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World Journal of Emergency Surgery :... Oct 2023The creation of an ileostomy or colostomy is a common surgical event, both in elective and in emergency context. The main aim of stoma creation is to prevent... (Review)
Review
BACKGROUND
The creation of an ileostomy or colostomy is a common surgical event, both in elective and in emergency context. The main aim of stoma creation is to prevent postoperative complications, such as the anastomotic leak. However, stoma-related complications can also occur and their morbidity is not negligible, with a rate from 20 to 70%. Most stomal complications are managed conservatively, but, when this approach is not resolutive, surgical treatment becomes necessary. The aim of this mapping review is to get a comprehensive overview on the incidence, the risk factors, and the management of the main early and late ostomy complications: stoma necrosis, mucocutaneous separation, stoma retraction, stoma prolapse, parastomal hernia, stoma stenosis, and stoma bleeding.
MATERIAL AND METHODS
A complete literature research in principal databases (PUBMED, EMBASE, SCOPUS and COCHRANE) was performed by Multidisciplinary Italian Study group for STOmas (MISSTO) for each topic, with no language restriction and limited to the years 2011-2021. An international expert panel, from MISSTO and World Society of Emergency Surgery (WSES), subsequently reviewed the different issues, endorsed the project, and approved the final manuscript.
CONCLUSION
Stoma-related complications are common and require a step-up management, from conservative stoma care to surgical stoma revision. A study of literature evidence in clinical practice for stoma creation and an improved management of stoma-related complications could significantly increase the quality of life of patients with ostomy. Solid evidence from the literature about the correct management is lacking, and an international consensus is needed to draw up new guidelines on this subject.
Topics: Humans; Quality of Life; Ostomy; Surgical Stomas; Colostomy; Ileostomy
PubMed: 37817218
DOI: 10.1186/s13017-023-00516-5 -
Nature Communications Dec 2023Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been...
Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.
Topics: Adult; Humans; Female; Pregnancy; Genome-Wide Association Study; Placenta; Telomere Shortening; Telomere; Gene Expression Profiling
PubMed: 38129441
DOI: 10.1038/s41467-023-44355-z -
Cell Discovery Mar 2024Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both...
Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both alleles simultaneously in an individual diploid cell, largely restricts the application of these methods particularly for medical applications. Here, we develop a new single-cell whole-genome sequencing method based on third-generation sequencing (TGS) platform named Refresh-seq (restriction fragment ligation-based genome amplification and TGS). It is based on restriction endonuclease cutting and ligation strategy in which two alleles in an individual cell can be cut into equal fragments and tend to be amplified simultaneously. As a new single-cell long-read genome sequencing method, Refresh-seq features much lower allele dropout rate compared with SMOOTH-seq. Furthermore, we apply Refresh-seq to 688 sperm cells and 272 female haploid cells (secondary polar bodies and parthenogenetic oocytes) from F1 hybrid mice. We acquire high-resolution genetic map of mouse meiosis recombination at low sequencing depth and reveal the sexual dimorphism in meiotic crossovers. We also phase the structure variations (deletions and insertions) in sperm cells and female haploid cells with high precision. Refresh-seq shows great performance in screening aneuploid sperm cells and oocytes due to the low allele dropout rate and has great potential for medical applications such as preimplantation genetic diagnosis.
PubMed: 38443370
DOI: 10.1038/s41421-023-00638-9 -
Scientific Reports Jun 2023In developing countries, the prevalence of intestinal parasitic infection is still significant, particularly due to geographical and socioeconomic variables. The...
In developing countries, the prevalence of intestinal parasitic infection is still significant, particularly due to geographical and socioeconomic variables. The objective of this study was to map the distribution pattern of intestinal parasitic infection in a cohort of the Egyptian population, as well as to assess associated risk factors. A cross-sectional hospital-based study was conducted on 386 patients. A single fecal specimen was collected from the study individual and examined microscopically for the detection of parasitic infection. DNA was extracted from all samples and utilized to amplify Entamoeba histolytica complex species, Cryptosporidium species, Giardia intestinalis assemblages, and Blastocystis species using PCRs. Typing of Cryptosporidium species and Giardia intestinalis assemblages was performed using restriction enzymes RasI and HaeIII respectively. While Blastocystis spp. subtypes (ST) were identified through sequencing of PCR products and phylogenetic analysis. 59.6% (230/386) of the study patients were infected with one or more intestinal parasites, 87.4%; 201/230 of patients had mono-parasitic infections, and 12.6%; 29/230 had multiple-parasitic infections (P < 0.0001). The predominant protozoa were Blastocystis, followed by Entamoeba histolytica complex, and Giardia intestinalis both as mono-parasites and as part of multiple parasites. Molecular assays showed that Blastocystis ST3, Entamoeba dispar, Giardia intestinalis assemblage B, and Cryptosporidium hominis were the most prevalent species. Intestinal parasitic infection was significantly associated with age, gender, residence, and water source. Multi-parasitism showed that residency in a rural area was a risk factor (OR 4.49; 95% CI 1.51-13.37; P = 0.007). Egyptians residing in rural areas have a high prevalence of intestinal multi-parasitism. Therefore, to lessen the prevalence and effects of these infections in this group, effective and sustainable control methods, providing health education focusing on good personal hygiene habits, and providing a safe drinking water supply should be implemented.
Topics: Humans; Cryptosporidiosis; Cross-Sectional Studies; Phylogeny; Egypt; Cryptosporidium; Intestinal Diseases, Parasitic; Giardia lamblia; Blastocystis; Entamoeba histolytica
PubMed: 37340037
DOI: 10.1038/s41598-023-36320-z -
Current Hematologic Malignancy Reports Dec 2023The length of telomeres, protective structures at the chromosome ends, is a well-established biomarker for pathological conditions including multisystemic syndromes... (Review)
Review
PURPOSE OF REVIEW
The length of telomeres, protective structures at the chromosome ends, is a well-established biomarker for pathological conditions including multisystemic syndromes called telomere biology disorders. Approaches to measure telomere length (TL) differ on whether they estimate average, distribution, or chromosome-specific TL, and each presents their own advantages and limitations.
RECENT FINDINGS
The development of long-read sequencing and publication of the telomere-to-telomere human genome reference has allowed for scalable and high-resolution TL estimation in pre-existing sequencing datasets but is still impractical as a dedicated TL test. As sequencing costs continue to fall and strategies for selectively enriching telomere regions prior to sequencing improve, these approaches may become a promising alternative to classic methods. Measurement methods rely on probe hybridization, qPCR or more recently, computational methods using sequencing data. Refinements of existing techniques and new approaches have been recently developed but a test that is accurate, simple, and scalable is still lacking.
Topics: Humans; Forecasting; Telomere
PubMed: 37947937
DOI: 10.1007/s11899-023-00717-4 -
BioRxiv : the Preprint Server For... Dec 2023Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic...
Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic features. Yet, these traditional classification approaches lack precision, especially at the level of immature blasts. Single-cell RNA-sequencing (scRNA-seq) enables precise determination of cell state using thousands of markers, thus providing an opportunity to re-examine present-day classification schemes of acute leukemia. Here, we developed a detailed reference map of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states. Cell state annotations were benchmarked against purified cell populations, and in-depth characterization of gene expression programs underlying hematopoietic differentiation was undertaken. Projection of single-cell transcriptomes from 175 samples spanning acute myeloid leukemia (AML), mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) revealed 11 subtypes involving distinct stages of hematopoietic differentiation. These included AML subtypes with notable lymphoid or erythroid lineage priming, challenging traditional diagnostic boundaries between AML, MPAL, and AEL. Quantification of lineage priming in bulk patient cohorts revealed specific genetic alterations associated with this unconventional lineage priming. Integration of transcriptional and genetic information at the single-cell level revealed how genetic subclones can induce lineage restriction, differentiation blocks, or expansion of mature myeloid cells. Furthermore, we demonstrate that distinct cellular hierarchies can co-exist within individual patients, providing insight into AML evolution in response to varying selection pressures. Together, precise mapping of hematopoietic cell states can serve as a foundation for refining disease classification in acute leukemia and understanding response or resistance to emerging therapies.
PubMed: 38234771
DOI: 10.1101/2023.12.26.573390 -
Nucleic Acids Research Jul 2023Much of the human genetics variant repertoire is composed of single nucleotide variants (SNV) and small insertion/deletions (indel) but structural variants (SV) remain a...
Much of the human genetics variant repertoire is composed of single nucleotide variants (SNV) and small insertion/deletions (indel) but structural variants (SV) remain a major part of our modified DNA. SV detection has often been a complex question to answer either because of the necessity to use different technologies (array CGH, SNP array, Karyotype, Optical Genome Mapping…) to detect each category of SV or to get an appropriate resolution (Whole Genome Sequencing). Thanks to the deluge of pangenomic analysis, Human geneticists are accumulating SV and their interpretation remains time consuming and challenging. The AnnotSV webserver (https://www.lbgi.fr/AnnotSV/) aims at being an efficient tool to (i) annotate and interpret SV potential pathogenicity in the context of human diseases, (ii) recognize potential false positive variants from all the SV identified and (iii) visualize the patient variants repertoire. The most recent developments in the AnnotSV webserver are: (i) updated annotations sources and ranking, (ii) three novel output formats to allow diverse utilization (analysis, pipelines), as well as (iii) two novel user interfaces including an interactive circos view.
Topics: Humans; Genome, Human; High-Throughput Nucleotide Sequencing; INDEL Mutation; Polymorphism, Single Nucleotide; Restriction Mapping; Sequence Analysis, DNA; Whole Genome Sequencing; Disease; Software
PubMed: 37216590
DOI: 10.1093/nar/gkad426 -
STAR Protocols Mar 2024Dinoflagellate genomes often are very large and difficult to assemble, which has until recently precluded their analysis with modern functional genomic tools. Here, we...
Dinoflagellate genomes often are very large and difficult to assemble, which has until recently precluded their analysis with modern functional genomic tools. Here, we present a protocol for mapping three-dimensional (3D) genome organization in dinoflagellates and using it for scaffolding their genome assemblies. We describe steps for crosslinking, nuclear lysis, denaturation, restriction digest, ligation, and DNA shearing and purification. We then detail procedures sequencing library generation and computational analysis, including initial Hi-C read mapping and 3D-DNA scaffolding/assembly correction. For complete details on the use and execution of this protocol, please refer to Marinov et al..
PubMed: 38483898
DOI: 10.1016/j.xpro.2024.102941 -
International Journal of Clinical... Oct 2023Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in... (Review)
Review
BACKGROUND
Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in care homes. Information provided by staff working within care homes is a factor that can influence prescribing decisions in residents with BPSD.
AIM
The review aimed to capture care home staff views towards antipsychotics for residents with BPSD and separately analyse tools utilized in the studies, mapping them onto the theory of planned behaviour (TPB).
METHOD
A comprehensive literature search published in ten databases was conducted between May and July 2020 and updated in July 2021. Studies published in full with no date restriction were included and quality assessed using CROSS checklist. A thematic framework approach was applied to extract data and study tools which were then mapped onto the TPB.
RESULTS
Fourteen studies (2059 participants) were included. Findings identified four overarching themes: attitudes toward antipsychotics (e.g. antipsychotics as an appropriate strategy and effectiveness); barriers to deprescribing (e.g. lower staff education, lack of resources and time, poor medication reviews); measures implemented (e.g. nonpharmacological interventions, medication reviews); and perceived needs of staff (e.g. need for training, financial or clinical support). Identified tools addressed seven but not all components of TPB namely, behavioural, normative and control beliefs, attitude, perceived behavioural control, intention and behaviour.
CONCLUSION
The positive attitudes toward antipsychotics, the identified barriers to deprescribing and the existing tools not addressing all components of the TPB provide the impetus for further research.
Topics: Humans; Nursing Homes; Antipsychotic Agents; Dementia; Attitude of Health Personnel
PubMed: 37773304
DOI: 10.1007/s11096-023-01645-2 -
Placenta Dec 2023In-vivo measurements of placental structure and function have the potential to improve prediction, diagnosis, and treatment planning for a wide range of pregnancy...
INTRODUCTION
In-vivo measurements of placental structure and function have the potential to improve prediction, diagnosis, and treatment planning for a wide range of pregnancy complications, such as fetal growth restriction and pre-eclampsia, and hence inform clinical decision making, ultimately improving patient outcomes. MRI is emerging as a technique with increased sensitivity to placental structure and function compared to the current clinical standard, ultrasound.
METHODS
We demonstrate and evaluate a combined diffusion-relaxation MRI acquisition and analysis pipeline on a sizable cohort of 78 normal pregnancies with gestational ages ranging from 15 + 5 to 38 + 4 weeks. Our acquisition comprises a combined T2*-diffusion MRI acquisition sequence - which is simultaneously sensitive to oxygenation, microstructure and microcirculation. We analyse our scans with a data-driven unsupervised machine learning technique, InSpect, that parsimoniously identifies distinct components in the data.
RESULTS
We identify and map seven potential placental microenvironments and reveal detailed insights into multiple microstructural and microcirculatory features of the placenta, and assess their trends across gestation.
DISCUSSION
By demonstrating direct observation of micro-scale placental structure and function, and revealing clear trends across pregnancy, our work contributes towards the development of robust imaging biomarkers for pregnancy complications and the ultimate goal of a normative model of placental development.
Topics: Pregnancy; Humans; Female; Placenta; Microcirculation; Diffusion Magnetic Resonance Imaging; Fetal Growth Retardation; Magnetic Resonance Imaging; Placentation
PubMed: 37952367
DOI: 10.1016/j.placenta.2023.11.002