them compared to unrelated males, siblings, or fathers. However, complete inbreeding avoidance was not observed, and some females mated with siblings, fathers, or both.DiscussionAlthough our results did not support the hypothesis, they are consistent with other studies that have argued that mating with first-degree cousins optimizes the costs and benefits associated with inbreeding and outbreeding.

ABSTRACTBackground Many antimicrobial compounds in mouthwashes can have a negative impact on the oral microbiome. O-cymen-5-ol, a compound derived from a phytochemical, has a targeted mode of action and is being used as an alternative. However, its effect on the native oral microbiome is unknown.Aim To assess the effect of a mouthwash formulated with o-cymen-5-ol and zinc chloride on the oral microbiome of healthy individuals.Methods A mouthwash formulated with o-cymen-5-ol and zinc chloride was administered to a cohort of 51 volunteers for 14 days, while another cohort of 49 volunteers received a placebo. The evolution of the oral microbiome in both groups was analysed using a metataxonomic approach.Results Analysis of the oral microbiome showed that the mouthwash selectively targeted potential oral pathogens while maintaining the integrity of the rest of the microbiome. Specifically, the relative abundance of several potentially pathogenic bacterial taxa, namely Fusobacteriota, Prevotella, Actinomyces, Granulicatella, Abiotrophia, Lautropia, Lachnoanaerobaculum, Eubacterium (nodatum group) and Absconditabacteriales (SR1) decreased, while the growth of Rothia, a nitrate-reducing bacterium beneficial for blood pressure, was stimulated.Conclusions The use of o-cymen-5-ol and zinc chloride as antimicrobial agents in oral mouthwashes is a valuable alternative to classical antimicrobial agents.

Prolonged standing at work is associated with health risks. The appearance of lower-limb and lower-back discomfort is one of the most prevalent factors in prolonged standing workers. The aim of this research was to evaluate the effect of an eight-hour workday on foot pressure and musculoskeletal discomfort in standing workers. Thirty-six assembly-line workers (six women) were recruited to participate in a cross-sectional study to assess foot pressure and surface, foot, knee, and lower-back discomfort before and after a real workday. Baropodometry outcomes (surface and pressure) were evaluated by the pressure platform SensorMedica and musculoskeletal discomfort was evaluated by Cornell’s Musculoskeletal Discomfort Questionaire. Total foot surface (p = 0.01) and foot discomfort (p = 0.03) increased significantly at the end of the workday. Prolonged standing during 8 h workday increased the foot discomfort and total foot surface in assembly-line workers. No foot pressure variable (forefoot, rearfoot, or total) was significantly modified after the workday in assembly-line workers.

Alphavirus vectors based on self-amplifying RNA (saRNA) generate high and transient levels of transgene expression and induce innate immune responses, making them an interesting tool for antitumor therapy. These vectors are usually delivered as viral particles, but it is also possible to administer them as RNA. We evaluated this possibility by in vivo electroporation of Semliki Forest virus (SFV) saRNA for local treatment of murine colorectal MC38 subcutaneous tumors. Optimization of saRNA electroporation conditions in tumors was performed using an SFV vector coding for luciferase. Then we evaluated the therapeutic potential of this approach using an SFV saRNA coding for interleukin-12 (SFV-IL-12), a proinflammatory cytokine with potent antitumor effects. Delivery of SFV-IL-12 saRNA by electroporation led to improvement in tumor control and higher survival compared with mice treated with electroporation or with SFV-IL-12 saRNA alone. The antitumor efficacy of SFV-IL-12 saRNA electroporation increased by combination with systemic PD-1 blockade. This therapy, which was also validated in a hepatocellular carcinoma tumor model, suggests that local delivery of saRNA by electroporation could be an attractive strategy for cancer immunotherapy. This approach could have easy translation to the clinical practice, especially for percutaneously accessible tumors.

The aim is to investigate the usefulness of lactate dehydrogenase (LDH)/Albumin, LDH/Lymphocyte and LDH/Platelet ratios on the prognosis of coronavirus disease (COVID-19) Alpha (B.1.1.7) variant pneumonia.

Peribacaları, vadileri, mağaraları, yer altı şehirleri vemanastırları ile ünlü Kapadokya, her yıl birçok turisttarafından ziyaret edilmektedir. Ziyaretçiler sadece tarihive doğal güzellikler için değil, sosyal ve kültüreletkinlikler için de Kapadokya bölgesini tercihetmektedirler. Bölgede faaliyet gösteren turizmişletmeleri; konaklama, yeme-içme, eğlence vb. hizmetlerisunmakta bununla birlikte bölge kongre, fuar ve festivalgibi çeşitli etkinliklere de ev sahipliği yapmaktadır.Bu çalışma ile dünya çapında üne sahip KapadokyaBölgesi’nin kongre turizm potansiyelinin belirlenmesiamaçlanmaktadır. Bu amaç doğrultusunda çalışmadaSWOT analizi tercih edilmiştir. Çalışmada öncelikleulusal ve uluslararası literatürden yararlanılarak kongreturizmi kavramsal çerçevede ele alınmış, sonrasında veritoplama aracı olarak SWOT analizine uygun bir anketformu hazırlanmıştır. Veriler Kapadokya bölgesindefaaliyet gösteren 18 işletme yöneticisi, bölge ile ilgiliçalışmaları bulunan 15 akademisyen, turizm eğitimi alan20 lisansüstü öğrencisi ve Kapadokya bölgesindekongreye katılan 10 katılımcının hazırlanan anketsorularına vermiş olduğu cevaplardan derlenmiştir.Sonuçlar elde edilen verilerin aritmetik ortalamasıalınarak hazırlanan tablolar ile analiz edilmiştir. Yapılananaliz sonucuna göre ilgili kişi ve kuruluşlar için gerekliöneriler sunulmuştur.

Abstract Delirium after surgery or Postoperative delirium (POD) is an underdiagnosed entity, despite its severity and high incidence. Patients with delirium require a longer hospital stay and present more postoperative complications, which also increases hospital costs. Given its importance and the lack of specific treatment, multifactorial preventive strategies are evidenced based. Our hypothesis is that using general anaesthesia and avoiding the maximum time in excessively deep anaesthetic planes through BIS neuromonitoring device will reduce the incidence of postoperative delirium in patients over the age of 65 and their hospitalization stay. Patients were randomly assigned to two groups: The visible BIS group and the hidden BIS neuromonitoring group. In the visible BIS group, the depth of anaesthesia was sustained between 40 and 60, while in the other group the depth of anaesthesia was guided by hemodynamic parameters and the Minimum Alveolar Concentration value. Patients were assessed three times a day by research staff fully trained during the 72 h after the surgery to determine the presence of POD, and there was follow-up at 30 days. Patients who developed delirium (n = 69) was significantly lower in the visible BIS group (n = 27; 39.1%) than in the hidden BIS group (n = 42, 60.9%; p = 0.043). There were no differences between the subtypes of delirium in the two groups. Patients in the hidden BIS group were kept for 26.6 ± 14.0 min in BIS values

The site Zamostje 2, located in Sergiev-Posad district of Moscow (Russia) on the west bank of the Dubna River, has provided two Mesolithic and one Early Neolithic occupations dated from 7000 to 5400 cal BC. Thanks to the waterlogged environment, the site has an exceptional preservation. The site has yielded fishing screens, fishing fences, wooden fishing traps, and several small cordage remains elaborated with plant fibres, pine bark floats, fragments of paddles, and other wooden objects. In this work, we present the study of the fragments of cordage and fishing nets with the objective of providing new insights into the production and use of implements made of plant fibres. We have characterized the production process by analysing the morphological and technical characteristics by carrying out experimentation with plant fibres in order to obtain reference material to recognize them at an archaeological level. The analysis of 82 knots and 23 fragments of strings has allowed to determine that they were elaborated with single threads from 0.5 to 1.5 mm thick, which is noticeably smaller than most examples from other sites. All of them were elaborated with woody bast fibres.

The main objective in this study was to determine the prevalence of Chronic Kidney Disease (CKD) in people with Type 2 Diabetes Mellitus (T2DM) in the Autonomous Community (AC) of Aragon (Spain) and to detect whether or not there is under-registration in the patient's history. As a secundary objetive, it was proposed to study the most relevant demographic and clinical characteristics of people with CKD. Observational and retrospective real world data study of the population over 18 years of age with a diagnosis of T2DM, between January 2017 and December 2021. A descriptive analysis of qualitative and quantitative variables, and a comparison using the parametric Student's t-test or the non-parametric Mann-Whitney U-test between both groups was performed. The prevalence of T2DM was 8.07 % and that of CKD 31.4 %, with an under-reporting of 47 %. The main risk factor associated with CKD was arterial hypertension (p<0.001), followed by dyslipidemia (p<0.001). The main treatment used for diabetes control was metformin, both in patients with and without CKD (p<0.001). A total of 56.81 % of people with T2DM and CKD did not undergo annual monitoring of their renal function (glomerular filtration rate) or determination of albuminuria. The prevalence of CKD increases in patients with T2DM (31.4 %), and in almost half of patients the diagnosis is not registered (47 %). This under-reporting delays the implementation of measures needed to prevent CKD progression. • We analyze the presence of CKD (chronic kidney disease) in people with diabetes. • Using big data of 90,700 diabetic patients, analyzing their CKD under-registration. • 31.4 % diabetic patients exhibit CKD, and 47 % of these cases are undiagnosed. • The primary risk factors associated with CKD are hypertension and dyslipidemia. • 56.8 % diabetic subjects with CKD did not undergo annual monitoring of their renal function. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The thiol-disulphide (TDH) homeostasis was investigated in a number of disorders. The aim of the present study is to investigate the dynamic thiol-disulphide homeostasis in patients diagnosed with obstructive jaundice and to compare the dynamic thiol-disulphide homeostasis with ischemia-modified albumin. METHODS: A total of 146 participants who were admitted to the emergency department and who consisted of 69 patients and 77 healthy volunteers were included in the study. Detailed blood samples were obtained from the patients at the time of admission. Thiol/disulphide levels were examined using a brand-new method developed by Erel and Neselioglu on the patients diagnosed with obstructive jaundice during the admission. Data were evaluated in the computer system. RESULTS: The levels of total thiol (p =0.025) and native thiol (p =0.023) were statistically significantly lower in the patient with obstructive jaundice than in the control group. It was observed that there was a significant negative correlation between the native thiol levels and the ALP (r =-0.262, p

The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/bicarbonate anion exchanger 2 (Ae2), with 4,4’-diisothiocyanatostilbene-2,2’-disulfonicacid (DIDS) enhancedCD4+ andCD8+ T cell function upon TCR activation in vitro, especially under low pH conditions. In vivo, DIDS administration delayed B16OVA tumor growth in immunocompetent mice as monotherapy or when combined with adoptive T cell transfer of OVA-specificT cells. Notably, genetic Ae2 silencing in OVA-specificT cells improvedCD4+/CD8+ T cell function in vitro as well as their antitumor activity in vivo. Similarly, genetic modification of OVA-specificT cells to overexpress Hvcn1, a selectiveH+ outward current mediator that prevents cell acidification, significantly improved T cell function in vitro, even at low pH conditions. The adoptive transfer of OVA-specificT cells overexpressing Hvcn1 exerted a better antitumor activity in B16OVA tumor-bearingmice. Hvcn1 overexpression also improved the antitumor activity of CAR T cells specific for Glypican 3 (GPC3) in mice bearing PM299L-GPC3tumors. Our results suggest that preventing intracellular acidification by regulating the expression of acidifier ion channels such as Ae2 or alkalinizer channels like Hvcn1 in tumor-specificlymphocytes enhances their antitumor response by making them more resistant to the acidic TME.

Herein, we report the nanofiltration performance of poly(p-xylylene) thin films with imidazole side chains that were deposited onto commercial polyethersulfone ultrafiltration membranes using a chemical vapor deposition process. The resulting thin films with a few tens of nanometers exhibited water permeation under a pressure difference of 0.5 MPa and selectively rejected water-soluble organic dyes based on their molecular sizes. Additionally, thin flaky ZIF-L crystals (Zn(mim)2·(Hmim)1/2·(H2O)3/2) (Hmim = 2-methylimidazole) formed on the surface of imidazole-containing poly(p-xylylene) films, and the composite films demonstrated the ability to adsorb methylene blue molecules within the cavities of ZIF-L.

Background One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, even though they are not expressed by the tumor cells. We have generated a CAR specific for the splice variant extra domain A (EDA) of fibronectin, which is highly expressed in the tumor stroma of many types of tumors but not in healthy tissues.Methods EDA expression was explored in RNA-seq data from different human tumor types and by immunohistochemistry in paraffin-embedded tumor biopsies. Murine and human anti-EDA CAR-T cells were prepared using recombinant retro/lentiviruses, respectively. The functionality of EDA CAR-T cells was measured in vitro in response to antigen stimulation. The antitumor activity of EDA CAR-T cells was measured in vivo in C57BL/6 mice challenged with PM299L-EDA hepatocarcinoma cell line, in 129Sv mice-bearing F9 teratocarcinoma and in NSG mice injected with the human hepatocarcinoma cell line PLC.Results EDA CAR-T cells recognized and killed EDA-expressing tumor cell lines in vitro and rejected EDA-expressing tumors in immunocompetent mice. Notably, EDA CAR-T cells showed an antitumor effect in mice injected with EDA-negative tumor cells lines when the tumor stroma or the basement membrane of tumor endothelial cells express EDA. Thus, EDA CAR-T administration delayed tumor growth in immunocompetent 129Sv mice challenged with teratocarcinoma cell line F9. EDA CAR-T treatment exerted an antiangiogenic effect and significantly reduced gene signatures associated with epithelial-mesenchymal transition, collagen synthesis, extracellular matrix organization as well as IL-6-STAT5 and KRAS pathways. Importantly, the human version of EDA CAR, that includes the human 41BB and CD3ζ endodomains, exerted strong antitumor activity in NSG mice challenged with the human hepatocarcinoma cell line PLC, which expresses EDA in the tumor stroma and the endothelial vasculature. EDA CAR-T cells exhibited a tropism for EDA-expressing tumor tissue and no toxicity was observed in tumor bearing or in healthy mice.Conclusions These results suggest that targeting the tumor-specific fibronectin splice variant EDA with CAR-T cells is feasible and offers a therapeutic option that is applicable to different types of cancer.

Mycobacteria, like other microorganisms, survive under different environmental variations by expressing an efficient adaptive response, oriented by regulatory elements, such as transcriptional repressors of the TetR family. These repressors in mycobacteria also appear to be related to cholesterol metabolism. In this study, we have evaluated the effect of a fatty acid (oleic–palmitic–stearic)/cholesterol mixture on some phenotypic and genotypic characteristics of a tetR-mutant strain (BCG_2177c mutated gene) of M. bovis BCG, a homologous of Rv2160A of M. tuberculosis. In order to accomplish this, we have analyzed the global gene expression of this strain by RNA-seq and evaluated its neutral-lipid storage capacity and potential to infect macrophages. We have also determined the macrophage response by measuring some pro- and anti-inflammatory cytokine expressions. In comparison with wild-type microorganisms, we showed that the mutation in the BCG_2177c gene did not affect the growth of M. bovis BCG in the presence of lipids but it probably modified the structure/composition of its cell envelope. Compared to with dextrose, an overexpression of the transcriptome of the wild-type and mutant strains was observed when these mycobacteria were cultured in lipids, mainly at the exponential phase. Twelve putative intracellular redox balance maintenance genes and four others coding for putative transcriptional factors (including WhiB6 and three TetR-like) were the main elements repeatedly overexpressed when cultured in the presence of lipids. These genes belonged to the central part of what we called the “genetic lipid signature” for M. bovis BCG. We have also found that all these mycobacteria genotypic changes affected the outcome of BCG-infected macrophages, being the mutant strain most adapted to persist longer inside the host. This high persistence result was also confirmed when mutant-infected macrophages showed overexpression of the anti-inflammatory cytokine TGF-β versus pro-inflammatory cytokines. In summary, the lack of this TetR-like repressor expression, within a lipid environment, may help mycobacteria overcome intracellular redox stress and survive longer inside their host.

The purpose of the present study was to examine the visual perception system in expert climbers through a psychophysical optical test in a cross-sectional study. Twenty-seven male participants with an International Rock Climbing Research Association (IRCRA) best on-sight lead skill level ranging between 18 and 27 and a best red-point level ranging between 18 and 29 completed a series of psychophysical optic tests assessing their visual field, visual acuity, and contrast sensitivity. Climbers were divided by their best red-pointed lead level, and, following IRCRA recommendations, two groups were created: an advanced group (IRCRA redpoint level between 18 and 23), and an elite-high elite group (IRCRA redpoint level between 24 and 29). The elite group presented more training days per week (5.25 ± 1.28), best on-sighted lead level (24.63 ± 1.92 IRCRA), and best red-pointed lead level (26.63 ± 2.56 IRCRA) than the advanced group (3.67 ± 0.91 training days per week, 19.50 ± 1.04 IRCRA on-sighted level and 20.67 ± 1.57 IRCRA red-pointed level). Better visual perception outputs were produced by the group of elite climbers in visual field tests; no differences were observed between the two groups for visual acuity and contrast sensitivity tests. Overall, findings indicate that best climbers performed better at the visual perception tasks that tested their visual field. Such better perception from best climbers is discussed given (1) the greater time they spend coercing the visual system during practicing climbing and (2) the specific complexity of the stimuli as they are confronted to harder routes where holds are less perceptible and the time to find best hold sequences is constrained.