Nontuberculous Mycobacteria Isolates in Respiratory Samples and Mycobacterial Pulmonary Disease in an Area of Northern Spain.

Introduction: The epidemiology of nontuberculous mycobacteria (NTM) is not well known. In this study, we aimed to determine the incidence of NTM isolates and nontuberculous mycobacterial pulmonary disease (NTM-PD) in five closely located hospitals in an area of northern Spain and analyse differences between them. Material and methods: Demographic, microbiological, clinical and radiological data were collected retrospectively from all patients with a NTM isolated from respiratory specimens at five hospitals between 2012 and 2019. Mycobacterium gordonae isolates were excluded. Once the data was collected, it was determined which patients met the NMT-PD criteria. Results: 594 patients were included in the study. The mean incidence rate of NTM isolates across all five hospitals in the period studied was 4.15 per 100,000 person-year, while the rate of NTM-PD was 1.2. The annual number of isolates showed an upward trend over this period, but the same did not occur in the number of cases of NTM-PD. The species most frequently isolated were Mycobacterium avium complex (MAC) and Mycobacterium xenopi and those most frequently causing disease were MAC and Mycobacterium kansassi. There were significant differences between the five centres. Conclusions: Our results are in line with similar studies in Europe in terms of NTM isolation and NTM-PD incidence and species isolated; however, we do not see the upward trend in NTM-PD rates described elsewhere. The great variability in isolation and disease rates, as well as in species isolated in geographically close areas, underlines, in our opinion, the importance of local environmental factors.

Introducción: La epidemiología de las micobacterias no tuberculosas (MNT) no se conoce bien. Nuestro objetivo fue determinar la incidencia de aislamientos de MNT y de enfermedad pulmonar por micobacterias no tuberculosas (EP-MNT) en cinco hospitales del norte de España, próximos entre sí, y analizar las diferencias entre ellos. Material y métodos: Se recopilaron retrospectivamente datos demográficos, microbiológicos, clínicos y radiológicos de todos los pacientes con una MNT aislada en muestra respiratoria entre 2012 y 2019 en los cinco hospitales. Se excluyeron los aislamientos de Mycobacterium gordonae. Una vez recogidos los datos, se determinó qué casos cumplían los criterios de EP-MNT. Resultados: Se incluyeron 594 pacientes. La tasa de incidencia media de aislamientos de NTM en los cinco hospitales fue de 4,15 por 100.000 personas-año y la tasa de EP-MNT fue de 1,2. El número anual de aislamientos mostró una tendencia creciente durante este periodo, pero no así el de EP-MNT. Las especies aisladas con mayor frecuencia fueron Mycobacterium avium complex (MAC) y Mycobacterium xenopi y las que causaron enfermedad con mayor frecuencia fueron MAC y Mycobacterium kansasii. Hubo diferencias significativas entre los cinco centros. Conclusiones: Nuestros resultados están en línea con estudios similares en Europa en términos de aislamiento de MNT, incidencia de EP-MNT y especies aisladas; sin embargo, no vemos la tendencia ascendente en las tasas de EP-MNT descrita en otros lugares. La gran variabilidad entre los cinco hospitales en las tasas de aislamiento y de enfermedad y en las especies aisladas resalta la importancia de los factores ambientales locales.

Quantum Effects Explain the Twist Angle in the Helical Structure of DNA.

Why are DNA bases stacked in a double helix structure? We combined three theoretical approaches to demonstrate how one core concept derived from quantum mechanics (Pauli repulsion) annihilates the contribution of dispersion to the π-π stacking. The helical architecture is governed by a combination of exchange and electrostatic forces, a result that is interpreted from both a computational and a biological perspective.

CSF1R Ligands Expressed by Murine Gliomas Promote M-MDSCs to Suppress CD8+ T Cells in a NOS-Dependent Manner.

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma-secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in the M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that is driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

Validation of a Clinical Scale for Early Detection of Infections at the Exit Site of Central Venous Catheters for Hemodialysis.

Introduction: Exit-site infections (ESI) of central venous catheters for hemodialysis (CVC-HD) has been associated with early catheter removal and an increased risk of CVC-HD related bacteremia. No specific clinical scales to predict ESI have previously been validated. Methods: A multicenter prospective cohort study was performed to validate the proposed scale, which is based on the following 5 signs and symptoms: (i) pain at exit site during interdialytic period; (ii) hyperemia or erythema ≥2 cm from exit site; (iii) inflammation, induration, or swelling at exit site; (iv) fever ≥38 °C not attributable to other causes, and (v) obvious abscess or purulent exudate at the exit site. Adult patients with a tunneled CVC-HD for at least 1 month after insertion has been included. During each hemodialysis session, the exit site was assessed with the proposed scale by nurses. If any item was present, a pericatheter skin swab culture was collected: positive results were gold standard. The scale was validated using receiver operating characteristic (ROC) curves and logistic regression analysis. For this purpose, the logit function was applied, and the ESI probability calculated, as elogit ESI/1 + elogit ESI. Results: Three hundred thirty-seven CVC-HDs from 310 patients were analyzed, producing 515 cultures (117 infected and 398 healthy). The final version of the scale includes the following 3 signs and symptoms, which present the greatest predictive capacity: (i) pain at exit site during interdialytic period, (ii) hyperemia or erythema ≥2 cm from exit site, and (iii) abscess or purulent exudate at the exit site. The final version generated an area under the ROC curve (AUC) of 88.3% (95% confidence interval [CI]: 85.2%-91%; P < 0.001), Youden index 0.7557 ≈ 1, sensitivity 80.34% (95% CI: 71.36%-87.71%) and specificity 95.23% (95% CI: 92.73%-97%). Conclusions: The validation shows that the scale has good predictive properties, detecting approximately 90% of ESI with very acceptable validity parameters.

"Wait, Do I Need More Fiber?" Exploring UK Consumers' Dietary Fiber-Related Awareness and White Bread as a Viable Solution to Promote Subsequent Intake.

Background: Sufficient dietary fiber consumption is associated with well-established health benefits, yet such intake is currently suboptimal globally. Thus, there is interest in developing strategies to improve dietary fiber intake. One such approach is to increase the dietary fiber content of staple foods, but this needs relevant investigation. Methods: Forty-two United Kingdom (UK) based consumers (18-76 y) were recruited to take part in seven focus group sessions investigating: (i) key factors in food choice; (ii) dietary fiber-related knowledge, awareness, consumption habits, and engagement levels; (iii) willingness to consume dietary fiber-rich staple foods; and (iv) gain initial feedback on dietary fiber-rich breads. Results: Overall, key dietary fiber themes emerged such as knowledge (benefits, foods, recommendations and labeling), consumption (not measuring intake), barriers (convenience and knowledge), resources (education and public appeal), and topics (food examples and cooking). Consumers were positive per se to the idea of dietary fiber-rich staple foods but with various caveats (no changes in appearance, taste, and cost). White bread trends were centered around context (sandwich and toast), habit (comfort food), preferences (soft and fresh), and consumption is variable (daily to less often). In addition, consumers' preferred labeling strategy for dietary fiber-rich breads was predominately focused on transparency and visibility. Overall, the newly developed breads were well received demonstrating the potential of our prototypes to fit into the white bread market; however, additional consumer insights are needed. Conclusion: Our findings recommend combining education with a personalized element of advice, coupled with a collective effort from the government and food industry, as essential to help encourage a step-change in dietary fiber consumption in the UK population.

Systemically targeting monocytic myeloid-derived suppressor cells using dendrimers and their cell-level biodistribution kinetics.

The focus of nanoparticles in vivo trafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalities in vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.

Introducing electron correlation in solid-state calculations for superconducting states.

Analyzing the electronic localization of superconductors has been recently shown to be relevant for understanding their critical temperature [Nature Communications, 12, 5381, (2021)]. However, these relationships have only been shown at the Kohn-Sham density functional theory (DFT) level, where the onset of strong correlation linked to the superconducting state is missing. In this contribution, we approximate the superconducting gap in order to reconstruct the superconducting the one-reduced density matrix (1RDM) from a DFT calculation. This allows us to analyse the electron density and localization in the strong correlation regime. The method is applied to two well-known superconductors. Electron localization features along the electron-phonon coupling directions and hydrogen cluster formations are observed for different solids. However, in both cases we see that the overall localization channels are not affected by the onset of superconductivity, explaining the ability of DFT localization channels to characterize the superconducting ones.

Prevalence of Diamine Oxidase Enzyme (DAO) Deficiency in Subjects with Insomnia-Related Symptoms.

Background: To assess the prevalence of diamine oxidase (DAO) enzyme deficiency caused by single nucleotide polymorphisms (SNPs) of the AOC1 gene in a sample of patients with symptoms of insomnia. Methods: A total of 167 adult patients (>18 years of age) with symptoms of insomnia attended a specialized institute for healthy sleep, in Barcelona (Spain), between May and November 2023, and underwent genotyping analysis of the four most relevant SNP variants, including c.691G>7 (rs2052129), c.47C>T (rs10156191), c.995C>T (rs1049742), and c.1990C>G (rs1049793). Results: Genetic DAO deficiency was present in 138 patients, with a prevalence rate of 82.6% (95% CI 76-88.1%). Difficulties in staying asleep were the most common complaints in 88% of patients followed by trouble falling asleep in 60.5%. More than half of patients suffered from insomnia symptoms every day. Also, 99.4% reported daytime consequences of insomnia, with fatigue (79.6%), mood changes (72.5%), and impaired concentration in 70.1%. When patients were grouped by DAO-score, which reflected the number of heterozygous and homozygous SNPs variants, the group with a DAO-score ≥ 4 vs. 1 showed higher percentages of insomnia-related symptoms, in particular, trouble staying asleep and early morning awakening. These two symptoms were also more common in the presence of the c.1990C>G (rs1049793) variant. Conclusions: This preliminary real-world study presents novel evidence of a potential link between a DAO enzyme deficiency of a genetic origin and clinical symptoms of insomnia, which may suggest the potential benefit of DAO supplementation to improve the quality of sleep in these subjects. The study was registered at ClinicalTrials.gov (NCT06488027).

Predictors of Hospital Readmission, Institutionalization, and Mortality in Geriatric Rehabilitation Following Hospitalization According to Admission Reason.

BACKGROUND AND PURPOSE: Older adults following an inpatient geriatric rehabilitation (GR) program commonly experience adverse health outcomes such as hospital readmission, institutionalization, and mortality. Although several studies have explored factors related to these outcomes, the influence of admission reason on the predictive factors of adverse health outcomes in the rehabilitation process remains unclear. Therefore, this study aimed to identify predictive factors for adverse health outcomes in inpatients attending GR according to their admission reason. METHODS: This retrospective study included patients with orthogeriatric (OG) conditions and patients with hospital-associated deconditioning (HAD) admitted to GR after an acute hospitalization between 2016 and 2020. Patients were evaluated by a comprehensive geriatric assessment at admission, including sociodemographic data, social resources, clinical data, cognitive, functional and nutritional status, and physical performance measurements. Adverse health outcomes were collected (hospital readmission, institutionalization, and mortality). Univariate analyses and multivariate backward binary logistic regressions were used to determine predictive factors. RESULTS AND DISCUSSION: In this study, 290 patients were admitted for OG conditions, and 122 patients were admitted due to HAD. In patients with OG conditions, lower Mini-Mental State Examination (MMSE) predicted institutionalization and mortality. Lower Mini Nutritional Assessment-Short Form predicted institutionalization, whereas lower Barthel Index and lower Tinetti-Performance-Oriented Mobility Assessment scores were associated with higher mortality. In patients with HAD, higher age-adjusted comorbidity index predicted hospital readmission and mortality, and lower Short Physical Performance Battery scores predicted institutionalization and mortality. Finally, lower MMSE scores, worse values in Older Americans Resources and Services Scale and male gender were associated with a higher risk of institutionalization. CONCLUSIONS: Predictive factors for hospital readmission, institutionalization, and mortality in patients with OG conditions and HAD during GR were different. Some of those predictors, such as nutritional status and physical performance, are modifiable. Understanding predictive factors for adverse outcomes, and how these factors differ by admission diagnosis, improves our ability to identify patients most at risk. Early identification of these patients could assist with prevention efforts and lead to a reduction of negative outcomes.

Leveraging sensor-based functional outcomes to enhance understanding of the patient experience: challenges and opportunities.

INTRODUCTION: Sensor-based digital health technology (DHT) has emerged as a promising means to assess patient functioning within and outside clinical trials. Sensor-based functional outcomes (SBFOs) provide valuable insights that complement other measures of how a patient feels or functions to enhance understanding of the patient experience to inform medical product development. AREAS COVERED: This perspective paper provides recommendations for defining SBFOs, discusses the core evidence required to support SBFOs to inform decision-making, and considers future directions for the field. EXPERT COMMENTARY: The clinical outcome assessment (COA) development process provides an important starting point for developing patient-centered SBFOs; however, given the infancy of the field, SBFO development may benefit from a hybrid approach to evidence generation by merging exploratory data analysis with patient engagement in measure development. Effective SBFO development requires combining unique expertise in patient engagement, measurement and regulatory science, and digital health and analytics. Challenges specific to SBFO development include identifying concepts of interest, ensuring measurement of meaningful aspects of health, and identifying thresholds for meaningful change. SBFOs are complementary to other COAs and, as part of an integrated evidence strategy, offer great promise in fostering a holistic understanding of patient experience and treatment benefits, particularly in real-world settings.

Glioma-derived M-CSF and IL-34 license M-MDSCs to suppress CD8+ T cells in a NOS-dependent manner.

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that are driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

Serum biomarkers for liver fibrosis assessment.

Liver fibrosis is the result of chronic liver injury of different etiologies produced by an imbalance between the synthesis and degeneration of the extracellular matrix and dysregulation of physiological mechanisms. Liver has a high regenerative capacity in the early stage of chronic diseases so a prompt liver fibrosis detection is important. Consequently, an easy and economic tool that could identify patients with liver fibrosis at the initial stages is needed. To achieve this, many non-invasive serum direct, such as hyaluronic acid or metalloproteases, and indirect biomarkers have been proposed to evaluate liver fibrosis. Also, there have been developed formulas that combine these biomarkers, some of them also introduce clinical and/or demographic parameters, like FIB-4, non-alcoholic fatty liver disease fibrosis score (NFS), enhance liver fibrosis (ELF) or Hepamet fibrosis score (HFS). In this manuscript we critically reviewed different serum biomarkers and formulas for their utility in the diagnosis and progression of liver fibrosis.

Videoconference-Supervised Group Exercise Reduces Low Back Pain in Eldercare Workers: Results from the ReViEEW Randomised Controlled Trial.

PURPOSE: To assess the effects of a group exercise intervention conducted by real-time videoconference on the low back pain of eldercare workers. METHODS: We randomly assigned 130 eldercare workers to an experimental group (EG: n = 65) or control group (CG: n = 65). Participants from both groups took part in routine prevention programs carried out in their workplace, and participants from the EG received an additional 12-week resistance-exercise intervention supervised by real-time videoconference. Assessments were conducted before and after the intervention, and the primary outcome was average low back pain intensity during the last 7 days, measured by the 0-10 numerical rating scale. Secondary outcomes included additional measures of low back, neck, shoulder and hand/wrist pain, as well as psycho-affective parameters, medication consumption and muscle performance. Both intention-to-treat and per-protocol analyses were applied with a group-by-time ANCOVA including baseline measurements as covariates. RESULTS: 125 participants completed post-intervention assessments (EG: n = 63, CG: n = 62). The intention-to-treat analysis showed an effect favouring the EG on average low back pain intensity (p = 0.034). Improvements in additional low back and hand/wrist pain outcomes were also observed, as well as on upper limb muscle performance (p < 0.05). The per-protocol analysis demonstrated additional benefits in depression, quality of life, hypnotic/anxiolytic medication consumption and lower limb and trunk muscle performance in participants with ≥ 50% adherence (p < 0.05). CONCLUSIONS: The intervention was effective for reducing the low back and hand/wrist pain of eldercare workers and increasing upper limb muscle performance. The per-protocol analysis showed additional benefits in psycho-affective parameters, medication consumption and muscle performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05050526. Registered 20 September 2021-Prospectively registered, https://www. CLINICALTRIALS: gov/study/NCT05050526.

Evaluation of measured and calculated small dense low-density lipoprotein in capillary blood and association with the metabolic syndrome.

BACKGROUND AND AIMS: Small-dense-low-density-lipoprotein cholesterol (sdLDL-C) is proatherogenic and not commonly measured. The aims were to evaluate capillary blood and its stability for sdLDL-C measurement and measure sdLDL-C in patients with metabolic syndrome (MS). METHODS: 182 patients were studied (49 with MS). sdLDL-C was measured by electrophoresis (LipoPrint®), direct measurement (Roche Diagnostics) and Sampson equation. Intima-media thickness (IMT) and presence of atheroma was evaluated. sdLDL-C was compared in paired venous and capillary blood according to CLSI-EP09c (n = 40). sdLDL-C stability was studied after 24 h at room temperature (RT). RESULTS: sdLDL-C in capillary blood and venous blood showed agreement with the direct measurement (bias: 4.17 mg/dL, LOA 95 %:-5.66; 13.99) and estimation (bias:8.12 mg/dL, LOA 95 %:-8.59; 24.82). sdLDL-C is stable in capillary blood for 24 h at RT. The electrophoretic method yielded lower (p < 0.05) sdLDL-C than the equation or direct measurement. Patients with MS had (p < 0.05) higher sdLDL-C (%) than patients without MS. Patients with atheroma plaques had higher sdLDL-C (p < 0.05). Estimated sdLDL-C correlated with IMT (r = 0.259, p < 0.001). CONCLUSIONS: Capillary blood is an alternative to venous blood for sdLDL-C measurement and is stable for 24 h after collection. Estimated and directly measured sdLDL-C associate with the MS being accessible tools for cardiovascular risk assessment.

Human values, civic participation, and wellbeing: analysis on their relationship among older Europeans.

Introduction: So far, both for the general and older population, research on human values and wellbeing mainly shows correlational associations but does not inquire about the direction of this relationship. This is also true for values and civic participation. Therefore, our objective is to identify the directional association between civic participation and Schwartz values, and between values and wellbeing, among older Europeans. Methods: A pseudo-panel was created from the cross-sectional data of the European Social Survey (ESS 2002-2018), controlling for gender, age-group, country and level of studies (n = 3926). The data analysis was performed using a cross-lagged model, applying both random-effects and fixed-effects models. Results: On the one hand, the relationship between participation and values is bidirectional, but the effect of civic participation on values is more significant since participating stimulates the development of certain values. On the other hand, although the relationship between values and wellbeing is also bidirectional, the effect of wellbeing on values is stronger since a given level of wellbeing favors the development of particular values. Discussion: We conclude that civic participation should be promoted within the older population since it directly increases wellbeing, and moreover reinforces those (Growth-oriented) values that positively influence the health, happiness and life satisfaction of older people.

Relevance of comorbidities for main outcomes during different periods of the COVID-19 pandemic.

Background: Throughout the evolution of the COVID-19 pandemic, the severity of the disease has varied. The aim of this study was to determine how patients' comorbidities affected and were related to, different outcomes during this time. Methods: Retrospective cohort study of all patients testing positive for SARS-CoV-2 infection between March 1, 2020, and January 9, 2022. We extracted sociodemographic, basal comorbidities, prescribed treatments, COVID-19 vaccination data, and outcomes such as death and admission to hospital and intensive care unit (ICU) during the different periods of the pandemic. We used logistic regression to quantify the effect of each covariate in each outcome variable and a random forest algorithm to select the most relevant comorbidities. Results: Predictors of death included having dementia, heart failure, kidney disease, or cancer, while arterial hypertension, diabetes, ischemic heart, cerebrovascular, peripheral vascular diseases, and leukemia were also relevant. Heart failure, dementia, kidney disease, diabetes, and cancer were predictors of adverse evolution (death or ICU admission) with arterial hypertension, ischemic heart, cerebrovascular, peripheral vascular diseases, and leukemia also relevant. Arterial hypertension, heart failure, diabetes, kidney, ischemic heart diseases, and cancer were predictors of hospitalization, while dyslipidemia and respiratory, cerebrovascular, and peripheral vascular diseases were also relevant. Conclusions: Preexisting comorbidities such as dementia, cardiovascular and renal diseases, and cancers were those most related to adverse outcomes. Of particular note were the discrepancies between predictors of adverse outcomes and predictors of hospitalization and the fact that patients with dementia had a lower probability of being admitted in the first wave.

Prognostic value of neutrophil-to-lymphocyte ratio at diagnosis in colorectal cancer: propensity score analysis.

INTRODUCTION: baseline neutrophil-to-lymphocyte ratio (NLR) at the time of colorectal cancer (CRC) diagnosis has been proposed as a predictor of long-term survival. The aim of this study was to analyze its usefulness in a homogeneous population with control of the main confounding factors. METHODOLOGY: observational study of 836 patients who underwent surgery for CRC. Patients were divided into two groups: NLR ≤ 3.3 vs NLR > 3.3. To control for confounders, they were matched one-to-one by propensity analysis. A final cohort of 526 patients was included in the study. RESULTS: the two groups were mismatched in terms of age, comorbidity, tumor stage, rectal location, and neoadjuvant therapy. Once matching was performed, baseline NLR was statistically significantly associated with long-term survival (p < 0.001) and behaved as an independent prognostic factor for survival (p = 0.001; HR: 1.99; 95 % CI: 1.32-3.00) when adjusted in a Cox regression model using age (p < 0.001; HR: 1.04; 95 % CI: 1.02-1.06) and the Charlson Comorbidity Index (p < 0.001; HR: 1.40; 95 % CI: 1.27-1.55). Neoadjuvant therapy lost its statistical significance (p = 0.137; HR: 1.59; 95 % CI: 0.86-2.93). CONCLUSIONS: a high baseline NLR (> 3.3) in patients with colorectal cancer at diagnosis represents a poor prognostic factor in terms of survival. Its use in routine practice could intensify therapeutic strategies and follow-up in these patients.

Self-perception of natural outcome, appearance, and emotional well-being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender.

BACKGROUND: OnabotulinumtoxinA (onabotA) is indicated for upper facial lines (UFL). Fear of unnatural-looking outcomes is a frequently reported treatment barrier. AIMS: Examine patient-reported outcomes (PROs) after onabotA treatment for UFL. METHODS: A post hoc analysis was conducted on two 12-month pivotal studies of onabotA for forehead and glabellar lines (20 U each), with/without treatment of crow's feet lines (±24 U). This analysis used PROs from the Facial Line Satisfaction Questionnaire: Items 4 (natural look), 5 (treatment effect), 11 (met expectations), and Impact Domain (appearance and psychological impact). The analysis included 458 neurotoxin-naive adults achieving a ≥2-grade improvement in forehead line (FHL) severity on the Facial Wrinkle Scale at Day 30 (primary endpoint). [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'forehead line (FHL)' in this version.] Data were further stratified into millennials and men. RESULTS: At Day 30, 90.5% of all participants, 94.6% of millennials, and 85.7% of men were satisfied with receiving a natural look. Millennials had higher odds of being satisfied with natural outcomes at Day 30. This measure remained > 80% for all groups throughout the 12 months. Additionally, ≥80% were satisfied with the treatment effect, and >90% reported results met expectations. At Day 30, ≥50% reported positive impacts on self-perceived appearance and psychological well-being, but millennials had higher, and men had lower odds of reporting these improvements. CONCLUSIONS: Participants achieving a ≥2-grade improvement in FHL severity after onabotA reported high satisfaction with natural outcomes and the treatment effect, with improved self-perceived appearance and psychological well-being. [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'FHL' in this version.] These results may help aesthetic providers and patients address fears regarding unnatural results with onabotA.

Molecular insight into endosulfan degradation by Ese protein from Arthrobacter: Evidence-based structural bioinformatics and quantum mechanical calculations.

Endosulfan is an organochlorine insecticide widely used for agricultural pest control. Many nations worldwide have restricted or completely banned it due to its extreme toxicity to fish and aquatic invertebrates. Arthrobacter sp. strain KW has the ability to degrade α, ß endosulfan and its intermediate metabolite endosulfate; this degradation is associated with Ese protein, a two-component flavin-dependent monooxygenase (TC-FDM). Employing in silico tools, we obtained the 3D model of Ese protein, and our results suggest that it belongs to the Luciferase Like Monooxygenase family (LLM). Docking studies showed that the residues V59, V315, D316, and T335 interact with α-endosulfan. The residues: V59, T60, V315, D316, and T335 are implicated in the interacting site with ß-endosulfan, and the residues: H17, V315, D316, T335, N364, and Q363 participate in the interaction with endosulfate. Topological analysis of the electron density by means of the Quantum Theory of Atoms in Molecules (QTAIM) and the Non-Covalent Interaction (NCI) index reveals that the Ese-ligands complexes are formed mainly by dispersive forces, where Cl atoms have a predominant role. As Ese is a monooxygenase member, we predict the homodimer formation. However, enzymatic studies must be developed to investigate the Ese protein's enzymatic and catalytic activity.