Antimicrobial susceptibility of clinical Helicobacter pylori isolates and its eradication by standard triple therapy: a study in west central region of Colombia.

The aim of the present study was first to isolate Helicobacter pylori from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. H. pylori positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for H. pylori. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% P = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in Helicobacter pylori has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating H. pylori infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.

Early- and Late-Onset Alzheimer's Disease: Two Sides of the Same Coin?

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.

Time series of freshwater macroinvertebrate abundances and site characteristics of European streams and rivers.

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts.

Trefoil factor 2 expressed by the murine pancreatic acinar cells is required for the development of islets and for beta cell function during aging.

Exocrine-to-endocrine crosstalk in the pancreas is crucial to maintain beta cell function. However, the molecular mechanisms underlying this crosstalk are largely undefined. Trefoil factor 2 (Tff2) is a secreted factor known to promote the proliferation of beta cells in vitro, but its physiological role in vivo in the pancreas is unknown. Also, it remains unclear which pancreatic cell type expresses Tff2 protein. We therefore created a mouse model with a conditional knockout of Tff2 in the murine pancreas. We find that the Tff2 protein is preferentially expressed in acinar but not ductal or endocrine cells. Tff2 deficiency in the pancreas reduces beta cell mass on embryonic day 16.5. However, homozygous mutant mice are born without a reduction of beta cells and with acinar Tff3 compensation by day 7. When mice are aged to 1 year, both male and female homozygous and male heterozygous mutants develop impaired glucose tolerance without affected insulin sensitivity. Perifusion analysis reveals that the second phase of glucose-stimulated insulin secretion from islets is reduced in aged homozygous mutant compared to controls. Collectively, these results demonstrate a previously unknown role of Tff2 as an exocrine acinar cell-derived protein required for maintaining functional endocrine beta cells in mice.

In vitro characterization of Trypanosoma cruzi infection dynamics in skeletal and cardiac myotubes models suggests a potential cell-to-cell transmission in mediating cardiac pathology.

Chagas disease predominantly affects the heart, esophagus, and colon in its chronic phase. However, the precise infection mechanisms of the causal agent Trypanosoma cruzi in these tissue types remain incompletely understood. This study investigated T. cruzi infection dynamics in skeletal (SM) and cardiac myotubes (CM) differentiated from H9c2(2-1) myoblasts (control). SM and CM were generated using 1% fetal bovine serum (FBS) without or with retinoic acid, respectively. Initial invasion efficiencies and numbers of released parasites were equivalent between undifferentiated and differentiated cells (~0.3-0.6%). Concomitantly, parasite motility patterns were similar across cell lines. However, CM demonstrated significantly higher infection kinetics over time, reaching 13.26% infected cells versus 3.12% for SM and 3.70% for myoblasts at later stages. Cellular automata modeling suggested an enhanced role for cell-to-cell transmission in driving the heightened parasitism observed in CM. The increased late-stage susceptibility of CM, potentially mediated by cell-to-cell transfer mechanisms of the parasite, aligns with reported clinical tropism patterns. The myotube infection models provide novel insights into Chagas disease pathogenesis that are not fully attainable through in vivo examination alone. Expanding knowledge in this area could aid therapeutic development for this neglected illness.

Substrate Mapping for Ventricular Tachycardia Ablation Through High-Density Whole-Chamber Double Extra Stimuli: The S3 Protocol.

BACKGROUND: A partial delineation of targets for ablation of ventricular tachycardia (VT) during a stable rhythm is likely responsible for a suboptimal success rate. The abnormal low-voltage near-field functional components may be hidden within the high-amplitude far-field signal. OBJECTIVES: The aim of this study was to evaluate the benefit and feasibility of functional substrate mapping using a full-ventricle S3 protocol and to assess its colocalization with arrhythmogenic conducting channels (CCs) on late gadolinium enhancement cardiac magnetic resonance. METHODS: An S3 mapping protocol with a drive train of S1 followed by S2 (effective refractory period + 30 ms) and S3 (effective refractory period + 50 ms) from the right ventricular apex was performed in 40 consecutive patients undergoing scar-related VT ablation. Deceleration zones (DZs) and areas of late potentials (LPs) were identified for all maps. A preprocedural noninvasive substrate assessment was done using late gadolinium enhancement cardiac magnetic resonance and postprocessing with automated CC identification. RESULTS: The S3 protocol was completed in 34 of the 40 procedures (85.0%). The S3 protocol enhanced the identification of VT isthmus on the basis of DZ (89% vs 62%; P < 0.01) and LP (93% vs 78%; P = 0.04) assessment. The percentage of CCs unmasked by DZs and LPs using S3 maps was significantly higher than the ones using S2 and S1 maps (78%, 65%, and 48% [P < 0.001] and 88%, 81%, and 68% [P < 0.01], respectively). The functional substrate identified during S3 activation mapping was significantly more extensive than the one identified using S2 and S1, including a greater number of DZs (2.94, 2.47, and 1.82, respectively; P < 0.001) and a wider area of LPs (44.1, 38.2, and 29.4 cm2, respectively; P < 0.001). After VT ablation, 77.9% of patients have been VT free during a median follow-up period of 13.6 months. CONCLUSIONS: The S3 protocol was feasible in 85% of patients, allows a better identification of targets for ablation, and might improve VT ablation results.

Aortic Regurgitation: From Valvular to Myocardial Dysfunction.

Chronic aortic regurgitation (AR) leads to volume overload in the left ventricle (LV), which is well tolerated for years. In this condition, the LV usually dilates with minimal reduction in the ejection fraction (EF), even in the absence of symptoms. Echocardiography is the primary imaging test used to quantify AR. However, no single assessment of Doppler measures is accurate and precise in individual patients; therefore, the integration of multiple parameters is necessary. Recent guidelines recommend surgical treatment for severe AR in patients who are symptomatic or have an LVEF < 55% and an end-systolic diameter > 50 mm. Nevertheless, advances in imaging technology have improved the quantification of AR and the assessment of LV subclinical dysfunction. It is widely recognized that patients who undergo aortic valve replacement/repair (AVR) due to symptoms or a low LVEF experience worse outcomes than those undergoing AVR for non-Class I indications. In fact, subclinical irreversible myocardial damage may occur in clinically well-compensated and closely monitored patients while awaiting formal surgical indications. This condition could be prevented by the use of multimodal imaging parameters, in particular longitudinal LV strain and magnetic resonance imaging. In addition, better cut-off values for mortality predictors should be established. This review aims to identify simple models that integrate several echocardiographic and cardiac magnetic resonance-derived parameters to predict the optimal timing of surgical treatment in asymptomatic patients with chronic severe AR.

Exome sequencing in genuine empty follicle syndrome: Novel candidate genes.

OBJECTIVE(S): Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved in an IVF cycle despite apparently normal follicular development and meticulous follicular aspiration following ovulation induction. The EFS is called genuine (gEFS) when the trigger administration is correct. The existence of gEFS is a subject of controversy, and it is quite rare with an undetermined etiology. Genetic defects in specific genes have been demonstrated to be responsible for this condition in some patients. Our objective was to identify novel genetic variants associated with gEFS. STUDY DESIGN: We conducted a prospective observational study including 1,689 egg donors from July 2017 to February 2023. WES were performed in patients suffering gEFS. RESULTS: Only 7 patients (0.41 %) exhibited gEFS after two ovarian stimulation cycles and we subsequently performed whole exome sequencing (WES) on these patients. Following stringent filtering, we identified 6 variants in 5 affected patients as pathogenic in new candidate genes which have not been previously associated with gEFS before, but which are involved in important biological processes related to folliculogenesis. These genetic variants included c.603_618del in HMMR, c.1025_1028del in LMNB1, c.1091-1G > A in TDG, c.607C > T in HABP2, c.100 + 2 T > C in HAPLN1 and c.3592_3593del in JAG2. CONCLUSION: As a conclusion, we identified new candidate genes related to gEFS that expand the mutational spectrum of genes related to gEFS.This study show that WES might be an efficient tool to identify the genetic etiology of gEFS and provide further understanding of the pathogenic mechanism of gEFS.

Chemical sensing of common microorganisms found in biopharmaceutical industries using MIR laser spectroscopy and multivariate analysis.

Mid-infrared laser spectroscopy was used to investigate common bacteria encountered in biopharmaceutical industries. The study involved the detection of bacteria using quantum cascade laser spectroscopy coupled to a grazing angle probe (QCL-GAP). Substrates similar to surfaces commonly used in biopharmaceutical industries were used as support media for the samples. Reflectance measurements were assisted by Multivariate Analysis (MVA) to assemble a powerful spectroscopic technique with classification and identification resources. The species analyzed, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus, were used to challenge the technique's capability to discriminate from microorganisms of the same family. Principal Components Analysis and Partial Least Squares-Discriminant Analysis differentiated between the bacterial species, using QCL-GAP-MVA as the reference. Spectral differences in the bacterial membrane were used to determine if these microorganisms were present in the samples analyzed. Results herein provided effective discrimination for the bacteria under study with high sensitivity and specificity.

sEMG-Based Robust Recognition of Grasping Postures with a Machine Learning Approach for Low-Cost Hand Control.

The design and control of artificial hands remains a challenge in engineering. Popular prostheses are bio-mechanically simple with restricted manipulation capabilities, as advanced devices are pricy or abandoned due to their difficult communication with the hand. For social robots, the interpretation of human intention is key for their integration in daily life. This can be achieved with machine learning (ML) algorithms, which are barely used for grasping posture recognition. This work proposes an ML approach to recognize nine hand postures, representing 90% of the activities of daily living in real time using an sEMG human-robot interface (HRI). Data from 20 subjects wearing a Myo armband (8 sEMG signals) were gathered from the NinaPro DS5 and from experimental tests with the YCB Object Set, and they were used jointly in the development of a simple multi-layer perceptron in MATLAB, with a global percentage success of 73% using only two features. GPU-based implementations were run to select the best architecture, with generalization capabilities, robustness-versus-electrode shift, low memory expense, and real-time performance. This architecture enables the implementation of grasping posture recognition in low-cost devices, aimed at the development of affordable functional prostheses and HRI for social robots.

Emergence of epizootic hemorrhagic disease in red deer (Cervus elaphus), Spain, 2022.

Epizootic hemorrhagic disease (EHD) virus serotype 8 (EHDV-8) emerged in Spain in autumn 2022. In this study, we aimed to (1) characterize the clinical and lesional presentation of EHDV infection in European red deer (Cervus elaphus), and (2) study the spatial spread of the virus in wild ruminants in Spain after its introduction, in 2022/2023. We confirmed EHDV infection in two clinically compatible sick red deer by PCR and detection of anti-EHDV specific antibodies. EHDV infection occurred in red deer with hyperacute to acute clinical signs and lesions associated to vascular changes leading to death of the animals. Partial sequences of variable segment 2 (VP2) and segment 5 (NS1) genes of the detected viruses had >99% nucleotide identity with EHDV-8 sequences from Tunisia and Italy. In a cross-sectional serological study of EHDV in 592 wild ruminants, mainly red deer (n=578), in southwestern Spain, we detected anti-EHDV antibodies in 37 of 592 samples (6.3%; 95% confidence interval: 4.3-8.2), all from red deer and from the localities where clinical cases of EHD were confirmed in red deer. We conclude that EHDV-8 infection causes severe EHD in European red deer. The serosurvey revealed a limited spread of EHDV-8 in Spanish wild ruminant populations in the first year of virus detection in Spain.

The impact of (very) young donor age on euploid rates: An analysis of 1831 trophectoderm biopsies evaluated with 24-chromosome NGS screening in oocyte donation cycles.

RESEARCH QUESTION: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles? DESIGN: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables. RESULTS: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences. CONCLUSION: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups.

Activation of ductal progenitor-like cells from adult human pancreas requires extracellular matrix protein signaling.

Ductal progenitor-like cells are a sub-population of ductal cells in the adult human pancreas that have the potential to contribute to regenerative medicine. However, the microenvironmental cues that regulate their activation are poorly understood. Here, we establish a 3-dimensional suspension culture system containing six defined soluble factors in which primary human ductal progenitor-like and ductal non-progenitor cells survive but do not proliferate. Expansion and polarization occur when suspension cells are provided with a low concentration (5% v/v) of Matrigel, a sarcoma cell product enriched in many extracellular matrix (ECM) proteins. Screening of ECM proteins identified that collagen IV can partially recapitulate the effects of Matrigel. Inhibition of integrin α1ß1, a major collagen IV receptor, negates collagen IV- and Matrigel-stimulated effects. These results demonstrate that collagen IV is a key ECM protein that stimulates the expansion and polarization of human ductal progenitor-like and ductal non-progenitor cells via integrin α1ß1 receptor signaling.

Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis.

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.