Exploring risk factors of severe pituitary apoplexy: Insights from a multicenter study of 71 cases.

PURPOSE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). CONCLUSION: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.

Epigenetic differences between wild and cultivated grapevines highlight the contribution of DNA methylation during crop domestication.

The domestication process in grapevines has facilitated the fixation of desired traits. Nowadays, vegetative propagation through cuttings enables easier preservation of these genotypes compared to sexual reproduction. Nonetheless, even with vegetative propagation, various phenotypes are often present within the same vineyard due to the accumulation of somatic mutations. These mutations are not the sole factors influencing phenotype. Alongside somatic variations, epigenetic variation has been proposed as a pivotal player in regulating phenotypic variability acquired during domestication. The emergence of these epialleles might have significantly influenced grapevine domestication over time. This study aims to investigate the impact of domestication on methylation patterns in cultivated grapevines. Reduced-representation bisulfite sequencing was conducted on 18 cultivated and wild accessions. Results revealed that cultivated grapevines exhibited higher methylation levels than their wild counterparts. Differential Methylation Analysis between wild and cultivated grapevines identified a total of 9955 differentially methylated cytosines, of which 78% were hypermethylated in cultivated grapevines. Functional analysis shows that core methylated genes (consistently methylated in both wild and cultivated accessions) are associated with stress response and terpenoid/isoprenoid metabolic processes. Meanwhile, genes with differential methylation are linked to protein targeting to the peroxisome, ethylene regulation, histone modifications, and defense response. Collectively, our results highlight the significant roles that epialleles may have played throughout the domestication history of grapevines.

Source apportionment of ambient pollution levels in Guayaquil, Ecuador.

In this study, the relative contributions of main emission sources to the typical ambient concentrations of key pollutants, such as sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matter (PM10 and PM2.5) in Guayaquil, Ecuador, were investigated. A previous urban emissions inventory for mobile sources was expanded to include other transportation means and main industrial activities using the EMEP/EEA methodology to achieve this objective. The WRF/CALMET/CALPUFF modeling system was used to simulate the annual spatiotemporal distribution of air pollution in the city. According to the model, NO2 concentrations exceed the yearly value and 1-h Ecuadorian standards (40 and 200 µg/m3) in 1 % and 6 % of the cells of the modeling domain, respectively. These hotspots related to local sources were located in the northwest center of the city. The contributions of the manufacturing sector, thermal power plants, ports, airports, and road traffic were assessed individually, and the results indicated that air quality in the study area was strongly dominated by road traffic. The contributions of NO2, CO, PM10, and PM2.5 at the city level reached 76 %, 96 %, 90 %, and 92 % of the annual mean, respectively. In the case of SO2, the manufacturing sector made the most significant contribution (75 %), followed by thermal power plants (16 %). Furthermore, an analysis at 14 specific locations across Guayaquil identified spatial variations that may support the design and development of an air quality monitoring network for the city.

Signal execution modes emerge in biochemical reaction networks calibrated to experimental data.

Mathematical models of biomolecular networks are commonly used to study cellular processes; however, their usefulness to explain and predict dynamic behaviors is often questioned due to the unclear relationship between parameter uncertainty and network dynamics. In this work, we introduce PyDyNo (Python dynamic analysis of biochemical networks), a non-equilibrium reaction-flux based analysis to identify dominant reaction paths within a biochemical reaction network calibrated to experimental data. We first show, in a simplified apoptosis execution model, that despite the thousands of parameter vectors with equally good fits to experimental data, our framework identifies the dynamic differences between these parameter sets and outputs three dominant execution modes, which exhibit varying sensitivity to perturbations. We then apply our methodology to JAK2/STAT5 network in colony-forming unit-erythroid (CFU-E) cells and provide previously unrecognized mechanistic explanation for the survival responses of CFU-E cell population that would have been impossible to deduce with traditional protein-concentration based analyses.

Colonic Metastasis in a Patient With Hereditary Diffuse Gastric Cancer: A Case Report.

Metastasis of gastric carcinoma to atypical locations can complicate management, often leading clinicians to rely heavily on chemotherapy. While instances of gastric carcinoma spreading to the liver, peritoneum, and lymphatics are well documented in the literature, there is limited evidence of its spread to intraintestinal organs, particularly the colon. This scarcity of reports complicates diagnosis, given the variations in histopathology. This case report highlights a 35-year-old patient diagnosed with colonic metastasis from hereditary diffuse gastric cancer (HDGC) while being evaluated for potential causes of iron deficiency anemia. A mutation in the E-cadherin (CDH1) tumor suppressor gene is associated with HDGC. Dysregulation of CDH1 leads to tumor proliferation, invasion, migration, and metastasis. Treatment options for gastric cancer include surgical resection with neoadjuvant or adjuvant chemotherapy or palliative care with chemotherapy in metastatic disease. Although colonic metastasis from gastric cancer is rare, documented incidents can offer valuable insights that avoid misdiagnosing primary tumors and help guide further management.

Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.

Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital.

BACKGROUND: Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. METHODS: A single-center retrospective cohort study of 100 consecutive patients hospitalized for "Killip IV AMI" between 2016 and 2023 was performed to reclassify patients according to SCAI stage. RESULTS: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19-1.06; P=0.058). CONCLUSIONS: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.

A review concerning the breast cancer-related tumour microenvironment.

Breast cancer (BC) is currently the most common malignant tumour in women and one of the leading causes of their death around the world. New and increasingly personalised diagnostic and therapeutic tools have been introduced over the last few decades, along with significant advances regarding the study and knowledge related to BC. The tumour microenvironment (TME) refers to the tumour cell-associated cellular and molecular environment which can influence conditions affecting tumour development and progression. The TME is composed of immune cells, stromal cells, extracellular matrix (ECM) and signalling molecules secreted by these different cell types. Ever deeper understanding of TME composition changes during tumour development and progression will enable new and more innovative therapeutic strategies to become developed for targeting tumours during specific stages of its evolution. This review summarises the role of BC-related TME components and their influence on tumour progression and the development of resistance to therapy. In addition, an account on the modifications in BC-related TME components associated with therapy is given, and the completed or ongoing clinical trials related to this topic are presented.

A Novel Missense Variant in the NKX2-1 Homeodomain Prevents Transcriptional Rescue by TAZ.

Background: Brain-lung-thyroid syndrome (BLTS) is caused by NKX2-1 haploinsufficiency, resulting in chorea/choreoathetosis, respiratory problems, and hypothyroidism. Genes interacting with NKX2-1 mutants influence its phenotypic variability. We report a novel NKX2-1 missense variant and the modifier function of TAZ/WWTR1 in BLTS. Methods: A child with BLTS underwent next-generation sequencing panel testing for thyroid disorders. His family was genotyped for NKX2-1 variants and screened for germline mosaicism. Mutant NKX2-1 was generated, and transactivation assays were performed on three NKX2-1 target gene promoters. DNA binding capacity and protein-protein interaction were analyzed. Results: The patient had severe BLTS and carried a novel missense variant c.632A>G (p.N211S) in NKX2-1, which failed to bind to specific DNA promoters, reducing their transactivation. TAZ cotransfection did not significantly increase transcription of these genes, although the variant retained its ability to bind to TAZ. Conclusions: We identify a novel pathogenic NKX2-1 variant that causes severe BLTS and is inherited through germline mosaicism. The mutant lacks DNA-binding capacity, impairing transactivation and suggesting that NKX2-1 binding to DNA is essential for TAZ-mediated transcriptional rescue.

The Great Mimicker Gets Caught: A Rare Case of Syphilis in the Gastrointestinal Tract.

Syphilis is a sexually transmitted disease that impacts multiple organ systems and can mimic various diseases and is an extremely rare cause of proctitis in men who have sex with men and transgender females. We present a case of a 49-year-old transgender female with a medical history significant for diabetes mellitus and hyperlipidemia who presented to the emergency department with dull abdominal pain in the left upper and lower quadrants for two days. She had non-bloody, nonbilious emesis, 10-pound weight loss over 1 month, and constipation for 2 weeks. Laboratory results showed a cholestatic pattern. Computed tomography of the abdomen showed rectal wall thickening, multiple enlarged perirectal adenopathy, and mild inflammatory infiltration around the rectum suggesting superimposed proctitis. On colonoscopy, a possible rectal mass or severe proctitis with near complete obstruction was seen with initial pathology concerning for lymphoma or a rare type of colitis. The patient was empirically started on ceftriaxone and doxycycline leading to improvement in inflammation. Special stains requested were positive for Treponema pallidum confirming the diagnosis of syphilitic proctitis and highly suggestive syphilitic hepatitis. Few cases of syphilitic proctitis imitating rectal malignancy and syphilitic hepatitis have been reported. Syphilis requires exclusion as well as confirmation of spirochetes for high-risk populations with special staining. It is important to diagnose syphilis in special populations that are at high risk of contraction.

Gender disparities in lost productivity resulting from non-communicable diseases in Mexico, 2005-2021.

Background: Non-communicable diseases (NCDs) cause long-term impacts on health and can substantially affect people's ability to work. Little is known about how such impacts vary by gender, particularly in low- and middle-income countries (LMICs), where productivity losses may affect economic development. This study assessed the long-term productivity loss caused by major NCDs among adult women and men (20-76 years) in Mexico because of premature death and hospitalisations, between 2005 and 2021. Methods: We conducted an economic valuation based on the Human Capital Approach. We obtained population-based data from the National Employment Survey from 2005 to 2021 to estimate the expected productivity according to age and gender using a two-part model. We utilised expected productivity based on wage rates to calculate the productivity loss, employing Mexican official mortality registries and hospital discharge microdata for the same period. To assess the variability in our estimations, we performed sensitivity analyses under two different scenarios. Results: Premature mortality by cancers, diabetes, chronic cardiovascular diseases (CVD), chronic respiratory diseases (CRD) and chronic kidney disease (CKD) caused a productivity loss of 102.6 billion international US dollars (Intl. USD) from 2.8 million premature deaths. Seventy-three percent of this productivity loss was observed among men. Cancers caused 38.3% of the productivity loss (mainly among women), diabetes 38.1, CVD 15.1, CRD 3.2, and CKD 5.3%. Regarding hospitalisations, the estimated productivity loss was 729.7 million Intl. USD from 54.2 million days of hospitalisation. Men faced 65.4 and women 34.6% of these costs. Cancers caused 41.3% of the productivity loss mainly by women, followed by diabetes (22.1%), CKD (20.4%), CVD (13.6%) and CRD (2.6%). Conclusions: Major NCDs impose substantial costs from lost productivity in Mexico and these tend to be higher amongst men, while for some diseases the economic burden is higher for women. This should be considered to inform policymakers to design effective gender-sensitive health and social protection interventions to tackle the burden of NCDs.

Parenchymal obliteration by renal masses: Functional and oncologic implications.

OBJECTIVES: Most renal tumors merely displace nephrons while others can obliterate parenchyma in an invasive manner. Substantial parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) may have oncologic implications; however, studies regarding PVR remain limited. Our objective was to evaluate the oncologic implications associated with PVR using improved methodology including more accurate and objective tools. PATIENTS/METHODS: A total of 1,222 patients with non-metastatic renal tumors managed with partial nephrectomy (PN) or radical nephrectomy (RN) at Cleveland Clinic (2011-2014) with necessary studies were retrospectively evaluated. Parenchymal volume analysis via semiautomated software was used to estimate split renal function and preoperative parenchymal volumes. Using the contralateral kidney as a control, %PVR was defined: (parenchymal volumecontralateral-parenchymal volumeipsilateral) normalized by parenchymal volumecontralateral x100%. PVR was determined preoperatively and not altered by management. Patients were grouped by degree of PVR: minimal (<5%, N = 566), modest (5%-25%, N = 414), and prominent (≥25%, N = 142). Kaplan-Meier was used to evaluate survival outcomes relative to degree of PVR. Multivariable Cox-regression models evaluated predictors of recurrence-free survival (RFS). RESULTS: Of 1,122 patients, 801 (71%) were selected for PN and 321 (29%) for RN. Overall, median tumor size was 3.1 cm and 6.8 cm for PN and RN, respectively, and median follow-up was 8.6 years. Median %PVR was 15% (IQR = 6%-29%) for patients selected for RN and negligible for those selected for PN. %PVR correlated inversely with preoperative ipsilateral GFR (r = -0.49, P < 0.01) and directly with advanced pathologic stage, high tumor grade, clear cell histology, and sarcomatoid features (all P < 0.01). PVR≥25% associated with shortened recurrence-free, cancer-specific, and overall survival (all P < 0.01). Male sex, ≥pT3a, tumor grade 4, positive surgical margins, and PVR≥25% independently associated with reduced RFS (all P < 0.02). CONCLUSIONS: Obliteration of normal parenchyma by RCC substantially impacts preoperative renal function and patient selection. Our data suggests that increased PVR is primarily driven by aggressive tumor characteristics and independently associates with reduced RFS, although further studies will be needed to substantiate our findings.

Unveiling the Genetic Blueprint of a Desert Scorpion: A Chromosome-level Genome of Hadrurus arizonensis Provides the First Reference for Parvorder Iurida.

Over 400 million years old, scorpions represent an ancient group of arachnids and one of the first animals to adapt to life on land. Presently, the lack of available genomes within scorpions hinders research on their evolution. This study leverages ultralong nanopore sequencing and Pore-C to generate the first chromosome-level assembly and annotation for the desert hairy scorpion, Hadrurus arizonensis. The assembled genome is 2.23 Gb in size with an N50 of 280 Mb. Pore-C scaffolding reoriented 99.6% of bases into nine chromosomes and BUSCO identified 998 (98.6%) complete arthropod single copy orthologs. Repetitive elements represent 54.69% of the assembled bases, including 872,874 (29.39%) LINE elements. A total of 18,996 protein-coding genes and 75,256 transcripts were predicted, and extracted protein sequences yielded a BUSCO score of 97.2%. This is the first genome assembled and annotated within the family Hadruridae, representing a crucial resource for closing gaps in genomic knowledge of scorpions, resolving arachnid phylogeny, and advancing studies in comparative and functional genomics.

Multi-organ clinical ultrasound as a complement to the diagnostic process in an internal medicine consultation.

INTRODUCTION: Evaluating outpatient cases in internal medicine consultations presents a significant diagnostic challenge. Ultrasound can be a highly useful tool in assessment and decision-making. PATIENTS AND METHODS: A prospective observational study was conducted on a cohort of patients attending an internal medicine rapid assessment clinic. Eighty patients were prospectively recruited. A medical consultation was conducted as per usual clinical practice, followed by a POCUS evaluation; collecting pulmonary, cardiac, and abdominal data. All findings were analyzed and recorded, particularly those that were significant or altered the initial diagnosis, subsequent tests, or treatment. RESULTS: Significant ultrasound findings were found in 37.5% of the patients. Of all ultrasound scans, the most clinically relevant were in the heart region (31.9%), followed by the abdomen (26%). These findings led to a change in overall management in 27.5% of patients. Using logistic regression, a model was developed to estimate the presence of clinically relevant findings with an area under the curve (AUC) of 0.78 (95% CI 0.66-0.89; p < 0.001) with 80% Sensitivity and 66% Specificity. CONCLUSION: The systematic and standardized incorporation of clinical ultrasound in internal medicine consultations contributes to decision-making, can provide significant findings that allow for modifications in clinical suspicion and therapeutic management.

Acute physiological and psychological responses during an incremental treadmill test wearing a new upper-body sports garment with elastomeric technology.

Background: The use of elastomeric technology in sports garments is increasing in popularity; however, its specific impact on physiological and psychological variables is not fully understood. Thus, we aimed to analyze the physiological (muscle activation of the pectoralis major, triceps brachii, anterior deltoid, and rectus abdominis, capillary blood lactate, systolic and diastolic blood pressure, and heart rate) and psychological (global and respiratory rating of perceived exertion [RPE]) responses during an incremental treadmill test wearing a new sports garment for the upper body that incorporates elastomeric technology or a placebo garment. Methods: Eighteen physically active young adults participated in two randomized sessions, one wearing the elastomeric garment and the other wearing a placebo. Participants performed in both sessions the same treadmill incremental test (i.e., starting at 8 km/h, an increase of 2 km/h each stage, stage duration of 3 min, and inclination of 1%; the test ended after completing the 18 km/h Stage or participant volitional exhaustion). The dependent variables were assessed before, during, and/or after the test. Nonparametric tests evaluated differences. Results: The elastomeric garment led to a greater muscle activation (p < 0.05) in the pectoralis major at 16 km/h (+33.35%, p = 0.01, d = 0.47) and 18 km/h (+32.09%, p = 0.02, d = 0.55) and in the triceps brachii at 10 km/h (+20.28%, p = 0.01, d = 0.41) and 12 km/h (+34.95%, p = 0.04, d = 0.28). Additionally, lower lactate was observed at the end of the test (-7.81%, p = 0.01, d = 0.68) and after 5 min of recovery (-13.71%, p < 0.001, d = 1.00) with the elastomeric garment. Nonsignificant differences between the garments were encountered in the time to exhaustion, cardiovascular responses, or ratings of perceived exertion. Conclusion: These findings suggest that elastomeric garments enhance physiological responses (muscle activation and blood lactate) during an incremental treadmill test without impairing physical performance or effort perception.

Polysomnographic parameters associated with cognitive function in patients with major depression and insomnia.

OBJECTIVE: To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF. METHOD: Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF. RESULTS: Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF. CONCLUSION: Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.