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In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3+ cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161+ T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161+ T cells; upregulation of CD69 was observed on both CD161− and CD161+ T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN- γ but no IL-4, IL-5 and IL-13 by CD161+ T cells in all groups; upon polyclonal stimulation, there were more CD161+ T cells producing IFN- γ and less CD161− T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161+ T cells are activated and are able to produce predominantly IFN- γ but no Th2 cytokines. We hypothesize that during an asthma attack, IFN- γ produced by CD161+ T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks. [ABSTRACT FROM AUTHOR]

Background: The yeast Saccharomyces cerevisiae, commonly used in industry, exhibits complex metabolism due to the Crabtree effect, fermenting alcohol even under aerobic conditions when glucose exceeds 0.10-0.15 g/L. The heat released by the biological activity is a signal very easy to collect, given the minimal instrumentation requirements. However, this heat depends on the activated metabolic pathways and provides only an indirect indicator, that cannot be used in a simple way. This study demonstrated the potential of a mechanistic model to control the process by measuring the heat released by the biological activity., Results: The complexity arising from coexisting metabolic pathways was addressed by a comprehensive model of Saccharomyces cerevisiae together with the heat of reaction included in a rigorous enthalpy balance of the bioreactor. Batch cultures were performed in an insulated bioreactor to trigger a temperature signal. The heat of individual metabolic pathways was determined by inverse analysis of these tests using Particle Swarm Optimization (PSO): -101.28 ±0.02kJ/mol for anaerobic fermentation, -231.27±0.06kJ/mol for aerobic fermentation, and -662.94 ± 0.54kJ/mol for ethanol respiration. Finally, the model was successfully applied and validated for online training under different operating conditions., Conclusions: The model demonstrates remarkable accuracy, with a mean relative error under 0.38% in temperature predictions for both anaerobic and aerobic conditions. The viscous dissipation is a key parameter specific to the bioreactor and the growth conditions. However, we demonstrated that this parameter could be fitted accurately from the early stages of the experiment for further prediction of the remaining part. This model introduces temperature, or the thermal power required to maintain temperature, as a measurable parameter for online feedback model training to provide increasingly precise feed-forward control., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Endometriosis is a chronic gynecological disease associated with chronic debilitating pain, poor mental health and quality of life. The objective of this paper is to evaluate the effectiveness of psychological interventions aimed at improving the pain, quality of life and mental health of women with endometriosis., Methods: A systematic review (SR) of the literature with meta-analysis (MA) was carried out. MEDLINE, Embase, PsycINFO and CENTRAL were searched to locate Randomized Controlled Trials (RCTs). The risk of bias assessment of each study was conducted using the Cochrane Collaboration's RoB 2.0 tool., Results: Seven RCTs were included ( N  = 757). The data obtained suggest that psychological interventions reduce dyspareunia [standardized mean difference (SMD): -0.54, 95% CI: -0.86, -0.22] and dyschezia [mean difference (MD): -2.90, 95% CI: -4.55, -1.26] and increase mental health levels (SMD: 0.70, 95% CI: 0. 42, 0.99); they also point to a large reduction in levels of trait anxiety (MD: -6.63, 95% CI: -8.27, -4.99) and depression (MD: -2.49, 95% CI: -3.20, -1.79), and a likely reduction in state anxiety (MD: -9.72, 95% CI: -13.11, -6.33) experienced by women with endometriosis. It was also identified that psychological interventions probably slightly reduce pelvic pain and may increase physical health. However, most of the included studies have a high overall risk of bias or have certain concerns, which limit conclusions about the certainty of the evidence., Discussion: The available evidence indicates that psychological interventions are effective in improving the pain, quality of life and mental health variables of women with endometriosis., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42024516100., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 del Pino-Sedeño, Cabrera-Maroto, Abrante-Luis, González-Hernández and Ortíz Herrera.)

This paper reviews the key building blocks needed to develop a mechanistic model for use as an operational production tool. The Chinese Hamster Ovary (CHO) cell, one of the most widely used hosts for antibody production in the pharmaceutical industry, is considered as a case study. CHO cell metabolism is characterized by two main phases, exponential growth followed by a stationary phase with strong protein production. This process presents an appropriate degree of complexity to outline the modeling strategy. The paper is organized into four main steps: (1) CHO systems and data collection; (2) metabolic analysis; (3) formulation of the mathematical model; and finally, (4) numerical solution, calibration, and validation. The overall approach can build a predictive model of target variables. According to the literature, one of the main current modeling challenges lies in understanding and predicting the spontaneous metabolic shift. Possible candidates for the trigger of the metabolic shift include the concentration of lactate and carbon dioxide. In our opinion, ammonium, which is also an inhibiting product, should be further investigated. Finally, the expected progress in the emerging field of hybrid modeling, which combines the best of mechanistic modeling and machine learning, is presented as a fascinating breakthrough. Note that the modeling strategy discussed here is a general framework that can be applied to any bioprocess., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Current evidence reveals concerning rates of non-adherence to antidepressant treatment, possibly influenced by various relevant determinants such as sociodemographic factors or those related to the health system and their professionals. The aim of this paper is to review the scientific evidence on sociodemographic and clinical predictors of adherence to pharmacological treatment in patients diagnosed with a depressive disorder. Methods: a systematic review (SR) was conducted. The search for a previous SR was updated and de novo searches were performed in Medline, EMBASE, Web of Science (WoS) and PsycInfo (last 10 years). The risk of bias was assessed using the Cochrane tool for non-randomized studies-of Exposure (ROBINS-E). Meta-analyses were conducted. Results: Thirty-nine studies ( n = 2,778,313) were included, 24 of them in the meta-analyses. In the initiation phase, no association of adherence was found with any of the predictors studied. In the implementation and discontinuation phases, middle-aged and older patients had better adherence rates and lower discontinuation rates than younger ones. White patients adhered to treatment better than African-American patients. Discussion: Age and ethnicity are presented as the predictive factors of pharmacological adherence. However, more research is needed in this field to obtain more conclusive results on other possible factors. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023414059], identifier [CRD42023414059]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Del Pino-Sedeño, Infante-Ventura, Hernández-González, González-Hernández, González de León, Rivero-Santana, Hurtado and Acosta Artiles.)

Background: Percutaneous ethanol injection (PEI) has been shown to be a valuable treatment for thyroid nodular pathology and metastatic cervical adenopathies., Objective: To evaluate the effectiveness, safety, and cost-effectiveness of PEI in thyroid nodular pathology and metastatic cervical adenopathies., Methods: A systematic review (SR) using meta-analysis was conducted on the effectiveness and safety of PEI. A SR on cost-effectiveness was also performed. The SRs were conducted according to the methodology developed by the Cochrane Collaboration with reporting in accordance with the PRISMA statement. A cost-minimization analysis was carried out using a decision tree model. Assuming equal effectiveness between two minimally invasive techniques (PEI and radiofrequency ablation (RFA)), the model compared the costs of the alternatives with a horizon of six months and from the perspective of the Spanish National Health System., Results: The search identified three RCTs (n=157) that evaluated PEI versus RFA in patients diagnosed with benign thyroid nodules: ninety-six patients with predominantly cystic nodules and sixty-one patients with solid nodules. No evidence was found on other techniques or thyroid nodular pathology. No statistically significant differences were observed between PEI and RFA in volume reduction (%), symptom score, cosmetic score, therapeutic success and major complications. No economic evaluations were identified. The cost-minimization analysis estimated the cost per patient of the PEI procedure at €326 compared to €4781 for RFA, which means an incremental difference of -€4455., Conclusions: There are no differences between PEI and RFA regarding their safety and effectiveness, but the economic evaluation determined that the former option is cheaper., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

This paper presents the characterization of sargassum that reached the shores of eight Dominican beaches in 2021. The analysis of heavy, alkaline and alkaline-earth metals was performed by ICP-OES. Twelve heavy metals were studied, with the highest concentrations corresponding to Fe, As, and Zn. Regarding the alkaline and alkaline-earth metals, the highest concentrations were detected for Ca, K, Na and Mg. The high values of arsenic and alkali and alkaline-earth metal salts do not suggest using these algae in agriculture. It is recommended to carry out arsenic speciation studies to assess whether the form in which it is found is bioavailable for plants and animals. The heavy metal contamination index was determined, which ranged between 0.318 and 3.279. Finally, for the first time in the country, the organic fraction of sargassum was analyzed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Alopecia is one of the most common adverse effects of chemotherapy, having a significant impact on the quality of life of patients who suffer from it. Among the interventions available for its prevention, scalp cooling (SC) is the most widely used. The aim of this study was to assess the efficacy and safety of the use of SC systems during chemotherapy sessions for the prevention or the reduction of the extent of chemotherapy-induced alopecia., Methods: A systematic review of the literature published up to November 2021 was carried out. Randomized clinical trials were selected. The main outcome measure was alopecia (hair loss>50%) during and after chemotherapy treatment. When possible, a quantitative synthesis of the results was performed through meta-analysis using the Stata v.15.0 software. The risk ratio (RR) of the variable alopecia, was estimated using a random effects model following the Mantel-Haenszel method. Statistical heterogeneity of the results was evaluated graphically and through the test of heterogeneity χ 2 and the Higgins I 2 statistic. Sensitivity analyses and subgroup analyses were performed., Results: 13 studies were included, with a total of 832 participants (97.7% women). In most studies, the main chemotherapy treatment applied was anthracyclines or the combination of anthracyclines and taxanes. The results obtained indicate that SC prevents alopecia (loss>50%) by 43% compared to the control group (RR=0.57; 95% CI=0.46 to 0.69; k=9; n=494; I 2 =63.8%). No statistically significant difference was found between the efficacy of automated and non-automated cooling systems (P=0.967). No serious short- or medium-term adverse events related to SC were recorded., Conclusions: The results suggest that scalp cooling contributes to the prevention of chemotherapy-induced alopecia.

Background: Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. Teleneurology (TN) allows neurology to be applied when the doctor and patient are not present in the same place, and sometimes not at the same time. In February 2021, the Spanish Ministry of Health requested a health technology assessment report on the implementation of TN as a complement to face-to-face neurological care., Methods: A scoping review was conducted to answer the question on the ethical, legal, social, organisational, patient (ELSI) and environmental impact of TN. The assessment of these aspects was carried out by adapting the EUnetHTA Core Model 3.0 framework, the criteria established by the Spanish Network of Health Technology Assessment Agencies and the analysis criteria of the European Validate (VALues In Doing Assessments of healthcare TEchnologies) project. Key stakeholders were invited to discuss their concerns about TN in an online meeting. Subsequently, the following electronic databases were consulted from 2016 to 10 June 2021: MEDLINE and EMBASE., Results: 79 studies met the inclusion criteria. This scoping review includes 37 studies related to acceptability and equity, 15 studies developed during COVID and 1 study on environmental aspects. Overall, the reported results reaffirm the necessary complementarity of TN with the usual face-to-face care., Conclusions: This need for complementarity relates to factors such as acceptability, feasibility, risk of dehumanisation and aspects related to privacy and the confidentiality of sensitive data.

Background and Purpose: The aim was to systematically review the effectiveness and safety of telemedicine combined with usual care (in-person visits) compared to usual care for the therapeutic management and follow-up assessment of neurological diseases., Methods: The electronic databases MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched (June 2021). Randomized controlled trials (RCTs) on patients of any age with neurological diseases were considered. Two reviewers screened and abstracted data in duplicate and independently and assessed risk of bias using the Cochrane risk-of-bias tool for randomized trials (RoB 2). When possible, pooled effect estimates were calculated., Results: Of a total of 3018 records initially retrieved, 25 RCTs (n = 2335) were included: 11 (n = 804) on stroke, four (n = 520) on Parkinson's disease, three (n = 110) on multiple sclerosis, two (n = 320) on epilepsy, one (n = 63) on dementia, one (n = 23) on spina bifida, one (n = 40) on migraine, one (n = 22) on cerebral palsy and one (n = 433) on brain damage. Types of telemedicine assessed were online visits (11 studies), tele-rehabilitation (seven studies), telephone calls (three), smartphone apps (two) and online computer software (two). The evidence was quite limited except for stroke. Compared to usual care alone, telemedicine plus usual care was found to improve depressive symptoms, functional status, motor function, executive function, generic quality of life, healthcare utilization and healthy lifestyle in patients in post-stroke follow-up., Conclusions: Well-designed and executed RCTs are needed to confirm our findings on stroke and to have more scientific evidence available for the other neurological diseases., (© 2022 European Academy of Neurology.)

Patients with Mendelian susceptibility to mycobacterial diseases (MSMD) mainly suffer from Mycobacterium and Salmonella infections, which are due to mutations in genes controlling the interleukin (IL)-12/IL-23-dependent IFN-γ production. We performed a molecular diagnosis in two Mexican patients with persistent mycobacterial infections. Patients 1 (P1) and 2 (P2) from two unrelated, non-consanguineous families from two villages near Mexico City developed bacille Calmette-Guérin (BCG) disease secondary to vaccination; patients and their families were studied at the immunological level for production and response to IFN-γ. The β1 subunit of the IL-12 receptor (encoded by the IL12RB1 gene) was not expressed in cells from P1 or P2, or in two siblings of P1. Sequencing of the IL12RB1 gene showed the same point mutation 1791+2 T>G, homozygous in patients and heterozygous in parents. P1 and P2 died at the ages of 4 and 16 years, respectively, with disseminated and uncontrolled BCG disease and with Candida albicans infections in spite of multiple anti-mycobacterial drug treatments. One of P2's siblings also died following disseminated mycobacterial infection secondary to BCG vaccination. These are the first cases in Mexico of patients with BCG disease traced to a mutation in the IL12RB1 gene, with a fatal outcome. Doctors must be alert to the adverse reactions to BCG vaccination and to persistent Mycobacterium infections, and in such cases should investigate possible mutations in the genes of the IL-12/IL-23-IFN-γ axis., (Copyright © 2010 International Society for Infectious Diseases. All rights reserved.)

Predicted members of the HflX subfamily of phosphate-binding-loop guanosine triphosphatases (GTPases) are widely distributed in the bacterial kingdom but remain virtually uncharacterized. In an attempt to understand mechanisms used for regulation of growth and development in the chlamydiae, obligate intracellular and developmentally complex bacteria, we have begun investigations into chlamydial GTPases; we report here what appears to be the first analysis of a HflX family GTPase using a predicted homologue from Chlamydophila pneumoniae. In agreement with phylogenetic predictions for members of this GTPase family, purified recombinant Cp. pneumoniae HflX was specific for guanine nucleotides and exhibited a slow intrinsic GTPase activity when incubated with [gamma-(32)P]GTP. Using HflX-specific monoclonal antibodies, HflX could be detected by Western blotting and high-resolution confocal microscopy throughout the vegetative growth cycle of Cp. pneumoniae and, at early time points, appeared to partly localize to the membrane. Ectopic expression of Cp. pneumoniae HflX in Escherichia coli revealed co-sedimentation of HflX with the E. coli 50S large ribosomal subunit. The results of this work open up some intriguing possibilities for the role of GTPases belonging to this previously uncharacterized family of bacterial GTPases. Ribosome association is a feature shared by other important conserved GTPase families and more detailed investigations will be required to delineate the role of HflX in bacterial ribosome function.

Long term storage of living cells is a central issue in cell biology and medicine. In addition to the cryoprotectant dimethyl sulphoxide (DMSO), foetal bovine serum (FBS) is often added to the freezing medium for the cryoconservation of serum dependent cell lines. FBS, with its high protein content, protects cells against shear forces and gives the medium a desirable osmotic environment with a physiological viscosity. However, the harvesting of FBS is painful for the foetus and should be avoided for ethical reasons. In this work we describe the adaptation of several commonly used cell lines to serum- and protein-free media; however, such cell lines should not be frozen in a conservation medium containing serum. We tested the synthetic surfactant ''Pluronic F68'', known to protect mammalian cells grown in serum-free bioreactors (Papoutsakis, 1991), as an active cryoprotectant. In samples containing 0.1 to 1% Pluronic F68, we found a significant increase in viable cells after thawing. Values up to 115% of starting cell number indicate that the cells proliferate within the first 24 hours after thawing, a property which was not observed in cryoconservation media without Pluronic F68.

The compound RU41740 from Klebsiella pneumoniae, when used as an immunostimulant, improves responses to bacterial and yeast infections in murine models and in human trials. The aim of this study was to determine in vitro, the capacity of RU41740 to stimulate human leukocytes in whole blood. Blood samples from healthy adult donors were incubated with RU41740 for 4 or 24 h and leukocytes were assessed for levels of activation markers and cytokine production by flow cytometry and ELISA. The early activation marker CD69 was induced at 4 h in NK cells > B cells > T cells > monocytes whereas at 24 h CD80 and CD86 levels were augmented on monocytes and IL-12 was induced; HLA-DR levels increased on both B cells and monocytes. The pro-inflammatory cytokines TNF-alpha and IL-6 were produced at 4 h at similar levels to that induced by LPS and monocytes appeared to be a source of TNF-alpha. IFN-gamma, was induced at 5 h just in NK cells. Activation induced by RU41740 was not abolished by polymixin B, ruling out the possible contamination with LPS. These data indicate that RU41740 can impact not only the innate immune responses but potentially enhance adaptive immune responses by up-regulating expression of molecules involved in antigen presentation on antigen presenting cells.

The genotoxic effect of ozone was studied in human leukocytes in vitro, using the single cell gel electrophoresis (SCGE) assay. Cell treatment for 1 h at 37 degrees C with 0.9-5.3 mM O(3) resulted in a dose-dependent increase of DNA damage, comparable to that induced by 4-40 mM of H(2)O(2), used as a positive control. This effect of ozone was reversed by post-treatment incubation of the cells for 45-90 min at 37 degrees C, and prevented by pre-incubation of the cells with catalase (20 microg/ml). These results demonstrate that O(3) induces DNA-damage in primary human leukocytes. The damage is rapidly repaired, and probably mediated by the formation of H(2)O(2).