Notes

Look at the effects associated with nicotine and also metabolites around the nicotine gum position along with the mRNA term of interleukin-1β in those that smoke together with continual periodontitis.
The objective of this study was to determine the safety, kinetics and dosimetry of 177Lu labeled prostate specific membrane antigen (PSMA) small molecules 177Lu-PSMA-I&T and 177Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methods A total of 138 patients (mean age, 70±9 y; age range 46-90 y) with progressive mCRPC and PSMA expression verified by 68Ga-PSMA-11 PET/CT underwent PRLT. 51 patients received 6.1±1.0 GBq (range, 3.4-7.6 GBq) 177Lu-PSMA I&T and 87 patients received 6.5±1.1 GBq (range, 3.5-9.0 GBq) 177Lu-PSMA-617. Dosimetry was performed in all patients on the identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results The whole-body half-lives were shorter for 177Lu PSMA I&T (35 h) as compared to 177Lu PSM and platelet counts after 177Lu-PSMA-617 and 177Lu-PSMA I&T which did not need any clinical intervention. No nephrotoxicity was observed after either 177Lu-PSMA I&T or 177Lu-PSMA-617 PRLT. Conclusion Both 177Lu-PSMA I&T and 177Lu-PSMA-617 PRLT demonstrated favorable safety in mCRPC patients. Highest absorbed dose amongst healthy organs were observed for the lacrimal and parotid glands, however, not resulting in any significant clinical sequel. 177Lu-PSMA-617 demonstrated higher whole-body and lacrimal glands absorbed dose, but lower renal doses as compared to 177Lu-PSMA-I&T. The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617. There was a large inter-patient variability of the dosimetry parameters. Therefore, individual patient-based dosimetry seems favorable for personalized PRLT.Molecular breast imaging (MBI) using 99mTc-sestamibi has advanced rapidly over the past decade. Technical advances allow lower-dose, higher-resolution imaging and biopsy capability. MBI can be used for supplemental breast cancer screening with mammography for women with dense breasts, as well as to assess neoadjuvant therapy response, evaluate disease extent, and predict breast cancer risk. This article highlights the current state of the art and future directions in MBI.
As the volume of firearms (legal and illegal) in Mexico grows, gun violence has become a major public health challenge. While studies have focused on gun-related homicides and robberies, there is a dearth of research addressing non-fatal gunshot injuries. At the same time, official government sources report limited information and undercount these injuries.

The objective of this article is threefold. First, to provide data of non-fatal gunshot injuries sustained during crimes in Mexico; second, to estimate their initial individual healthcare costs; finally, to compare those costs to those resulting from other forms of injuries. This article contributes to discussions on gun violence in Mexico and its impact on public health.

We analysed Mexico's National Crime Victimization Survey from 2014 to 2020.

We estimated that there were approximately 150 415 non-fatal gunshot injuries during crimes perpetrated from 2013 to 2019. We found that most non-fatal criminal gunshot injuries occur during a robbery and e expenses are significantly higher. Crimes involving gun-related injuries reported an average expense of 16 643 pesos and crimes involving other forms of injuries reported an average of 1281 pesos. This discrepancy highlights the health burden associated with gun violence.Decision-making on having firearms at home may be contingent on perceptions of the likelihood of their negative and positive outcomes. Using data from a nationally representative survey (n=4030) conducted during 30 July 2019 to 11 August 2019, we described how US adults living in firearm-owning households perceived the relative likelihood of firearm-related harm by injury intent ('accidentally harm self or someone else with a gun', 'injure self on purpose with a gun' and 'injure someone else on purpose with a gun') for groups at risk of compromised decision-making (children; adolescents and individuals with mental health issues, substance use disorders or cognitive impairment). We found that US adults living in firearm-owning households believe that unintentional firearm injuries are more likely than intentional self-inflicted or assault-related firearm injuries, despite evidence to the contrary. Prior evidence indicates that communicating risk in relative terms can motivate behaviour change; therefore, findings from this study might helpfully inform health communications around firearm safety.
Different stakeholders may hold varying attitudes towards artificial intelligence (AI) applications in healthcare, which may constrain their acceptance if AI developers fail to take them into account. We set out to ascertain evidence of the attitudes of clinicians, consumers, managers, researchers, regulators and industry towards AI applications in healthcare.

We undertook an exploratory analysis of articles whose titles or abstracts contained the terms 'artificial intelligence' or 'AI' and 'medical' or 'healthcare' and 'attitudes', 'perceptions', 'opinions', 'views', 'expectations'. Using a snowballing strategy, we searched PubMed and Google Scholar for articles published 1 January 2010 through 31 May 2021. We selected articles relating to non-robotic clinician-facing AI applications used to support healthcare-related tasks or decision-making.

Across 27 studies, attitudes towards AI applications in healthcare, in general, were positive, more so for those with direct experience of AI, but provided certa attitudes towards AI. Those developing and implementing applications should consider policies and processes that bridge attitudinal disconnects between different stakeholders.Mechanical stretch of cancer cells can alter their invasiveness. During mechanical ventilation, lungs may be exposed to an increased amount of stretch, but the consequences on lung tumors have not been explored. To characterize the influence of mechanical ventilation on the behavior of lung tumors, invasiveness assays and transcriptomic analyses were performed in cancer cell lines cultured in static conditions or under cyclic stretch. Mice harbouring lung melanoma implants were submitted to mechanical ventilation and metastatic spread was assessed. Additional in vivo experiments were performed to determine the mechano-dependent specificity of the response. Incidence of metastases was studied in a cohort of lung cancer patients that received mechanical ventilation compared with a matched group of non-ventilated patients. Stretch increases invasiveness in melanoma B16F10luc2 and lung adenocarcinoma A549 cells. We identified a mechanosensitive upregulation of pathways involved in cholesterol processing in vitro, leading to an increase in PCSK9 and LDLR expression, a decrease in intracellular cholesterol and preservation of cell stiffness. A course of mechanical ventilation in mice harboring melanoma implants increased brain and kidney metastases two weeks later. Blockade of PCSK9 using a monoclonal antibody increased cell cholesterol and stiffness and decreased cell invasiveness in vitro and metastasis in vivo In patients, mechanical ventilation increased PCSK9 abundance in lung tumors and the incidence of metastasis, thus decreasing survival. Our results suggest that mechanical stretch promote invasiveness of cancer cells, which may have clinically relevant consequences. Pharmacological manipulation of cholesterol endocytosis could be a novel therapeutic target in this setting.
Digital biomarkers are a promising novel method to capture clinical data in a home-setting. However, clinical validation prior to implementation is of vital importance. Dimethindene The aim of this study was to clinically validate physical activity, heart rate, sleep and FEV1 as digital biomarkers measured by a smartwatch and portable spirometer in children with asthma and cystic fibrosis (CF).

This was a prospective cohort study including 60 children with asthma and 30 children with CF (age 6-16). Participants wore a smartwatch, performed daily spirometry at home and completed a daily symptom questionnaire for 28-days. Physical activity, heart rate, sleep and FEV1 were considered candidate digital endpoints. Data from 128 healthy children was used for comparison. Reported outcomes were compliance, difference between patients and controls, correlation with disease-activity and potential to detect clinical events. Analysis was performed with linear mixed effect models.

Median compliance was 88%. On average, patients exhibited lower physical activity and FEV1 compared to healthy children, whereas the heart rate of children with asthma was higher compared to healthy children. Days with a higher symptom score were associated with lower physical activity for children with uncontrolled asthma and CF. Furthermore, FEV1 was lower and (nocturnal) heart rate was higher for both patient groups on days with more symptoms. Candidate biomarkers and showed a distinct pattern before- and after a pulmonary exacerbation.

Portable spirometer- and smartwatch-derived digital biomarkers show promise as candidate endpoints for use in clinical trials or clinical care in pediatric lung disease.
Portable spirometer- and smartwatch-derived digital biomarkers show promise as candidate endpoints for use in clinical trials or clinical care in pediatric lung disease.
Birth by cesarean section (CS) is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.

To elucidate the link between birth by CS and asthma using newborn metabolomic profiles and integrating early life gut microbiome data and cord blood immunology.

We investigated the influence of CS on liquid chromatography mass spectrometry (LC-MS) metabolomic profiles of dried blood spots from newborns of the two independent Copenhagen Prospective Studies on Asthma in Childhood cohorts,
COPSAC2010 (n=677) and COPSAC2000 (n=387). We assessed the associations between the CS metabolic profile, age one-week gut microbiome data and frequency of cord blood Tregs.

In COPSAC2010, a partial least square-discriminant analysis (PLS-DA) model showed that children born by CS
natural delivery had different metabolic profiles (AUC=0.77, p=2.2e-16), which was replicated in COPSAC2000 (AUC=0.66, p=1.2e-5). The metabolic profile of CS was significantly associated with an increased risk of asthma at school-age in both COPSAC2010 (p=0.03) and COPSAC2000 (p=0.005). CS was associated with lower abundance of tryptophan, bile acid and phenylalanine metabolites, indicative of a perturbed gut microbiota. Further, gut bacteria dominating after natural delivery,
and
were correlated with CS-discriminative microbial metabolites, suggesting maternal microbial transmission during birth regulating the newborn's metabolism. Finally, the CS metabolic profile was associated with frequency of cord blood Tregs.

These findings propose that CS is programming the risk of childhood asthma through perturbed immune responses and gut microbial colonization patterns reflected in the blood metabolome at birth.
These findings propose that CS is programming the risk of childhood asthma through perturbed immune responses and gut microbial colonization patterns reflected in the blood metabolome at birth.
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