The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.

A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.

Factors influencing the health-related quality of life of older men and women living with HIV in Spain.

The number of older people living with HIV (OPLHIV) is increasing worldwide. However, little is known about the factors that better predict their health-related quality of life (HRQoL). We administered the validated WHOQoL-HIV BREF questionnaire to 247 Spanish OPLHIV (192 men and 55 women). In addition to the six domains of the questionnaire, we constructed a seventh domain as theaverage of punctuations of all domains. Multivariable Poisson regression models with robust estimates by sex were constructed for the seven domains (14 in total). The best-subset selection method together with Mallow's Cp metric was used to select the model factors. The percentage of variability explained by Poisson models ranged from15-38% for men and 29-70% for women. The analysis showed that women were most affected by ageing (four domains), mobility impairments (five domains), and mental disorders (five domains). The factors with the greatest negative influence on men were heterosexuality (six domains), mental disorders (six domains), being single (five domains), and poverty risk (three domains). Physical activity was found to improve HRQoL in both men (six domains) and women (four domains). Future OPLHIV programmes would benefit from considering sex specific HRQoL factors. This could also improve the cost-effectiveness of interventions.

Circulating Immune Proteins: Improving the Diagnosis and Clinical Outcome in Advanced Non-Small Cell Lung Cancer.

Immunotherapy has been proven a viable treatment option for non-small cell lung cancer (NSCLC) treatment in patients. However, some patients still do not benefit. Finding new predictive biomarkers for immunocheckpoint inhibitor (ICI) response will improve treatment management in the clinical routine. In this regard, liquid biopsy is a useful and noninvasive alternative to surgical biopsies. In the present study, we evaluated the potential diagnostic, prognostic, and predictive value of seven different soluble mediators involved in immunoregulation. Fifty-two plasma samples from advanced NSCLC treated in first-line with pembrolizumab at baseline (PRE) and at first response assessment (FR) were analyzed. In terms of diagnostic value, our results revealed that sFGL1, sGAL-3, and sGAL-1 allowed for optimal diagnostic efficacy for cancer patients. Additionally, the combination of sFGL1 and sGAL-3 significantly improved diagnostic accuracy. Regarding the predictive value to assess patients' immune response, sCD276 levels at PRE were significantly higher in patients without tumor response (p = 0.035). Moreover, we observed that high levels of sMICB at PRE were associated with absence of clinical benefit (pembrolizumab treatment less than 6 months) (p = 0.049), and high levels of sMICB and sGAL-3 at FR are also related to a lack of clinical benefit (p = 0.027 and p = 0.03, respectively). Finally, in relation to prognosis significance, at PRE and FR, sMICB levels above the 75th percentile are related to poor progression-free survival (PFS) (p = 0.013 and p = 0.023, respectively) and overall survival (OS) (p = 0.001 and p = 0.011, respectively). An increase in sGAL3 levels at FR was associated with worse PFS (p = 0.037). Interestingly, high sGAL-3 at PRE was independently associated with PFS and OS with a hazard ratio (HR) of 2.45 (95% CI 1.14-5.25; p = 0.021) and 4.915 (95% CI 1.89-12.73; p = 0.001). In conclusion, plasma levels of sFGL1, sGAL-3, and sGAL-1 could serve as diagnostic indicators and sMICB, sCD276, and sGAL3 were linked to outcomes, suggesting their potential in assessing NSCLC under pembrolizumab treatment. Our results highlight the value of employing soluble immune biomarkers in advanced lung cancer patients treated with pembrolizumab at first-line.

Impact of Penicillin Allergy Label on Length of Stay and Mortality in Hospitalized Patients through a Clinical Administrative National Dataset.

BACKGROUND: Penicillin allergy is a common problem in the management of infectious diseases. The aim of this study was to determine the impact of penicillin allergy on length of hospital stay (LOHS) among hospitalized adult patients and on in-hospital mortality at a national level. METHODS: A retrospective cohort study of adult patients discharged from the Spanish Hospital System between 2006 and 2015 was conducted using the Minimum Basic Data Set (MBDS). We compared LOHS and in-hospital mortality of adult patients whose records contained penicillin allergy code V14.0 (International Classification of Diseases, Ninth Revision, Clinical Modification) as a secondary diagnosis, with a random sample without such a code. RESULTS: We identified 981,291 admissions with code V14.0, which corresponded to 2.63% of all hospitalizations. Adults patients with a penicillin allergy label were significantly older than patients without such a label, with a median of 70 years (interquartile range [IQR]: 51-80) versus 63 years (IQR: 40-77). The proportion of women and the prevalence of infectious diseases were higher in the group with a penicillin allergy label (61.40% vs. 53.84%; 34.04% vs. 30.01%; respectively). We found a higher median Elixhauser-Van Walraven score in hospitalized patients with an allergy label. The median LOHS for hospitalizations with a penicillin allergy label (5 [IQR: 2-9]) was significantly longer than that in those without such a label (4 [IQR: 2-9]). Multivariate analysis showed an increase in LOHS due to the penicillin allergy label (odds ratio [OR] [95% confidence interval [CI]: 1.061 [1.057-1.065]) and a decrease in mortality in penicillin allergy records (OR [95% CI]: 0.834 [0.825-0.844]). CONCLUSION: In our study, the prevalence of a penicillin allergy label in hospitalized patients, using the MBDS, is low. Hospitalizations with an allergy label was associated with a longer LOHS. However, penicillin-allergic patients did not show higher mortality rates. Inaccurate reporting of penicillin allergies may have an impact on healthcare resources.

Does mitomycin-C concentration have any influence on XEN45 gel stent outcomes in a real-world setting?

BACKGROUND: To compare the effectiveness and safety of XEN45 implanted with mitomycin-C (MMC) 0.01% versus (vs) XEN45 implanted with MMC 0.02%. METHODS: Retrospective and single-center study conducted on consecutive patients with open-angle glaucoma or ocular hypertension who underwent XEN45-implant, either alone or in combination with cataract surgery. The primary end-point was the mean change in intraocular pressure (IOP) from baseline to the last follow-up visit. RESULTS: Fifty-five patients (63 eyes) were included. Thirty-seven (58.7%) eyes underwent surgery with MMC 0.01% and 26 (41.3%) ones with MMC 0.02%. In the overall study sample, the mean (standard error) IOP was significantly lowered from 17.6 (0.7) mm Hg at baseline to 12.6 (0.3) mm Hg at month 12. The IOP was significantly lowered from 17.3 (15.4 to 19.2) mm Hg and 17.9 (16.1 to 17.8) mm Hg at baseline to 12.3 (11.3 to 13.3) mm Hg and 13.1 (12.3 to 13.9) mm Hg at month 12 in the MMC 0.01% and MMC 0.02% groups, respectively; p < 0.0001 each. The mean number of ocular-hypotensive medications significantly decreased from 2.1 (1.9 to 2.3) at baseline to 0.2 (0.04 to 0.3) at month 12, p < 0.0001, with no significant differences between MMC 0.01% and MMC 0.02% groups, p = 0.5181. At month 12, 50 (80.6%) eyes had functioning blebs. Regarding safety, 18 (28.6%) eyes have experience adverse events. CONCLUSION: XEN45, either alone or in combination with cataract surgery, showed a good effectiveness and safety profile. MMC dose had no influence on the IOP lowering, which may support the use of the lowest dose.

A systematic review of possible airborne transmission of the COVID-19 virus (SARS-CoV-2) in the indoor air environment.

At the end of December 2019, the rapid spread of the COVID-19 (SARS-CoV-2) disease and, subsequently, deaths around the world, lead to the declaration of the pandemic situation in the world. At the beginning of the epidemic, much attention is paid to person-to-person transmission, disinfection of virus-contaminated surfaces, and social distancing. However, there is much debate about the routes of disease transmission, including airborne transmission, so it is important to elucidate the exact route of transmission of the COVID-19 disease. To this end, the first systematic review study was conducted to comprehensively search all databases to collect studies on airborne transmission of SARS-CoV-2 in indoor air environments. In total, 14 relevant and eligible studies were included. Based on the findings, there is a great possibility of airborne transmission of SARS-CoV-2 in indoor air environments. Therefore, some procedures are presented such as improving ventilation, especially in hospitals and crowded places, and observing the interpersonal distance of more than 2 m so that experts in indoor air quality consider them to improve the indoor air environments. Finally, in addition to the recommendations of the centers and official authorities such as hand washing and observing social distancing, the route of air transmission should also be considered to further protect health personnel, patients in hospitals, and the public in other Public Buildings.

Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components.

BACKGROUND: Metabolic syndrome (MetS) prevalence in rheumatoid arthritis (RA) patients is known to vary considerably across the world. This study aimed to determine the prevalence of MetS in RA patients from western Mexico and to analyze the interrelation of the MetS components with the clinical variables of RA. METHODS: This case-control study included 216 RA patients and 260 control subjects (CS). MetS prevalence was determined according to the NCEP/ATP III and the Latin American Consensus of the Latin American Diabetes Association (ALAD) criteria. RESULTS: MetS was observed in 30.6% RA patients and 33.3% of controls (p > 0.05) according to NCEP/ATP III and 28.7% in RA patients and 31.1% for controls using ALAD criteria. Total cholesterol, LDL-C, and Castelli's I-II indexes were lower in RA (p < 0.001) than in CS. The RA patients with MetS had more swollen joints than those without MetS (p = 0.018). In RA patients with MetS, DAS-28 score correlated with smoking index (rho = 0.4601, p = 0.0004) and VLDL-C (rho = 0.3108, p = 0.0056); similarly, rheumatoid factor (RF) correlated with age (rho = 0.2031, p = 0.0027), smoking index (rho = 0.3404, p < 0.0001), triglycerides (rho = 0.1958, p = 0.0039), and VLDL-C (rho = 0.1761, p = 0.0162). CONCLUSIONS: The MetS prevalence in RA patients from western Mexico is not higher than controls; however, in RA patients with MetS, some inflammatory markers are associated with MetS components; thus, the control of MetS in RA could be beneficial to regulate disease activity.

Chlorpyrifos remediation in agriculture runoff with homogeneous solar photo-Fenton reaction at near neutral pH: phytotoxicity assessment.

This study represents the first application of Fe-citrate-based photo-Fenton chemistry for the degradation of chlorpyrifos (CPF) spiked into agricultural runoff, and its phytotoxicity assessment. The effects of the initial CPF concentration, time and ratio of Fe-citrate/H2O2 on CPF removal during the photo-Fenton reaction were investigated and modeled with analysis of variance using R software by the response-surface methodology package. According to the stationary point in original units, the optimal condition for 70.00% CPF removal was as follows: CPF = 2.5 mg L-1 (0.0), time = 48.0 min (0.585) and Fe-citrate/H2O2 = 0.075 (0.539). Beside running the system at near-neutral pH, another strength of this study is related to the treatment of agricultural runoff contaminated with CPF with a raceway pond reactor, which has the advantages of simplicity of the facilities and procedures, as well as the possibility of using sunlight more efficiently in the field of applications. Finally, untreated and treated agriculture runoffs were used as irrigation to determine their phytotoxic effects on seed germination of cress (Lepidium sativum). Solar photo-Fenton treatment greatly reduced phytotoxicity of agriculture runoff and showed the highest germination percentage (70%) compared to both raw agricultural runoff (60%) and untreated CPF-spiked runoff (35%).

Environmental exposure to nonylphenol and cancer progression Risk-A systematic review.

Environmental exposure to nonylphenol (NP) can adversely affect human and wildlife health. A systematic review was conducted to evaluate the relationship between environmental NP exposure and cancer progression risk. Literature surveys were conducted within several international databases using appropriate keywords. A comprehensive search yielded 58 eligible studies involving a wide range of adverse effects, exposure assessment methods, study designs, and experimental models. Most studies reported that NP strongly induced breast cancer progression in intended experiments. Positive associations between NP exposure and ovarian, uterine, pituitary, and testicular cancers were also reported. Although some studies reported no relation between environmental NP exposure and tumour and/or cancer progression, NP (a known endocrine disrupting chemical) induced action mechanisms in multiple experimental models and may interfere with/hyper-activate oestrogen signalling. Secretion of oestrogen and development of reproductive tissues like breasts, uteruses, and ovaries showed strong associations with possible neoplasia (i.e., uncontrolled development of tumours and/or malignant cancers). Findings of this study are important for informing policymakers to pass legislation limiting the use of environmental contaminants such as NP before all adverse effects of exposure have been determined.

Reintubation in the ICU following cardiac surgery: is it more difficult than first-time intubation in the operating room?: A prospective observational study.

BACKGROUND: After cardiac surgery, a patient's trachea is usually extubated; however, 2 to 13% of cardiac surgery patients require reintubation in the ICU. OBJECTIVE: The objective of this study was to compare the initial intubation in the cardiac operating room with reintubation (if required) in the ICU following cardiac surgery. DESIGN: A prospective, observational study. SETTING: Department of Anesthesiology and Intensive Care Medicine, Clinical Hospital of Santiago, Spain. PATIENTS: With approval of the local ethics committee, over a 44-month period, we prospectively enrolled all cardiac surgical patients who were intubated in the operating room using direct laryngoscopy, and who required reintubation later in the ICU. MAIN OUTCOME MEASURES: The primary endpoint was to compare first-time success rates for intubation in the operating room and ICU. Secondary endpoints were to compare the technical difficulties of intubation (modified Cormack-Lehane glottic view, operator-reported difficulty of intubation, need for support devices for direct laryngoscopy) and the incidence of complications. RESULTS: A total of 122 cardiac surgical patients required reintubation in the ICU. Reintubation was associated with a lower first-time success rate than in the operating room (88.5 vs. 97.6%, P = 0.0048). Reintubation in the ICU was associated with a higher incidence of Cormack-Lehane grades IIb, III or IV views (34.5 vs. 10.7%, P < 0.0001), a higher incidence of moderate or difficult intubation (17.2 vs. 6.5%, P = 0.0001) and a greater need for additional support during direct laryngoscopy (20.5 vs. 10.7%, P = 0.005). Complications were more common during reintubations in the ICU (39.3 vs. 5.7%, P < 0.0001). CONCLUSION: Compared with intubations in the operating room, reintubation of cardiac surgical patients in the ICU was associated with more technical difficulties and a higher incidence of complications. CLINICAL TRIAL NUMBER: Ethics committee of Galicia number 2015-012.

Microglia Play an Active Role in Obesity-Associated Cognitive Decline.

Obesity affects >600 million people worldwide, a staggering number that appears to be on the rise. One of the lesser known consequences of obesity is its deleterious effects on cognition, which have been well documented across many cognitive domains and age groups. To investigate the cellular mechanisms that underlie obesity-associated cognitive decline, we used diet-induced obesity in male mice and found memory impairments along with reductions in dendritic spines, sites of excitatory synapses, increases in the activation of microglia, the brain's resident immune cells, and increases in synaptic profiles within microglia, in the hippocampus, a brain region linked to cognition. We found that partial knockdown of the receptor for fractalkine, a chemokine that can serve as a "find me" cue for microglia, prevented microglial activation and cognitive decline induced by obesity. Furthermore, we found that pharmacological inhibition of microglial activation in obese mice was associated with prevention of both dendritic spine loss and cognitive degradation. Finally, we observed that pharmacological blockade of microglial phagocytosis lessened obesity-associated cognitive decline. These findings suggest that microglia play an active role in obesity-associated cognitive decline by phagocytosis of synapses that are important for optimal function.SIGNIFICANCE STATEMENT Obesity in humans correlates with reduced cognitive function. To investigate the cellular mechanisms underlying this, we used diet-induced obesity in mice and found impaired performance on cognitive tests of hippocampal function. These deficits were accompanied by reduced numbers of dendritic spines, increased microglial activation, and increased synaptic profiles within microglia. Inhibition of microglial activation by transgenic and pharmacological methods prevented cognitive decline and dendritic spine loss in obese mice. Moreover, pharmacological inhibition of the phagocytic activity of microglia was also sufficient to prevent cognitive degradation. This work suggests that microglia may be responsible for obesity-associated cognitive decline and dendritic spine loss.

The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol.

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.

The effects of living in an outdoor enclosure on hippocampal plasticity and anxiety-like behavior in response to nematode infection.

The hippocampus of rodents undergoes structural remodeling throughout adulthood, including the addition of new neurons. Adult neurogenesis is sensitive to environmental enrichment and stress. Microglia, the brain's resident immune cells, are involved in adult neurogenesis by engulfing dying new neurons. While previous studies using laboratory environmental enrichment have investigated alterations in brain structure and function, they do not provide an adequate reflection of living in the wild, in which stress and environmental instability are common. Here, we compared mice living in standard laboratory settings to mice living in outdoor enclosures to assess the complex interactions among environment, gut infection, and hippocampal plasticity. We infected mice with parasitic worms and studied their effects on adult neurogenesis, microglia, and functions associated with the hippocampus, including cognition and anxiety regulation. We found an increase in immature neuron numbers of mice living in outdoor enclosures regardless of infection. While outdoor living prevented increases in microglial reactivity induced by infection in both the dorsal and ventral hippocampus, outdoor mice with infection had fewer microglia and microglial processes in the ventral hippocampus. We observed no differences in cognitive performance on the hippocampus-dependent object location task between infected and uninfected mice living in either setting. However, we found that infection caused an increase in anxiety-like behavior in the open field test but only in outdoor mice. These findings suggest that living conditions, as well as gut infection, interact to produce complex effects on brain structure and function.

Response surface methodology modeling to improve degradation of Chlorpyrifos in agriculture runoff using TiO2 solar photocatalytic in a raceway pond reactor.

This paper deals with the use of a raceway pond reactor (RPR) as an alternative photoreactor for solar photocatalytic applications. Raceway pond reactors are common low-cost reactors which can treat large volumes of water. The experiments were carried out with TiO2 in the agriculture effluent spiked with Chlorpyrifos (CPF) at circumneutral pH. The Response Surface Methodology (RSM) was used to find the optimum process parameters to maximize CPF oxidation from the mathematical model equations developed in this study using R software. By ANOVA, p-value of lack of fit > 0.05 indicated that, the equation was well-fitted. The theoretical efficiency of CPF removal, under the optimum oxidation conditions with UV solar energy of around 697 ± 5.33 lux, was 84.01%, which is in close agreement with the mean experimental value (80 ± 1.42%) confirming that the response model was suitable for the optimization. As far as the authors know, this is the first study of CPF removal using RPR in agriculture runoff at circumneutral pH.

Modelling of Behavior for Inhibition Corrosion of Bronze Using Artificial Neural Network (ANN).

In this work, three models based on Artificial Neural Network (ANN) were developed to describe the behavior for the inhibition corrosion of bronze in 3.5% NaCl + 0.1 M Na2SO4, using the experimental data of Electrochemical Impedance Spectroscopy (EIS). The database was divided into training, validation, and test sets randomly. The parameters process used as the inputs of the ANN models were frequency, temperature, and inhibitor concentration. The outputs for each ANN model and the components in the EIS spectrum (Zre, Zim, and Zmod) were predicted. The transfer functions used for the learning process were the hyperbolic tangent sigmoid in the hidden layer and linear in the output layer, while the Levenberg-Marquardt algorithm was applied to determine the optimum values of the weights and biases. The statistical analysis of the results revealed that ANN models for Zre, Zim, and Zmod can successfully predict the inhibition corrosion behavior of bronze in different conditions, where what was considered included variability in temperature, frequency, and inhibitor concentration. In addition, these three input parameters were keys to describe the behavior according to a sensitivity analysis.

[PERSIRIS study: observational study, postmarketing, prospective, to evaluate the persistence to treatment with monthly risedronate in women with osteoporosis]. / Estudio PERSIRIS: estudio observacional, postautorización, prospectivo, para evaluar la persistencia al tratamiento con risedronato mensual en mujeres con osteoporosis.

OBJECTIVE: To assess the persistence of treatment with monthly risedronate and know the reasons of persistence and nontherapeutic persistence and the profile of the non-persistent patients. DESING: Observational, postmarketin and prospective study. LOCATION: Primary care, traumatology, rheumatology, gynecology and geriatrics of Catalonia. PARTICIPANTS: Women with osteoporosis treated with monthly risedronate that previously had abandoned weekly bisphosphonate therapy. MAIN MEASUREMENTS: Percentage of patients on persistent monthly risedronate year of their prescription, reasons for persistent and non persistent and profile of non persistent patients in relation to biodemographic data, clinical data and risk factors for fracture. RESULTS: 289 evaluable patients with a mean age of 68.3. At 12 months of initiation with monthly risedronate, 58.1% of patients remained on treatment. Most frequent reasons for leaving: fear of having side effects and belief that the disease is typical of the age. Reasons remarkable persistence: comfort/ease and dosage. Significant differences were observed between persistent and non-persistent patients relative to: employment status, number of concomitant therapy and height; however the results of possible associated factors must be contextualized within the study characteristics and the difference in size does not seem clinically relevant. CONCLUSIONS: The administration of therapeutic patterns more comfortable as monthly risedronate in osteoporosis, could facilitate persistence in patients improving the effectiveness of the drug. However in that persistence can also influence biodemographic and clinical variables and diverse of various kinds.

Healthcare program for sex workers: a public health priority.

OBJECTIVE: The objective of this study was to propose a model of health care for sexual workers (SWs) and transvestites (Ts) groups who were historically excluded from health services. MATERIALS AND METHODS: A prospective descriptive/analytical study with an intervention stage was performed, focusing on the health status of SWs and Ts. Access to health system, inclusion into social programs, beneficiaries' participation, and rate of risk behaviors were variables measured before and after intervention that consist in a program based on promotion/prevention activities and complete health care service suitable to SW-T needs. RESULTS: Nine hundred and fifty SW-Ts were included. At baseline, 99.7% lacked health insurance and 90.1% had no access to the health care. These data were compared with those obtained after attention quadruplicated among SW because of the implementation of the program. Risky sexual behaviors were reduced by 25 times. SWs have their own leader of health institutions and coordinate themselves with the program's activities. CONCLUSION: Responsibility of the state's authorities on vulnerable groups must focus on their inclusion. To this end, health services must adapt themselves in order to attend those community groups with special needs. Active participation of the target population contributes to viability of this type of proposals, and it is essential for the project's success.

Sex differences in health-related quality of life and poverty risk among older people living with HIV in Spain: A cross-sectional study.

BACKGROUND: Current antiretroviral therapies have increased the life expectancy of people living with HIV (PLHIV). There is, however, limited evidence regarding the health-related quality of life (HRQoL) and living conditions of older people living with HIV (OPLHIV) in Spain. METHODS: We implemented a self-administered online questionnaire to identify sex differences in HRQoL and poverty risk among Spanish OPLHIV (PLHIV ≥50 years). Participants were contacted through non-governmental organisations. We used the standardised WHOQoL-HIV BREF questionnaire and the Europe 2020 guidelines to estimate HRQoL and poverty risk respectively. The statistical analysis included multivariable generalised linear models with potential confounding variables and robust estimates. RESULTS: The study included 247 OPLHIV (192 men and 55 women). On the WHOQoL-HIV BREF questionnaire, men scored higher on 84% of items and in all six domains. Women had significantly lower HRQoL in five domains: physical health (ß: -1.5; 95% CI: -2.5, -0.5; p: 0.002), psychological health (ß: -1.0; 95% CI: -1.9, -0.1; p: 0.036), level of independence (ß: -1.1; 95% CI: -1.9, -0.2; p: 0.019), environmental health (ß: -1.1; 95% CI: -1.8, -0.3; p: 0.008), and spirituality/personal beliefs (ß: -1.4; 95% CI: -2.5, -0.3; p: 0.012). No statistical differences were found in the domain of social relations. Poverty risk was considerable for both men (30%) and women (53%), but women were significantly more likely to experience it (OR: 2.9; 95% CI: 1.3, 6.5; p: 0.009). CONCLUSION: The aging of PLHIV is a public health concern. Our findings indicate that HRQoL and poverty risk among Spanish OPLHIV differ significantly by sex. Spain should, therefore, implement specific policies and interventions to address OPLHIV needs. The strategies must place a high priority on the reduction of sex inequalities in HRQoL and the enhancement of the structural conditions in which OPLHIV live.

Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.

BACKGROUND: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. OBJECTIVE: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. METHODS: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. RESULTS: ARR decreased from 1.9 (95% confidence interval 1.60-2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17-0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13-0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18-0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. CONCLUSIONS: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.

Soluble galectin-3 as a microenvironment-relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma.

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin-3 (GAL-3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non-small cell lung cancer patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early-stage patients and commercial cell lines were cultured, using tumorsphere-forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL-3 using reverse transcription-quantitative real-time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry, and immunoassay analysis. Our results using three-dimensional (3D) models of lung tumor cells revealed that soluble GAL-3 (sGAL-3) is highly expressed and secreted. To more accurately mimic the TME, a co-culture of tumorspheres and fibroblasts was used, revealing that GAL-3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (TREGS ). In the translational phase, we confirmed that patients with high expression levels of GAL-3 had more TREGS , which suggests that tumors may be recruiting this population through GAL-3. Next, we evaluated levels of sGAL-3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL-3 could be used as an independent prognostic biomarker for overall survival and relapse-free survival in early-stage LUAD patients. Additionally, levels of sGAL-3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first-line pembrolizumab were evaluated, further supporting that sGAL-3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve of 0.801 (P = 0.011). Moreover, high levels might predict decreased progression-free survival and OS to anti-PD-1 therapy, with sGAL-3 being a prognosis-independent biomarker for advanced LUAD.