T1 mapping in the rat myocardium at 7 Tesla using a modified CINE inversion recovery sequence

Purpose To evaluate the reproducibility and sensitivity of the modified CINE inversion recovery (mCINE-IR) acquisition on rats for measuring the myocardial T1 at 7 Tesla. Materials and Methods The recently published mCINE-IR acquisition on humans was applied on rats for the first time, enabling the possibility of translational studies with an identical sequence. Simulations were used to study signal evolution and heart rate dependency. Gadolinium phantoms, a heart specimen and a healthy rat were used to study reproducibility. Two cryo-infarcted rats were scanned to measure late gadolinium enhancement (LGE). Results In the phantom reproducibility studies the T1 measurements had a maximum coefficient of variation (COV) of 1.3%. For the in vivo reproducibility the COV was below 5% in the anterior cardiac segments. In simulations with phantoms and specimens, a heart rate dependency of approximately 0.5 ms/bpm was present. The T1 maps of the cryo-infarcted rats showed a clear lowering of T1 in de LGE region. Conclusion The results show that mCINE-IR is highly reproducible and that the sensitivity allows detecting T1 changes in the rat myocardium

Trends in modeling Biomedical Complex Systems

In this paper we provide an introduction to the techniques for multi-scale complex biological systems, from the single bio-molecule to the cell, combining theoretical modeling, experiments, informatics tools and technologies suitable for biological and biomedical research, which are becoming increasingly multidisciplinary, multidimensional and information-driven. The most important concepts on mathematical modeling methodologies and statistical inference, bioinformatics and standards tools to investigate complex biomedical systems are discussed and the prominent literature useful to both the practitioner and the theoretician are presented

Stochastic neutral modelling of the Gut Microbiota’s relative species abundance from next generation sequencing data

BACKGROUND: Interest in understanding the mechanisms that lead to a particular composition of the Gut Microbiota is highly increasing, due to the relationship between this ecosystem and the host health state. Particularly relevant is the study of the Relative Species Abundance (RSA) distribution, that is a component of biodiversity and measures the number of species having a given number of individuals. It is the universal behaviour of RSA that induced many ecologists to look for theoretical explanations. In particular, a simple stochastic neutral model was proposed by Volkov et al. relying on population dynamics and was proved to fit the coral-reefs and rain forests RSA. Our aim is to ascertain if this model also describes the Microbiota RSA and if it can help in explaining the Microbiota plasticity. RESULTS: We analyzed 16S rRNA sequencing data sampled from the Microbiota of three different animal species by Jeraldo et al. Through a clustering procedure (UCLUST), we built the Operational Taxonomic Units. These correspond to bacterial species considered at a given phylogenetic level defined by the similarity threshold used in the clustering procedure. The RSAs, plotted in the form of Preston plot, were fitted with Volkov’s model. The model fits well the Microbiota RSA, except in the tail region, that shows a deviation from the neutrality assumption. Looking at the model parameters we were able to discriminate between different animal species, giving also a biological explanation. Moreover, the biodiversity estimator obtained by Volkov’s model also differentiates the animal species and is in good agreement with the first and second order Hill’s numbers, that are common evenness indexes simply based on the fraction of individuals per species. CONCLUSIONS: We conclude that the neutrality assumption is a good approximation for the Microbiota dynamics and the observation that Volkov’s model works for this ecosystem is a further proof of the RSA universality. Moreover, the ability to separate different animals with the model parameters and biodiversity number are promising results if we think about future applications on human data, in which the Microbiota composition and biodiversity are in close relationships with a variety of diseases and life-styles

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Identification of human cytomegalovirus isolates by the polymerase chain reaction

Fifty human cytomegalovirus (HCMV) isolates were recovered from different clinical specimens (buffy coat, throat washing and urine) obtained from fifty patients (23 AIDS patients, 20 heart transplant recipients, 1 bone marrow transplant recipient, 2 newborns with congenital HCMV infection and 4 immunocompetent individuals with acute HCMV infection). The isolates were previously identified by immunological methods and then examined for identification by the polymerase chain reaction. In parallel, reference HCMV strains as well as other human members of the Herpesviridae family (reference and wild strains) were examined as controls. Two pairs of primers relevant to the immediate-early and late regions of HCMV DNA, respectively, were used. The DNA amplification product was highly specific; in addition, all fifty HCMV isolates were amplified by both pairs of primers and thus identified as HCMV. These preliminary results show that selected pairs of primers are able to amplify DNA regions conserved enough to allow virus identification among a large number of HCMV strains. In addition, they are highly promising in view of the use of PCR for direct detection of HCMV DNA in clinical samples

Towards a systems biology approach to mammalian cell cycle: Modeling the entrance into S phase of quiescent fibroblasts after serum stimulation

Background: The cell cycle is a complex process that allows eukaryotic cells to replicate chromosomal DNA and partition it into two daughter cells. A relevant regulatory step is in the G0/G1phase, a point called the restriction (R) point where intracellular and extracellular signals are monitored and integrated. Results: Subcellular localization of cell cycle proteins is increasingly recognized as a major factor that regulates cell cycle transitions. Nevertheless, current mathematical models of the G1/S networks of mammalian cells do not consider this aspect. Hence, there is a need for a computational model that incorporates this regulatory aspect that has a relevant role in cancer, since altered localization of key cell cycle players, notably of inhibitors of cyclin-dependent kinases, has been reported to occur in neoplastic cells and to be linked to cancer aggressiveness. Conclusion: The network of the model components involved in the G1to S transition process was identified through a literature and web-based data mining and the corresponding wiring diagram of the G1to S transition drawn with Cell Designer notation. The model has been implemented in Mathematica using Ordinary Differential Equations. Time-courses of level and of sub-cellular localization of key cell cycle players in mouse fibroblasts re-entering the cell cycle after serum starvation/re-feeding have been used to constrain network design and parameter determination. The model allows to recapitulate events from growth factor stimulation to the onset of S phase. The R point estimated by simulation is consistent with the R point experimentally determined. The major element of novelty of our model of the G1to S transition is the explicit modeling of cytoplasmic/nuclear shuttling of cyclins, cyclin-dependent kinases, their inhibitor and complexes. Sensitivity analysis of the network performance newly reveals that the biological effect brought about by Cki overexpression is strictly dependent on whether the Cki is promoting nuclear translocation of cyclin/Cdk containing complexes. © 2009 Alfieri et al; licensee BioMed Central Ltd

Identification of human cytomegalovirus isolates by the polymerase chain reaction

Fifty human cytomegalovirus (HCMV) isolates were recovered from different clinical specimens (buffy coat, throat washing and urine) obtained from fifty patients (23 AIDS patients, 20 heart transplant recipients, 1 bone marrow transplant recipient, 2 newborns with congenital HCMV infection and 4 immunocompetent individuals with acute HCMV infection). The isolates were previously identified by immunological methods and then examined for identification by the polymerase chain reaction. In parallel, reference HCMV strains as well as other human members of the Herpesviridae family (reference and wild strains) were examined as controls. Two pairs of primers relevant to the immediate-early and late regions of HCMV DNA, respectively, were used. The DNA amplification product was highly specific; in addition, all fifty HCMV isolates were amplified by both pairs of primers and thus identified as HCMV. These preliminary results show that selected pairs of primers are able to amplify DNA regions conserved enough to allow virus identification among a large number of HCMV strains. In addition, they are highly promising in view of the use of PCR for direct detection of HCMV DNA in clinical samples