Isotope and morphometrical evidence reveals the technological package associated with agriculture adoption in western Europe.

This study aimed to reconstruct the environmental conditions and the crop management practices and plant characteristics when agriculture appeared in western Europe. We analyzed oak charcoal and a large number of cereal caryopsides recovered from La Draga (Girona, Spain), an early (5300 to 4800 cal. BC) agricultural site from the Iberian Peninsula. The carbon isotope discrimination (Δ13C) values of oak, the dominant forest species in the region, indicates prevalence of a wet climate at the site. Further, we reconstructed crop management conditions, achievable yield, and crop characteristics through the analysis of Δ13C, nitrogen isotope composition (δ15N), nitrogen content, and the reconstructed weight of wheat and barley caryopsides, following protocols developed by our team [Araus et al., Nat. Commun. 5, 3953 (2014)] and comparison of these parameters with present-day organic agriculture in the region. In parallel, a regional perspective was achieved through the study of wheat and barley grains of seventeen Neolithic sites from the western Mediterranean. The results suggest that rather than small-garden cultivation, a more extensive agriculture was practiced under good water availability and moderate manuring. Moreover, results from La Draga evidence that grain weight and spike morphology were comparable to contemporary cereals. Growing conditions and the prevalence of improved crop traits indicate that agriculture was fairly consolidated at the time it reached the western edge of Europe.

Protective effects of Ruscus extract in combination with ascorbic acid and hesperidine methylchalcone on increased leukocyte-endothelial interaction and macromolecular permeability induced by ischemia reperfusion injury.

BACKGROUND: Despite the well-recognized effectiveness of Ruscus aculetus extract combined or not with ascorbic acid (AA) and hesperidine methyl chalcone (HMC) on ischemia reperfusion (I/R) injury protection, little is known about the contribution of each constituent for this effect. OBJECTIVE: To investigate the effects of AA and HMC combined or not with Ruscus extract on increased macromolecular permeability and leukocyte-endothelium interaction induced by I/R injury. METHODS: Hamsters were treated daily during two weeks with filtered water (placebo), AA (33, 100 and 300 mg/kg/day) and HMC (50, 150 and 450 mg/kg/day) combined or not with Ruscus extract (50, 150 and 450 mg/kg/day). On the day of experiment, the cheek pouch microcirculation underwent 30 min of ischemia, and the number of rolling and adherent leukocytes and leaky sites were evaluated before ischemia and during 45 min of reperfusion. RESULTS: Ruscus extract combined with AA and HMC (Ruscus extract mixture) significantly prevented post-ischemic increase in leukocyte rolling and adhesion and macromolecular permeability compared to placebo and these effects were more prominent than AA and HMC alone on leukocyte adhesion and macromolecular leakage. CONCLUSION: Ruscus extract mixture were more effective than its isolated constituents in protect the hamster cheek pouch microcirculation against I/R injury.

Acute abdomen revealing abdominal tuberculosis complicated by a proximal jejunal perforation: Case report.

Abdominal tuberculosis (TB) remains a significant health concern globally, particularly in regions with high endemicity such as North Africa and Morocco. Despite advances in diagnostic modalities, the nonspecific presentation of abdominal TB poses challenges for timely diagnosis and management. Here, we report a case of abdominal TB in a critically state of a young man from Morocco, presenting with acute abdominal pain and signs of sepsis. Radiological investigations revealed features suggestive of intestinal perforation complicating peritoneal TB. Urgent laparotomy confirmed the diagnosis, yet the patient succumbed to advanced sepsis postoperatively. This case underscores the complexity of abdominal TB diagnosis and management, necessitating a high index of suspicion and multidisciplinary collaboration. With evolving surgical techniques and ongoing research efforts, optimizing strategies for early detection and treatment of abdominal TB remains imperative, particularly in endemic regions.

Endothelial HIFα/PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension.

Mechanisms underlying maintenance of pathological vascular hypermuscularization are poorly delineated. Herein, we investigated retention of smooth muscle cells (SMCs) coating normally unmuscularized distal pulmonary arterioles in pulmonary hypertension (PH) mediated by chronic hypoxia with or without Sugen 5416, and reversal of this pathology. With hypoxia in mice or culture, lung endothelial cells (ECs) upregulated hypoxia-inducible factor 1α (HIF1-α) and HIF2-α, which induce platelet-derived growth factor B (PDGF-B), and these factors were reduced to normoxic levels with re-normoxia. Re-normoxia reversed hypoxia-induced pulmonary vascular remodeling, but with EC HIFα overexpression during re-normoxia, pathological changes persisted. Conversely, after establishment of distal muscularization and PH, EC-specific deletion of Hif1a, Hif2a, or Pdgfb induced reversal. In human idiopathic pulmonary artery hypertension, HIF1-α, HIF2-α, PDGF-B, and autophagy-mediating gene products, including Beclin1, were upregulated in pulmonary artery SMCs and/or lung lysates. Furthermore, in mice, hypoxia-induced EC-derived PDGF-B upregulated Beclin1 in distal arteriole SMCs, and after distal muscularization was established, re-normoxia, EC Pdgfb deletion, or treatment with STI571 (which inhibits PDGF receptors) downregulated SMC Beclin1 and other autophagy products. Finally, SMC-specific Becn1 deletion induced apoptosis, reversing distal muscularization and PH mediated by hypoxia with or without Sugen 5416. Thus, chronic hypoxia induction of the HIFα/PDGF-B axis in ECs is required for non-cell-autonomous Beclin1-mediated survival of pathological distal arteriole SMCs.

Exposure to Electronic Waterpipes Increases the Risk of Occlusive Cardiovascular Disease in C57BL/6J Mice.

INTRODUCTION: It is well documented that cardiovascular disease (CVD) is the leading cause of death in the US and worldwide, with smoking being the most preventable cause. Additionally, most smokers die from thrombotic-based diseases, in which platelets play a major role. To this end, because of the proven harm of smoking, several novel tobacco products such as electronic(e)-waterpipe have been gaining popularity among different sectors of the population, partly due to their "false" safety claims. While many investigators have focused on the negative health effects of traditional cigarettes and e-cigarettes on the cardiovascular system, virtually little or nothing is known about e-waterpipes, which we investigated herein. METHODS AND MATERIALS: To investigate their occlusive CVD effects, we employed a whole-body mouse exposure model of e-waterpipe vape/smoke and exposed C57BL/6J male mice (starting at 7 weeks of age) for 1 month, with the controls exposed to clean air. Exposures took place seven times a week, according to the well-known Beirut protocol, which has been employed in many studies, as it mimics real-life waterpipe exposure scenarios; specifically, 171 puffs of 530 ml volume of the e-liquid at 2.6 s puff duration and 17 s puff interval. RESULTS: The e-waterpipe exposed mice had shortened bleeding and occlusion times, when compared to the clean air controls, indicating a prothrombotic phenotype. As for the mechanism underlying this phenotype, we found that e-waterpipe exposed platelets exhibited enhanced agonist-triggered aggregation and dense granule secretion. Also, flow cytometry analysis of surface markers of platelet activation showed that both P-selectin and integrin GPIIb-IIIa activation were enhanced in the e-waterpipe exposed platelets, relative to the controls. Finally, platelet spreading and Akt phosphorylation were also more pronounced in the exposed mice. CONCLUSION: We document that e-waterpipe exposure does exert untoward effects in the context of thrombosis-based CVD, in part, via promoting platelet hyperreactivity.

Investigation of the impact of thirdhand e-cigarette exposure on platelet function: A pre-clinical study.

INTRODUCTION: The use of e-cigarettes (ECs) has reached unprecedented levels, due to a variety of reasons, including the misconception regarding their safety. Thus, there have been efforts to characterize the effects of EC exposure, including in the context of thirdhand EC (THEC) on a host of disorders, such as cardiovascular disease (CVD). METHODS: To address this issue, we sought to characterize the effects of THEC on platelet function and thrombus formation, using a novel mouse exposure protocol that resembles real life scenarios. To assess these effects, a host of related in vivo (i.e. tail bleeding time, and ferric chloride injury induced thrombosis model) assays and in vitro platelet specific (e.g. aggregation, and dense granule secretion) investigative assays were conducted. RESULTS: Our in vivo characterization demonstrated that THEC exposed mice exhibited a prothrombotic phenotype reflected by their shortened tail bleeding (THEC: 37 ± 15 seconds, versus clean air: 183 ± 56 s) and occlusion times (THEC: 188 ± 39 s, versus clean air: 519 ± 70 s), relative to those exposed to clean air. Importantly, we found no difference in the platelet counts between the THEC and clean air mice. As for the underlying mechanism, separate experiments revealed significantly enhanced platelet aggregation, dense and alpha granule secretion, as well as integrin/GPIIb-IIIa activation and phosphatidylserine exposure in response to thrombin and ADP agonist stimulation. CONCLUSIONS: Taken together, these results provide evidence that THEC does have the capacity to increase the risk of thrombotic disease, which should increase awareness regarding its underappreciated negative health effects.

Cognitive and physiological evaluation of virtual reality training in nursing.

Virtual reality (VR) has increasingly been used in several disciplines, including nursing, a profession in high demand that is now facing a shortage. This study investigated the effectiveness and efficacy of VR hybrid training over traditional training (TR) methods. Sixteen college students were recruited and randomly assigned to get 100% TR or 50% TR and 50% VR (VR50). Participants attended a three-day program with a registered nurse, consisting of lectures and practical lab sessions. Participants' performance, training time, cognitive development, physical development, mental workload, user experience, Students' Satisfaction and Self-Confidence, and team learning were evaluated. The results showed that the VR50 performed as well as, and sometimes even better than the TR group (p-value = 0.043). VR50 group significantly had higher cognitive development and found VR easy to use and attractive (p-value < 0.05). VR-integrated training makes nurses' training more affordable and accessible while providing instant and relevant feedback.Practitioner Summary: This study assessed employment-integrated virtual training in nursing, particularly peri-care, by comparing the performance, cognitive, physical, and mental workload of traditional and integrated VR training groups. The findings of this study provide significant support for incorporating VR training into educational settings.

Sex-Dependent Occlusive Cardiovascular Disease Effects of Short-Term Thirdhand Smoke Exposure.

INTRODUCTION: Thirdhand smoke (THS) is associated with many public health and disease concerns, such as respiratory illness, cancer, lipidemia, and cardiovascular disease (CVD). We have previously shown that a moderate to long-term exposure to THS increases the risk of thrombosis. However, whether short-term exposure to THS would produce any effects remains to be discovered. Therefore, this study investigated the impact of 1-month THS exposure on platelet function, in vivo and in vitro, and on cytokine response, in a sex-dependent manner. AIMS AND METHODS: Secondhand smoke or clean air (CA) exposed upholstery materials for 1 week were kept in cages housed with 5-6 mice, and the procedure was repeated for 4 weeks. These THS-exposed mice were evaluated for thrombogenesis and platelet function assays. In addition, cytokines expression was evaluated from pooled serum. RESULTS: Compared to the CA group, THS exposure significantly shortened the tail bleeding time and carotid artery thrombus formation. Moreover, the female mice appeared more sensitive to THS exposure than males. Furthermore, platelet aggregation, dense granule secretion, and P-selectin activation markers were significantly elevated due to THS exposure. In addition, high-throughput screening showed at least 30 cytokines differentially modulated by THS in females relative to 26 in male mice. CONCLUSIONS: Collectively, these results demonstrate that 1 month of THS exposure represents a high health risk, in part, by triggering a prothrombotic phenotype that appears to be more significant in females, who are at a much higher risk for occlusive CVD. Additionally, changes in cytokine levels mediate some of the THS-induced occlusive effects. IMPLICATIONS: This study revealed that THS exposure for 1 month is detrimental to the cardiovascular health of both sexes; however, females could be more aggressively affected than males. In addition, interleukins and chemokines could be critical factors for initiating prothrombotic activity due to THS exposure.

Comprehensive characterization of IFNγ signaling in acute myeloid leukemia reveals prognostic and therapeutic strategies.

Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients. We identify monocytic AML as having a unique microenvironment characterized by IFNγ producing T and NK cells, high IFNγ signaling, and immunosuppressive features. IFNγ signaling score strongly correlates with venetoclax resistance in primary AML patient cells. Additionally, IFNγ treatment of primary AML patient cells increased venetoclax resistance. Lastly, a parsimonious 47-gene IFNγ score demonstrates robust prognostic value. In summary, our findings suggest that inhibiting IFNγ is a potential treatment strategy to overcoming venetoclax resistance and immune evasion in AML patients.

Prevalence of depression in postmyocardial infarction patients in a tertiary care center in Riyadh.

BACKGROUND: The coexistence of coronary artery disease (CAD) and depression is a growing concern, as both conditions lead to disability. Although depression is more prevalent in CAD patients than in the general population and has been associated with adverse cardiac outcomes, the underlying mechanisms linking depression and CAD are not yet fully understood. This study aims to assess the prevalence of depression in postmyocardial infarction (MI) patients as baseline data in Saudi Arabia. MATERIALS AND METHODS: A cross-sectional study was conducted at King Saud Medical City, Riyadh. The study population included male and female patients who had survived MI from January 2022 to June 2022. A sample size of 323 patients was initially planned, but only 249 patients could be included on account of exclusions. The patients underwent screening for depression using Patient Health Questionnaire-2 (PHQ-2), and those who were positive on screening were further assessed using the PHQ-9 according to DSM-5 criteria. Sociodemographic data, comorbidities, and previous cardiac interventions were collected from medical records. RESULTS: The mean age of the study participants was 57.15 years, and majority (76.6%) were males. The prevalence of previously diagnosed depression was 9.2%, and 5.2% of patients reported using antidepressant medication. According to the PHQ-9 scores, 33.33% had depression, 9% had moderate depression, and 2.4% had severe depression. There were significant associations between the severity of depression and previous CAD (P < 0.05), previous coronary artery bypass graft surgery (P < 0.05), and heart failure (P < 0.05). CONCLUSION: This study reveals a high prevalence of depression in post-MI patients at King Saud Medical City. The findings highlight the need for comprehensive management of depression in this population to improve outcomes. Further research into the underlying mechanisms linking depression and CAD to develop effective interventions is required.

Ischemic Stroke Revealing Libman-Sacks Endocarditis: A Case Report.

Libman-Sacks endocarditis (LSE) is a characteristic but rare feature of systemic lupus erythematosus (SLE), which can be found in association with antiphospholipid syndrome (APS), exposing the patient to an increased embolism risk, particularly the occurrence of ischemic stroke. We present a case involving a 64-year-old man who was admitted for ischemic stroke accompanied by a fever. Cardiac investigation revealed mitral vegetations along with severe mitral regurgitation. The diagnosis of Libman-Sacks endocarditis associated with SLE and APS was made after a laboratory work-up showing negative blood cultures and positive antibodies. This case underlines the importance of early diagnosis for better management of this pathology.

Exercise Therapy in the Management of Peripheral Arterial Disease.

The incidence and prevalence of peripheral artery disease (PAD) are increasing globally and have a marked economic burden in the United States. The American Heart Association/American College of Cardiology guidelines recommend exercise therapy as a Class 1A, but its utilization remains suboptimal. This state-of-the-art review aims to provide a comprehensive review of the most updated information available on PAD, along with its risk factors, management options, outcomes, economic burden, and the role of exercise therapy in managing PAD.

Genetic Influences on Outcomes of Psychotherapy in Borderline Personality Disorder: A Narrative Review of Implications for Personalized Treatment.

Borderline personality disorder (BPD) manifests as instability in mood, relationships, self-image, and behavior, representing a challenging mental health issue. This review scrutinizes genetic factors influencing BPD and the corresponding treatment outcomes. The primary objective of this narrative review is to illuminate the association between genetic factors and BPD treatment outcomes, discussing the potential of genetic testing for personalized therapy. The review is derived from observational and experimental studies on BPD, genetic factors, and psychotherapy from 2000 to 2023, sourced primarily through PubMed. Reviews and meta-analyses were excluded. Our review suggests that genetic factors account for 40-60% of BPD variation, with significant roles played by epigenetic alterations like DNA methylation and microRNAs, particularly in the context of childhood trauma. Gene-environment interactions are also vital for BPD's development. Treatments such as dialectical behavior therapy, mentalization-based therapy, and schema therapy have shown efficacy, with success variability possibly linked to genetic factors. However, existing research is constrained by recall bias, diverse methodologies, and limited sample sizes. Future research necessitates long-term follow-up, diverse populations, and controlled variables to enhance our comprehension of BPD treatment outcomes' genetic foundations. The review underlines the promise of personalized medicine in BPD treatment, driven by genetic insights.

Pore-forming activity of S. pneumoniae pneumolysin disrupts the paracellular localization of the epithelial adherens junction protein E-cadherin.

Streptococcus pneumoniae, a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration in vitro and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by S. pneumoniae at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of S. pneumoniae remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type S. pneumoniae restored translocation by a PLY-deficient mutant, indicating that PLY can act in trans. Investigating the contribution of S. pneumoniae infection on apical junction complexes in the absence of PMN transmigration, we found that S. pneumoniae infection triggered the cleavage and mislocalization of the adherens junction (AJ) protein E-cadherin. This disruption was PLY-dependent at MOI of 2 and was recapitulated by purified PLY, requiring its pore-forming activity. In contrast, at MOI of 20, E-cadherin disruption was independent of PLY, indicating that S. pneumoniae encodes multiple means to disrupt epithelial integrity. This disruption was insufficient to promote bacterial translocation in the absence of PMNs. Thus, S. pneumoniae triggers cleavage and mislocalization of E-cadherin through PLY-dependent and -independent mechanisms, but maximal bacterial translocation across epithelial monolayers requires PLY-dependent neutrophil transmigration.

Tall Cell Variant of Invasive Papillary Breast Carcinoma.

Tall cell variant of invasive papillary breast carcinoma is exceedingly rare, with only 30 cases reported in the literature. This report describes a case of a 47-year-old woman who presented to the clinic with bilateral breast masses on a screening mammogram. The patient was lost to follow-up, but she presented again after 4 years when the right breast mass significantly grew in size over several months. Mammography showed a 1.9 cm right breast mass and a 2.3 cm left breast mass. Ultrasound-guided core biopsy revealed right breast triple negative invasive carcinoma of the tall cell papillary variant and left breast fibroadenomatoid nodules. She underwent bilateral lumpectomies with a right sentinel lymph node biopsy and was started on chemotherapy after surgical excision.

Breast Cancer Metastasis to Colon.

Breast cancer metastasis to the colon is exceedingly rare, with only 17 reported cases in the literature thus far. This report describes a 67-year-old female who presented to the Emergency Department for large volume melena in the setting of bilateral metastatic ductal breast carcinoma, left triple negative and right HER2+, and T4N0M0 non-small cell lung cancer. On routine CT abdomen/pelvis imaging, the patient had a 7 cm mass arising from the transverse colon. Colonoscopy revealed a non-obstructing necrotic mass in the proximal descending colon. The patient underwent a partial colectomy, small bowel resection, and gastric wedge resection. The patient recovered from surgery and was discharged home with palliative services. The patient passed away four months after discharge due to numerous metastases.

Predicting thrombotic cardiovascular outcomes induced by waterpipe-associated chemicals using comparative toxicogenomic database: Genes, phenotypes, and pathways.

Hookah, or waterpipe, is a tobacco smoking device that has gained popularity in the United States. A growing body of evidence demonstrates that waterpipe smoke (WPS) is associated with various adverse effects on human health, including infectious diseases, cancer, and cardiovascular diseases (CVDs), particularly thrombotic events. However, the molecular mechanisms through which WPS contributes to disease development remain unclear. In this study, we utilized an analytical approach based on the Comparative Toxicogenomics Database (CTD) to integrate chemical, gene, phenotype, and disease data to predict potential molecular mechanisms underlying the effects of WPS, based on its chemical and toxicant profile. Our analysis revealed that CVDs were among the top disease categories with regard to the number of curated interactions with WPS chemicals. We identified 5674 genes common between those modulated by WPS chemicals and traditional tobacco smoking. The CVDs with the most curated interactions with WPS chemicals were hypertension, atherosclerosis, and myocardial infarction, whereas "particulate matter", "heavy metals", and "nicotine" showed the highest number of curated interactions with CVDs. Our analysis predicted that the potential mechanisms underlying WPS-induced thrombotic diseases involve common phenotypes, such as inflammation, apoptosis, and cell proliferation, which are shared across all thrombotic diseases and the three aforementioned chemicals. In terms of enriched signaling pathways, we identified several, including chemokine and MAPK signaling, with particulate matter exhibiting the most statistically significant association with all 12 significant signaling pathways related to WPS chemicals. Collectively, our predictive comprehensive analysis provides evidence that WPS negatively impacts health and offers insights into the potential mechanisms through which it exerts these effects. This information should guide further research to explore and better understand the WPS and other tobacco product-related health consequences.