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Irish Journal of Medical Science Aug 2023Asclepiades of Bithynia (124-40 BC) was a Greek physician who practised and taught Greek medicine in Rome. Among his many contributions, Asclepiades challenged the...
Asclepiades of Bithynia (124-40 BC) was a Greek physician who practised and taught Greek medicine in Rome. Among his many contributions, Asclepiades challenged the long-standing Hippocratic doctrine of the four humours. Influenced by Epicurean philosophy, he sought to construct a new theory of human disease, derived in part from atomic theories of chance and evolution earlier described by Democritus and Epicurus. In clinical practice, Asclepiades's approach to physical and mental illnesses was reasoned, humane, and, in many ways, ahead of its time. As a result of his many contributions and his overall approach to care, Asclepiades is now considered a pioneer of modern physical therapy, the progenitor of a more humane approach to mental illness, and, as highlighted by Yapijakis, the father of modern molecular medicine.
Topics: Male; Humans; Greece; Physicians; Medicine
PubMed: 36369601
DOI: 10.1007/s11845-022-03216-2 -
Cell Jun 2024Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell...
Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the bent-closed integrin conformation, which predominates on cell surfaces, is followed within milliseconds by two concerted changes, leg extension and headpiece opening, to give the high-affinity integrin conformation. The extended-closed integrin conformation is not an intermediate but can be directly accessed from the extended-open conformation and provides a pathway for ligand dissociation. In contrast to ligand, talin, which links the integrin β-subunit cytoplasmic domain to the actin cytoskeleton, modestly stabilizes but does not induce extension or opening. Integrin activation is thus initiated by outside-in signaling and followed by inside-out signaling. Our results further imply that talin binding is insufficient for inside-out integrin activation and that tensile force transmission through the ligand-integrin-talin-actin cytoskeleton complex is required.
Topics: Animals; Humans; Mice; Actin Cytoskeleton; Cell Adhesion; CHO Cells; Cricetulus; Integrins; Ligands; Protein Binding; Protein Conformation; Signal Transduction; Single Molecule Imaging; Talin
PubMed: 38772370
DOI: 10.1016/j.cell.2024.04.049 -
Acta Microbiologica Et Immunologica... Sep 2023Hepatitis A virus (HAV) is one of the most important etiological agents of acute viral hepatitis but comprehensive molecular epidemiological study with...
Hepatitis A virus (HAV) is one of the most important etiological agents of acute viral hepatitis but comprehensive molecular epidemiological study with chrono-phylogeographical data are not available from Hungary.Between 2003 and 2022, a total of 8,307 HAV infections were registered officially in Hungary of which 400 (4.8%) HAV IgM antibody-positive serum samples were collected countrywide. HAV genomic RNA was successfully detected in 216/400 (54%) sera by RT-PCR subsequently confirmed by sequencing. The complete nucleotide sequences of VP1 region were determined in 32 representative HAV strains. Based on the sequence analysis, 150 (69.4%) strains were characterized as HAV sub-genotype IA and 66 (30.6%) as sub-genotype IB, respectively. Based on the combined epidemiological and molecular data, epidemic, endemic, and imported HAV strains were also characterized. The first two registered countrywide outbreaks started among men-sex-with men (MSM) in 2011 (sub-genotype IA) and 2021 (sub-genotype IB), the continuously circulating endemic/domestic HAV strain (sub-genotype IA) in East Hungary and the travel-related sub-genotype IB strains from Egypt should be highlighted. All HAV strains are deposited in the HAVNET database (https://www.rivm.nl/en/havnet).In this 20-year-long comprehensive molecular epidemiological study, we report the genetic characterization and geographic distribution of endemic, epidemic and imported HAV strains for the first time in Hungary with continuous co-circulation of sub-genotypes IA and IB HAV strains since 2003. These data provide basic information about the HAV situation in the country in an international context and can promote more effective national public health intervention strategies for the prevention of HAV transmissions and infections.
Topics: Male; Humans; Hepatitis A virus; Molecular Epidemiology; Hungary; Homosexuality, Male; Travel; Phylogeny; Sexual and Gender Minorities; Travel-Related Illness; Genotype; RNA, Viral
PubMed: 37490367
DOI: 10.1556/030.2023.02099 -
Microbial Genomics Nov 2023(group B , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards...
(group B , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance M (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.
Topics: Pregnancy; Adult; Infant, Newborn; Humans; Female; Streptococcus agalactiae; Molecular Epidemiology; Phylogeny; Anti-Bacterial Agents; Databases, Factual
PubMed: 38019122
DOI: 10.1099/mgen.0.001140 -
Pathogens and Global Health Feb 2024The eradication of smallpox and the cessation of vaccination have led to the growth of the susceptible human population to poxviruses. This has led to the increasing... (Review)
Review
The eradication of smallpox and the cessation of vaccination have led to the growth of the susceptible human population to poxviruses. This has led to the increasing detection of zoonotic orthopoxviruses. Among those viruses, monkeypox virus (MPV) is the most commonly detected in Western and Central African regions. Since 2022, MPV is causing local transmission in newly affected countries all over the world. While the virus causing the current outbreak remains part of clade II (historically referred to as West African clade), it has a significant number of mutations as compared to other clade II sequences and is therefore referred to as clade IIb. It remains unclear whether those mutations may have caused a change in the virus phenotype. Vaccine effectiveness data show evidence of a high cross-protection of vaccines designed to prevent smallpox against mpox. These vaccines therefore represent a great opportunity to control human-to-human transmission, provided that their availability has short time-frames and that mistakes from the recent past (vaccine inequity) will not be reiterated.
Topics: Humans; Molecular Epidemiology; Smallpox; Mpox (monkeypox); Vaccination; Monkeypox virus; Vaccines
PubMed: 37715739
DOI: 10.1080/20477724.2023.2258641 -
Saudi Medical Journal Sep 2023Colorectal cancer (CRC) is one of the most common cancers worldwide, and one of the most common causes of cancer deaths. In recent times, significant advancements have... (Review)
Review
Colorectal cancer (CRC) is one of the most common cancers worldwide, and one of the most common causes of cancer deaths. In recent times, significant advancements have been made in elucidating the molecular alterations of the disease, and the results have been an improved understanding of CRC biology, as well as the discovery of biomarkers of diagnostic, prognostic, and therapeutic significance. In this review, an evaluation is carried out of the molecular pathology research of CRC emanating from Saudi Arabia. The verdict is that the data on the molecular alterations in CRC from Saudi patients is at best modest. This dearth of molecular pathology data is aptly reflected in the paucity of molecular markers recommended for testing by the Saudi National Cancer Centre guidelines for CRC management. Large scale multi-institutional and multiregional translational studies are required to generate molecular data that would inform diagnostic, prognostic, and risk-stratification guidelines for Saudi CRC patients.
Topics: Humans; Pathology, Molecular; Saudi Arabia; Health Facilities; Colorectal Neoplasms
PubMed: 37717975
DOI: 10.15537/smj.2023.44.9.20230257 -
Virchows Archiv : An International... Feb 2024Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal... (Review)
Review
Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal tract, oropharynx, nasopharynx, and soft tissue. Availability of new molecular techniques allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, the expanding spectrum of immunohistochemical markers facilitates a rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined classifications, while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review highlights some principal molecular alterations in head and neck neoplasms presently available to assist pathologists in the practice of diagnosis, prognostication and prediction of response to treatment.
Topics: Humans; Pathology, Molecular; Head and Neck Neoplasms; Salivary Glands; Immunohistochemistry; Pathologists
PubMed: 38217715
DOI: 10.1007/s00428-023-03731-2 -
Virchows Archiv : An International... Feb 2024The continuing evolution of treatment options in thoracic oncology requires the pathologist to regularly update diagnostic algorithms for management of tumor samples. It... (Review)
Review
The continuing evolution of treatment options in thoracic oncology requires the pathologist to regularly update diagnostic algorithms for management of tumor samples. It is essential to decide on the best way to use tissue biopsies, cytological samples, as well as liquid biopsies to identify the different mandatory predictive biomarkers of lung cancers in a short turnaround time. However, biological resources and laboratory member workforce are limited and may be not sufficient for the increased complexity of molecular pathological analyses and for complementary translational research development. In this context, the surgical pathologist is the only one who makes the decisions whether or not to send specimens to immunohistochemical and molecular pathology platforms. Moreover, the pathologist can rapidly contact the oncologist to obtain a new tissue biopsy and/or a liquid biopsy if he/she considers that the biological material is not sufficient in quantity or quality for assessment of predictive biomarkers. Inadequate control of algorithms and sampling workflow may lead to false negative, inconclusive, and incomplete findings, resulting in inappropriate choice of therapeutic strategy and potentially poor outcome for patients. International guidelines for lung cancer treatment are based on the results of the expression of different proteins and on genomic alterations. These guidelines have been established taking into consideration the best practices to be set up in clinical and molecular pathology laboratories. This review addresses the current predictive biomarkers and algorithms for use in thoracic oncology molecular pathology as well as the central role of the pathologist, notably in the molecular tumor board and her/his participation in the treatment decision-making. The perspectives in this setting will be discussed.
Topics: Female; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pathology, Molecular; Biomarkers, Tumor; Biopsy
PubMed: 37801103
DOI: 10.1007/s00428-023-03651-1 -
JAMA Network Open Nov 2023Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).
OBJECTIVE
To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.
DATA SOURCES
PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants.
STUDY SELECTION
Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported.
RESULTS
From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH.
Topics: Female; Pregnancy; Humans; Autism Spectrum Disorder; Exome Sequencing; Pathology, Molecular; Patients; Hydrocephalus
PubMed: 37991765
DOI: 10.1001/jamanetworkopen.2023.43384 -
Trends in Parasitology Feb 2024Over recent years, progress in molecular markers for genotyping malaria parasites has enabled informative studies of epidemiology and transmission dynamics. Results have... (Review)
Review
Over recent years, progress in molecular markers for genotyping malaria parasites has enabled informative studies of epidemiology and transmission dynamics. Results have highlighted the value of these tools for surveillance to support malaria control and elimination strategies. There are many different types and panels of markers available for malaria parasite genotyping, and for end users, the nuances of these markers with respect to 'use case', resolution, and accuracy, are not well defined. This review clarifies issues surrounding different molecular markers and their application to malaria control and elimination. We describe available marker panels, use cases, implications for different transmission settings, limitations, access, cost, and data accuracy. The information provided can be used as a guide for molecular epidemiology and surveillance of malaria.
Topics: Humans; Malaria; Molecular Epidemiology; Biomarkers; Malaria, Falciparum
PubMed: 38129280
DOI: 10.1016/j.pt.2023.11.006