Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug ...therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of "drug-infection interaction" to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host's response to drugs. It also highlights promising areas for future research and proposes the term "drug-infection interaction" as an extension of pharmacomicrobiomics.
In Alzheimer’s disease (AD), the age of onset (AoO) exhibits considerable variability, spanning from 40 to 90 years. Specifically, individuals diagnosed with AD and exhibiting symptoms prior to the ...age of 65 are typically classified as early onset (EOAD) cases. Notably, the apolipoprotein E (APOE) ε4 allele represents the most extensively studied genetic risk factor associated with AD. We clinically characterized and genotyped the APOEε4 allele from 101 individuals with a diagnosis of EOAD, and 69 of them were affected carriers of the autosomal dominant fully penetrant PSEN1 variant c.1292C>A (rs63750083, A431E) (PSEN1+ group), while there were 32 patients in which the genetic cause was unknown (PSEN1− group). We found a correlation between the AoO and the APOEε4 allele; patients carrying at least one APOEε4 allele showed delays, in AoO in patients in the PSEN1+ and PSEN1− groups, of 3.9 (p = 0.001) and 8.6 years (p = 0.012), respectively. The PSEN1+ group presented higher frequencies of gait disorders compared to PSEN1− group, and apraxia was more frequent with PSEN1+/APOE4+ than in the rest of the subgroup. This study shows what appears to be an inverse effect of APOEε4 in EOAD patients, as it delays AoO and modifies clinical manifestations.
KDM1A/LSD1 and ZNF217 are involved in a protein complex that participates in transcriptional regulation.
has been analysed in numerous cancers and its amplification has been associated with advanced ...stages of disease; however, a similar role for
has not been uncovered. In this study, we estimated the number of
and
gene copies in tissue samples from patients diagnosed with colorectal cancer (CRC), as well as its association with clinicopathological features in patients with CRC.
Paraffin-embedded tumour samples from 50 patients with CRC with a histopathological diagnosis of CRC were included. The number of copies of
and
genes was determined by fluorescence in situ hybridisation (FISH). We also analysed the association between copy numbers of selected genes and clinicopathological data based on multivariate analysis.
Deletion of the
gene occurred in 19 samples (38%), whereas
gene amplification was identified in 11 samples (22%). We found a significant association between lymph node metastasis or advanced tumour stage and
gene deletion (p value=0.0003 and p value=0.011, respectively).
gene deletion could be considered a novel prognostic biomarker of late-stage CRC.
Calf muscle strain and Achilles tendon injuries are common in many sports. For the treatment of muscular and tendinous injuries, one of the newer approaches in sports medicine is capacitive-resistive ...electric transfer therapy. Our objective was to analyze this in vitro, using invasive temperature measurements in cadaveric specimens.
A cross-sectional study designed with five fresh frozen cadavers (10 legs) were included in this study. Four interventions (capacitive and resistive modes; low- and high-power) was performed for 5 min each by a diathermy "T-Plus" device. Achilles tendon, musculotendinous junction and superficial temperatures were recorded at 1-min intervals and 5 min after treatment.
With the low-power capacitive protocol, at 5 min, there was a 25.21% increase in superficial temperature, a 17.50% increase in Achilles tendon temperature and an 11.27% increase in musculotendinous junction temperature, with a current flow of 0.039 A ± 0.02. With the low-power resistive protocol, there was a 1.14% increase in superficial temperature, a 28.13% increase in Achilles tendon temperature and an 11.67% increase in musculotendinous junction temperature at 5 min, with a current flow of 0.063 A ± 0.02. With the high-power capacitive protocol there was an 88.52% increase in superficial temperature, a 53.35% increase in Achilles tendon temperature and a 39.30% increase in musculotendinous junction temperature at 5 min, with a current flow of 0.095 A ± 0.03. With the high-power resistive protocol, there was a 21.34% increase in superficial temperature, a 109.70% increase in Achilles tendon temperature and an 81.49% increase in musculotendinous junction temperature at 5 min, with a current flow of 0.120 A ± 0.03.
The low-power protocols resulted in only a very slight thermal effect at the Achilles tendon and musculotendinous junction, but current flow was observed. The high-power protocols resulted in a greater temperature increase at the Achilles tendon and musculotendinous junction and a greater current flow than the low-power protocols. The high-power resistive protocol gave the greatest increase in Achilles tendon and musculotendinous junction temperature. Capacitive treatments (low- and high-power) achieved a greater increase in superficial temperature.
Background Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch ...repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. Main body Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. Conclusion Universal screening could be an option to address the problem of underdiagnosis. Keywords: Lynch Syndrome, Clinical criteria, Genetics aspects, Amsterdam, Bethesda
Colorectal cancer is a heterogeneous disease with multiple genomic changes that influence the clinical management of patients; thus, the search for new molecular targets remains necessary. The aim of ...this study was to identify genetic variants in tumor tissues from Mexican patients with colorectal cancer, using massive parallel sequencing. A total of 4813 genes were analyzed in tumoral DNA from colorectal cancer patients, using the TruSight One Sequencing panel. From these, 192 variants with clinical associations were found distributed in 168 different genes, of which 46 variants had not been previous reported in the literature or databases, although genes harboring those variants had already been described in colorectal cancer. Enrichment analysis of the affected genes was performed using Reactome software; pathway over-representation showed significance for disease, signal transduction, and immune system subsets in all patients, while exclusive subsets such as DNA repair, autophagy, and RNA metabolism were also found. Those characteristics, whether individual or shared, could give tumors specific capabilities for survival, aggressiveness, or response to treatment. Our results can be useful for future investigations targeting specific characteristics of tumors in colorectal cancer patients. The identification of exclusive or common pathways in colorectal cancer patients could be important for better diagnosis and personalized cancer treatment.
We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited ...at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical–pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical–pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26–0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.
Often bones are the only biological material left for the identification of human remains. As situations may occur where samples need to be stored for an extended period without access to cooling, ...appropriate storage of the bone samples is necessary for maintaining the integrity of DNA for profiling. To simulate DNA preservation under field conditions, pig rib bones were used to evaluate the effects of bone cleaning, buffer composition, storage temperature, and time on DNA recovery from bone samples. Bones were stored in three different buffers: TENT, solid sodium chloride, and ethanol-EDTA, at 20 °C and 35 °C for 10, 20, and 30 days. Bones were subsequently dried and ground to powder. DNA was extracted and quantified. Results show that temperature and storage time have no significant influence on DNA yield. DNA recovery from bones stored in solid sodium chloride or ethanol-EDTA was significantly higher compared to bones stored in TENT, and grinding of bones was facilitated by the extent of dehydration in solid sodium chloride and ethanol-EDTA compared to TENT. Overall, solid sodium chloride was found to be superior over ethanol-EDTA; when it comes to transportation, dry material such as salt eliminates the risk of leaking; it is non-toxic and in contrast to ethanol not classified as dangerous goods. Based on this study’s results, we recommend NaCl as a storage substrate for forensic samples in cases where no cooling/freezing conditions are available.
Early-onset Alzheimer’s disease (EOAD), defined as Alzheimer’s disease onset before 65 years of age, has been significantly less studied than the “classic” late-onset form (LOAD), although EOAD often ...presents with a more aggressive disease course, caused by variants in the APP, PSEN1, and PSEN2 genes. EOAD has significant differences from LOAD, including encompassing diverse phenotypic manifestations, increased genetic predisposition, and variations in neuropathological burden and distribution. Phenotypically, EOAD can be manifested with non-amnestic variants, sparing the hippocampi with increased tau burden. The aim of this article is to review the different genetic bases, risk factors, pathological mechanisms, and diagnostic approaches between EOAD and LOAD and to suggest steps to further our understanding. The comprehension of the monogenic form of the disease can provide valuable insights that may serve as a roadmap for understanding the common form of the disease.
Introduction and objectives
At the end of 2017, three clinical trials demonstrated that, in selected patients, percutaneous closure of patent foramen ovale (PFO) after cryptogenic stroke (CS) reduces ...the risk of recurrence. Our aim was to determine the impact of these findings on routine clinical practice in a tertiary hospital.
Methods
Patients with CS and percutaneous closure of PFO during 2001–2020 were included. The clinical characteristics of the patient and the anatomical characteristics of the foramen were analyzed. Based on both, the closure indications were classified into three groups according to the latest European recommendations and were analyzed in two periods, before and after the publication date of the clinical trials.
Results
A total of 293 patients were included. The mean age was 49 ± 11 years, and 15% were older than 60 years. The median RoPE score was 6 p25–75, 5–7 and 75% had complex anatomy (CA). After the publication of the studies, the frequency of CA and the mean age of the patients were significantly higher (89% vs. 69%
p
< 0.0005 and 51 ± 11 vs. 48 ± 11 years,
p
= 0.02, respectively), and the RoPE score, significantly lower (5 5–7 versus 6 5–7,
p
= 0.02). Inadequate closure indications were significantly reduced (8% vs. 18%,
p
= 0.02).
Conclusion
After the publication of clinical trials that have shown benefit of PFO closure after CS, the number of inappropriate indications for closure has decreased significantly in our institution, with a higher percentage of CA, despite a clinical profile suggestive of lower causal probability of PFO.
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