TB or Not TB: Lung Nocardiosis, a Tuberculosis Mimicker.

Nocardia, a gram-positive bacterium found in soil and water, rarely causes infections in immunocompetent patients. Diagnosing and treating nocardiosis can be challenging due to its infrequency and the similarity of its symptoms to other diseases. We describe the case of a middle-aged male with a history of latent tuberculosis who presented with hemoptysis. Imaging revealed a persistent lung mass, and pathology and microbiology studies confirmed Nocardia infection. The patient was treated with antibiotics and discharged home. Pulmonary nocardiosis can mimic tuberculosis, fungal infections, or malignancies. Immunocompetent patients make up one-third of the cases. Diagnosis can be difficult, as the organism takes time to grow in culture, but molecular techniques and histology can aid in diagnosis. Treatment often involves a six- to 12-month course of trimethoprim-sulfamethoxazole (TMP-SMX). Prompt identification of the etiological agent is essential for effective treatment, especially for immunocompetent patients who may not exhibit typical risk factors.

Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis.

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.

Neurodegeneration Biomarkers in Adult Spinal Muscular Atrophy (SMA) Patients Treated with Nusinersen.

The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months. Using ELISA technology, the levels of total tau, pNF-H, NF-L, sAPPß, Aß40, Aß42, and YKL-40 were evaluated in CSF samples. Additionally, plasma samples were used to measure NF-L and total tau levels using SIMOA technology. SMA patients showed improvements in clinical outcomes after nusinersen treatment, which were statistically significant only in walkers, in RULM (p = 0.04) and HFMSE (p = 0.05) at 24 months. A reduction in sAPPß levels was found after nusinersen treatment, but these levels did not correlate with clinical outcomes. Other neurodegeneration biomarkers (NF-L, pNF-H, total tau, YKL-40, Aß40, and Aß42) were not found consistently changed with nusinersen treatment. The slow progression rate and mild treatment response of adult SMA types 2 and 3 may not lead to detectable changes in common markers of axonal degradation, inflammation, or neurodegeneration, since it does not involve large pools of damaged neurons as observed in pediatric forms. However, changes in biomarkers associated with the APP processing pathway might be linked to treatment administration. Further studies are warranted to better understand these findings.

Sudden Infant Death Syndrome (SIDS): State of the Art and Future Directions.

Sudden infant death syndrome (SIDS) is a type of death that occurs suddenly and without any apparent explanation, affecting infants between 28 days of life and up to a year. Recognition of this entity includes performing an autopsy to determine if there is another explanation for the event and performing both an external and internal examination of the different tissues to search for possible histopathological findings. Despite the relative success of awareness campaigns and the implementation of prevention measures, SIDS still represents one of the leading causes of death among infants worldwide. In addition, although the development of different techniques has made it possible to make significant progress in the characterization of the etiopathogenic mechanisms underlying SIDS, there are still many unknowns to be resolved in this regard and the integrative consideration of this syndrome represents an enormous challenge to face both from a point of view scientific and medical view as humanitarian. For all these reasons, this paper aims to summarize the most relevant current knowledge of SIDS, exploring from the base the characterization and recognition of this condition, its forensic findings, its risk factors, and the main prevention measures to be implemented. Likewise, an attempt will be made to analyze the causes and pathological mechanisms associated with SIDS, as well as potential approaches and future paths that must be followed to reduce the impact of this condition.

Exploring Scaffold Hopping for Novel 2-(Quinolin-4-yloxy)acetamides with Enhanced Antimycobacterial Activity.

Utilizing a scaffold-hopping strategy from the drug candidate telacebec, a novel series of 2-(quinolin-4-yloxy)acetamides was synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (Mtb) growth. These compounds demonstrated potent activity against drug-sensitive and multidrug-resistant strains (MIC ≤ 0.02 µM). Leading compounds were evaluated against a known qcrB resistant strain (T313A), and their loss in activity suggested that the cytochrome bc1 complex is the likely target. Additionally, these structures showed high selectivity regarding mammalian cells (selectivity index > 500) and stability across different aqueous media. Furthermore, some of the synthesized quinolines demonstrated aqueous solubility values that exceeded those of telacebec, while maintaining low rates of metabolism. Finally, a selected compound prevented Mtb growth by more than 1.7 log10 colony forming units in a macrophage model of tuberculosis (TB) infection. These findings validate the proposed design and introduce new 2-(quinolin-4-yloxy)acetamides with potential for development in TB drug discovery campaigns.

Enhancing sense of belonging in nursing student clinical placements to advance learning and identity development.

Clinical placements are considered one of the "hallmarks" of nursing education. In these settings, students can build upon their theoretical learning by applying knowledge, practicing skills, connecting with nurses and other medical professionals, and creating opportunities to work with diverse populations. As a result, students begin to hone their nurse identity, and build confidence and self-esteem. Importantly, the development of a nursing identity through clinical placement work is improved by integrating opportunities that increase belongingness. Campus climate plays a significant role in creating the environment necessary for belongingness to flourish and leads to enhanced student learning. Taking the role of positive campus climate into consideration, this article argues that instructors supervising undergraduate nursing students in clinical learning environments must create inclusive climates for their students to increase positive educational outcomes. Specific recommendations for creating inclusive clinical learning environments are provided.

Mental health among adolescents exposed to social inequality in Latin America and the Caribbean: a scoping review.

Background and objective: Adolescents from Latin America and the Caribbean grow up in a context of social inequality, which diminishes their well-being and leads to impaired emotional-cognitive development. To understand the problem, it is important to synthesize the available research about it. This study aims to explore the knowledge about adolescents' mental health in Latin America and the Caribbean exposed to social inequality. Methods: A systematic scoping review was conducted encompassing a search in five databases (Medline, CINAHL, PsycINFO, Scopus, and LILACS) in June 2022. Articles of various typologies were included without time limit. After two rounds of screening, relevant data were manually extracted and synthesized into self-constructed themes using thematic analysis. Results: Out of 8,825 retrieved records, 42 papers were included in the final review, with a predominance of quantitative approaches. The synthesis revealed two main analytical themes: (a) defining social inequality, wherein intersecting inequalities produce discrimination and determine conditions for social vulnerability; (b) social inequality and mental health, which highlights the association between socio-structural difficulties and emotional problems, amplifying vulnerability to mental ill health and poor mental health care. Conclusion: The scientific evidence reveals that social inequality is related to impaired well-being and mental ill health on the one hand and a lack of access to mental health care on the other hand.

Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Tucker3-PCovR: The Tucker3 principal covariates regression model.

In behavioral research, it is very common to have manage multiple datasets containing information about the same set of individuals, in such a way that one dataset attempts to explain the others. To address this need, in this paper the Tucker3-PCovR model is proposed. This model is a particular case of PCovR models which focuses on the analysis of a three-way data array and a two-way data matrix where the latter plays the explanatory role. The Tucker3-PCovR model reduces the predictors to a few components and predicts the criterion by using these components and, at the same time, the three-way data is fitted by the Tucker3 model. Both the reduction of the predictors and the prediction of the criterion are done simultaneously. An alternating least squares algorithm is proposed to estimate the Tucker3-PCovR model. A biplot representation is presented to facilitate the interpretation of the results. Some applications are made to empirical datasets from the field of psychology.

CLINICAL OUTCOMES OF A TORIC CONTINUOUS RANGE OF VISION PRESBYOPIA-CORRECTING INTRAOCULAR LENS.

PURPOSE: To evaluate the clinical outcomes of the toric version of a presbyopia-correcting intraocular lens (IOL) based on the combination of a diffractive-based extended depth of focus (EDOF) pattern and a diffractive multifocal platform. SETTING: Miranza COI Bilbao, Spain. DESIGN: Prospective case series. METHODS: Thirty-five patients (51-84 years) with corneal astigmatism ranging from 0.75 to 2.19 D undergoing bilateral cataract surgery with implantation of the Synergy™ Toric II IOL (Johnson & Johnson Vision, Jacksonville, Florida, USA) were evaluated during a 3-month follow-up. Visual acuity, refraction, defocus curve, and patient-reported outcomes with the Catquest-9SF questionnaire were analyzed. A vectorial analysis was used to analyze the accuracy of astigmatic correction. RESULTS: Mean 3-month monocular postoperative uncorrected distance, intermediate (80 cm) and near (40 cm) visual acuities were 0.06±0.11, 0.13±0.12, and 0.13±0.09 logMAR, respectively. Mean monocular distance-corrected intermediate (80 cm) and near visual acuity (40 cm) were 0.11±0.12 and 0.10±0.10 logMAR, respectively. Mean binocular defocus curve showed visual acuities of 0.10 logMAR or better for defocus levels from +0.50 to -2.50 D. Residual cylinder was within ±0.50 D in 97.0% of eyes. The surgically induced astigmatism prediction error ranged between -0.49 and 0.50 D, with a mean value of 0.04±0.16 D. Mean absolute IOL rotation was 3.79±2.94º. Significant improvements were found in all Rasch calibrated scores obtained with Catquest-9SF (p<0.001). CONCLUSIONS: The implantation of the toric presbyopia correcting IOL evaluated provides an efficacious astigmatic correction while providing a fully restoration of the visual function across different distances.

Picosecond quantum-classical dynamics reveals that the coexistence of light-induced microbial and animal chromophore rotary motion modulates the isomerization quantum yield of heliorhodopsin.

Rhodopsins are light-responsive proteins forming two vast and evolutionary distinct superfamilies whose functions are invariably triggered by the photoisomerization of a single retinal chromophore. In 2018 a third widespread superfamily of rhodopsins called heliorhodopsins was discovered using functional metagenomics. Heliorhodopsins, with their markedly different structural features with respect to the animal and microbial superfamilies, offer an opportunity to study how evolution has manipulated the chromophore photoisomerization to achieve adaptation. One question is related to the mechanism of such a reaction and how it differs from that of animal and microbial rhodopsins. To address this question, we use hundreds of quantum-classical trajectories to simulate the spectroscopically documented picosecond light-induced dynamics of a heliorhodopsin from the archaea thermoplasmatales archaeon (TaHeR). We show that, consistently with the observations, the trajectories reveal two excited state decay channels. However, inconsistently with previous hypotheses, only one channel is associated with the -C13C14- rotation of microbial rhodopsins while the second channel is characterized by the -C11C12- rotation typical of animal rhodopsins. The fact that such -C11C12- rotation is aborted upon decay and ground state relaxation, explains why illumination of TaHeR only produces the 13-cis isomer with a low quantum efficiency. We argue that the documented lack of regioselectivity in double-bond excited state twisting motion is the result of an "adaptation" that could be completely lost via specific residue substitutions modulating the steric hindrance experienced along the isomerization motion.

Novel Image-Guided Percutaneous Lung Tissue Excision Device With Integrated Sealing of Blood Vessels and Airways: An In Vivo Preclinical Study.

OBJECTIVE: This study evaluated the efficacy of the Minimally Invasive Targeted Resection (MiTR) device, a novel electrosurgical instrument that allows for targeted excision of a lung abnormality while using bipolar radiofrequency (RF) energy to seal blood vessels and airways. METHODS: The MiTR system was evaluated in 7 acute and 2 chronic porcine (7-day) models to evaluate the efficacy of tissue excision with bipolar RF sealing of blood vessels and airways and application of an autologous blood patch into the excised tissue cavity. Air leak was recorded for all evaluations. The study was approved by the institutional ethical board. RESULTS: Nineteen lung tissue samples, measuring 2.5 cm long × 1.2 cm diameter, were excised. In 8 of 9 animals (89%), hemostasis and pneumostasis were observed visually at the completion of the procedure. In 2 of 2 chronic animals (100%), hemostasis and pneumostasis persisted for the 7-day observation period. Histologic examination of the excised samples showed preservation of the core parenchymal architecture without evident tissue damage of the samples that would impair pathologic analysis. CONCLUSIONS: Percutaneous resection of targeted lung tissue with the MiTR system demonstrated hemostasis and pneumostasis while obtaining a histologically intact sample. After regulatory approval, the use of this device could offer more tissue for analysis than a transthoracic needle biopsy or bronchoscopy and a far less invasive alternative to video-assisted thoracic surgery or thoracotomy. This may also expand patient and physician options for the early diagnosis and treatment of lung cancer.

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Letter to the Editor Ross procedure valve function, clinical outcomes and predictors after 25 years follow up.

The following letter presents an answer of a comment of our work titled "Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up," recently published in your journal by Rangwala et al.1 As our colleagues point out, the Ross procedure has excellent survival rates but a significant risk of valve dysfunction and therefore reintervention at follow-up. Although the survival advantage with the Ross procedure appears to be consistent compared with mechanical valve substitutes, this benefit is not as clear compared with biological valve substitutes. However, biological valve substitutes also have significant reintervention rates during follow-up. The different surgical modifications of the Ross procedure have not clearly demonstrated better results in follow-up in terms of autograft reintervention. This procedure can be performed in a medium-volume center with good results as long as adequate patient selection and adequate surgical training are carried out.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

[Spanish version of the Nordic Musculoskeletal Questionnaire: cross-cultural adaptation and validation in nursing aides].

BACKGROUND: The aim of this study is to translate, culturally adapt, and validate a Spanish version of the Nordic Musculoskeletal Questionnaire for a sample of nursing assistant aides. METHODS: The questionnaire was translated and culturally adapted. Next, it was included in a battery of tests that was completed by 526 nursing assistants working in residential care homes in the Principality of Asturias (Spain). To assess its validity, the Exploratory Factor Analysis and the Confirmatory Factor Analysis were used. The internal consistency was estimated with McDonald's Omega coefficient (?), complemented by the test-retest reliability analysis through the intraclass correlation coefficient. The validity of the criteria was established by the correlation between total score on the test and quality of life measures, job insecurity and psychological demand, and social support at work. RESULTS: The Exploratory Factor Analysis and Confirmatory Factor Analysis adjustment indices confirmed it is a unidimensional test. The internal consistency values indicated very high reliability (? = 0.81). Similarly, the intraclass correlation coefficient showed statistically significant values and an excellent correlation coefficient (r = 0.95). The validity of the criteria showed a statistically significant correlation with all the constructs studied, particularly with quality of life. CONCLUSIONS: This Spanish version of the Nordic Musculoskeletal Questionnaire has good psychometric qualities for a population of nursing aides and therefore may be a valid and reliable tool for assessing musculoskeletal disorders.

Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics.

Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.

ERCP for common bile duct stones in the elderly: refine the procedure to improve outcomes.

Removal of common bile duct stones in patients with a previous cholecystectomy was one of the first indications for ERCP with biliary sphincterotomy. Thanks to a minimally invasive procedure, patients were prevented from having a new operation. Subsequently, as the technique proved to be successful, ERCP was extended to all patients with choledocholithiasis, regardless of whether or not they had gallbladder. Also contributing was the fact that, at least in the beginnings, surgical interventions on the bile duct with laparoscopic cholecystectomy were more difficult. Nowadays, many surgeons prefer to perform cholecystectomy with a bile duct clean of stones. In this issue of the Spanish Journal of Gastroenterology, Gardenyes et al. present a study on ERCP for common bile duct stones in elderly patients. The novelty of this study is not only to analyze the ERCP procedure, which we already knew has similar success and complication rates to younger patients, but also to focus on the long-term outcome, considering the frailty that frequently accompanies aging. The study concludes that older patients may benefit from enhanced care protocols to reduce medical adverse events and improve outcomes. For us gastroenterologists and endoscopists, another conclusion that can be drawn from this study is that we should not be satisfied that ERCP in older patients has the same success and complication rates as in younger patients, but rather we should strive to ensure that the results are even better.