Partial sensory rhizotomy in recurrent trigeminal neuralgia. our experience and literature review.

BACKGROUND AND OBJECTIVE: Trigeminal Neuralgia (NT) is a common pathology in Neurosurgery. It can be classified as idiopathic or secondary to other pathologies, such as Multiple Sclerosis (MS). Several surgical treatments have been described, some of them being replaced by more modern techniques. Partial sensory rhizotomy (PSR), described by Dandy is a technique replaced by other techniques due to its permanent side effects. We present our experience with this technique in patients with recurrent NT. METHODS AND MATERIALS: A retrospective review is carried out on six patients who underwent surgery at our center from 2018 to 2023 using the PSR technique. RESULTS: All the patients intervened showed significant clinical improvement, except one patient who required reintervention due to uncontrolled pain. According to the Barrow Neurological Institute (BNI) scale, 80% (4/5) of patients showed improvement from grade V to grades I/II except for one of them. This patient suffered from MS. Additionally, one patient presented a corneal ulcer after surgery due to impairment of the corneal reflex. CONCLUSION: In our experience, PSR is a valid treatment option in selected patients with recurrent TN. It has a low incidence of complications with an adequate surgical technique and anatomical knowledge of the region. To the best of our knowledge, we are one of the few centers in Spain to publish our results with PSR in the last ten years. In our study, we report good results in pain control withdrawing medication in 67% (4/6) of the operated patients.

Interesting Cytokine Profile Caused by Clinical Strains of Pseudomonas aeruginosa MDR Carrying the exoU Gene.

Pseudomonas aeruginosa is an opportunistic pathogen in HAIs with two facets: the most studied is the high rate of antimicrobial resistance, and the less explored is the long list of virulence factors it possesses. This study aimed to characterize the virulence genes carried by strains as well as the profile of cytokines related to inflammation, according to the resistance profile presented. This study aims to identify the virulence factors associated with MDR strains, particularly those resistant to carbapenems, and assess whether there is a cytokine profile that correlates with these characteristics. As methodology species were identified by classical microbiological techniques and confirmed by molecular biology, resistance levels were determined by the minimum inhibitory concentration and identification of MDR strains. Virulence factor genotyping was performed using PCR. In addition, biofilm production was assessed using crystal violet staining. Finally, the strains were cocultured with PBMC, and cell survival and the cytokines IL-1ß, IL-6, IL-10, IL-8, and TNF-α were quantified using flow cytometry. Bacteremia and nosocomial pneumonia in adults are the most frequent types of infection. In the toxigenic aspect, genes corresponding to the type III secretion system were present in at least 50% of cases. In addition, PBMC exposed to strains of four different categories according to their resistance and toxicity showed a differential pattern of cytokine expression, a decrease in IL-10, IL-6, and IL-8, and an over-secretion of IL-1b. In conclusion, the virulence genes showed a differentiated appearance for the two most aggressive exotoxins of T3SS (exoU and exoS) in multidrug-resistant strains. Moreover, the cytokine profile displays a low expression of cytokines with anti-inflammatory and proinflammatory effects in strains carrying the exoU gene.

Drug repositioning identifies histone deacetylase inhibitors that promote innate immunity in non-tuberculous mycobacterial infection.

Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.

Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting.

Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy. This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants. No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.

Could titanium screws be an appropriate disc stabilization technique in temporomandibular joint arthroscopy?

Multiple techniques for disc fixation through temporomandibular joint arthroscopy have been described. They can be classified as non-rigid, semi-rigid, and rigid. They all offer different advantages and disadvantages, and some have greater difficulties than others. Currently, multiple modifications to the basic techniques have been described in order to facilitate the technique since disc fixation corresponds to one of the procedures that most require skill. However, each technique requires extensive evaluation and monitoring in order to avoid complications and find the benefits of each technique. For this reason, the objective of this letter to the editor is to discuss two situations observed in the previously described fixation technique with osteosynthesis screws. The first issue is the fixation mechanism, and the second is the fixation time. This is in order to continue searching for the truth among all to achieve the best results and the benefit of patients.

Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling.

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a 'normal' AVF (nAVF) group and an 'outliers' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.

Can upwelling regions be potential thermal refugia for marine fishes during climate warming?

Species are expected to migrate to higher latitudes as warming intensifies due to anthropogenic climate change since physiological mechanisms have been adapted to maximize fitness under specific temperatures. However, literature suggests that upwellings could act as thermal refugia under climate warming protecting marine ecosystem diversity. This research aimed to predict the effects of climate warming on commercial and non-commercial fish species reported in official Mexican documents (>200 species) based on their thermal niche to observe if upwellings can act as potential thermal refugia. Present (2000-2014) and Representative Concentration Pathway (6.0 and 8.5) scenarios (2040-2050 and 2090-2100) have been considered for this work. Current and future suitability patterns, species distribution, richness, and turnover were calculated using the minimum volume ellipsoids as algorithm. The results in this study highlight that beyond migration to higher latitudes, upwelling regions could protect marine fishes, although the mechanism differed between the innate characteristics of upwellings. Most modeled species (primarily tropical fishes) found refuge in the tropical upwelling in Northern Yucatan. However, the highest warming scenario overwhelmed this region. In contrast, the Baja California region lies within the Eastern Boundary Upwelling Systems. While the area experiences an increase in suitability, the northern regions have a higher upwelling intensity acting as environmental barriers for many tropical species. Conversely, in the southern regions where upwelling is weaker, species tend to congregate and persist even during elevated warming, according to the turnover analysis. These findings suggest that tropicalization in higher latitudes may not be as straightforward as previously assumed. Nevertheless, climate change affects numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. In addition, uncertainty still exists about the assumption of increasing intensity of upwelling systems.

Mobile App for Enhanced Anterior Cruciate Ligament (ACL) Assessment in Conscious Subjects: "Pivot-Shift Meter".

Anterior cruciate ligament (ACL) instability poses a considerable challenge in traumatology and orthopedic medicine, demanding precise diagnostics for optimal treatment. The pivot-shift test, a pivotal assessment tool, relies on subjective interpretation, emphasizing the need for supplementary imaging. This study addresses this limitation by introducing a machine learning classification algorithm integrated into a mobile application, leveraging smartphones' built-in inertial sensors for dynamic rotational stability assessment during knee examinations. Orthopedic specialists conducted knee evaluations on a cohort of 52 subjects, yielding valuable insights. Quantitative analyses, employing the Intraclass Correlation Coefficient (ICC), demonstrated robust agreement in both intraobserver and interobserver assessments. Specifically, ICC values of 0.94 reflected strong concordance in the timing between maneuvers, while signal amplitude exhibited consistency, with the ICC ranging from 0.71 to 0.66. The introduced machine learning algorithms proved effective, accurately classifying 90% of cases exhibiting joint hypermobility. These quantifiable results underscore the algorithm's reliability in assessing knee stability. This study emphasizes the practicality and effectiveness of implementing machine learning algorithms within a mobile application, showcasing its potential as a valuable tool for categorizing signals captured by smartphone inertial sensors during the pivot-shift test.

Immune Response to the Recombinant Apa Protein from Mycobacterium tuberculosis Expressed in Streptomyces lividans After Intranasal Administration in Mice. Induction of Protective Response to Tubercle Bacillus Aerosols Exposure.

Identifying and evaluating potential vaccine candidates has become one of the main objectives to combat tuberculosis. Among them, mannosylated Apa antigen from Mycobacterium tuberculosis and the non-mannosylated protein expressed in Escherichia coli, have been studied. Although both proteins can induce a protective response in mice, it has been considered that native protein can be dispensed. In this work, we study the protective response induced by Apa expressed in E. coli and in Streptomyces lividans. The latter, like native is secreted as a double band of 45/47 kDa, however, only its 47 kDa band is mannosylated. Both antigens and BCG were intranasal administrated in mice, and animals were then challenged by aerosol with M. tuberculosis H37Rv. The results showed that both, Apa from S. lividans and E. coli conferred statistically significantly protection to animals compared to controls. The cytokine immune response was studied by an immunoassay after animals' immunization, revealing that Apa from S. lividans induced a statistically significant proliferation of T cell, as well as the expression of IFN-γ, IL-1ß, IL-17 and IL-10. In contrast, non-proliferation was obtained with non-mannosylated protein, but induction of IL-12 and IL-17 was observed. Together, these results demonstrate that both proteins were able to modulate a specific immune response against M. tuberculosis, that could be driven by different mechanisms possibly associated with the presence or not of mannosylation. Furthermore, stimulation of cells from BCG-vaccinated animals with the proteins could be an important tool, to help define the use of a given subunit-vaccine after BCG vaccination.

FGF23 as a Potential Pathophysiological Factor in Peripheral Arterial Disease Associated with Chronic Kidney Disease.

Fibroblast growth factor 23 (FGF23) levels are often elevated in chronic kidney disease (CKD). FGF23 and inflammation are common characteristics in CKD, and both are associated with worse disease progression and the occurrence of complications. The existence of an interaction between FGF23 and inflammation has been suggested, each of which influences the expression and activity of the other, leading to a vicious feedback loop with adverse outcomes, including cardiovascular disease and mortality. In this work, we determined circulating FGF23 levels in a group of patients with CKD stages 3 and 4 subjected to elective femoral endarterectomy due to established peripheral artery disease (PAD), a condition resulting from an athero-inflammatory process, and we studied its associations with different inflammatory markers and mediators. We evaluated its association with serum tumor necrosis factor (TNF)α, interleukin (IL) 6, and IL10, as well as with the gene expression levels of these parameters and A disintegrin and metalloproteinase domain-containing protein (ADAM) 17 in femoral vascular tissue and peripheral blood circulating cells (PBCCs). We also analyzed its association with serum concentrations of C-reactive protein (CRP), the systemic immune inflammation index (SII), and the neutrophil-to-lymphocyte ratio (NLR). Finally, we determined the vascular immunoreactivity of protein TNFα in a subgroup of patients. FGF23 concentrations were independently associated with circulating and PBCC mRNA levels of TNFα. Worst kidney function and diabetes were also found to be contributing to FGF23 levels. Patients with higher levels of FGF23 also had greater vascular immunoreactivity for TNFα.

Modeling of host PDZ-dependent interactions with SARS-CoV-2 Envelope protein and changes in PDZ proteins expression in macrophages and dendritic cells.

PDZ (PSD-95/Dlg/ZO-1) domain-containing proteins constitute a large family of scaffolds involved in a wide range of cellular tasks, and mainly studied in polarity functions. Diverse host PDZ proteins can be targeted by viral pathogens which express proteins containing PDZ-binding motifs (PDZbm). Previously, we have identified host PDZ-based interactions with the SARS-CoV-2 E protein (2E) in human monocytes. Here, we deepen the study of these interactions by docking and molecular dynamics analyses to identify the most favorable PDZ-PDZbm interaction of seven host PDZ proteins with the PDZbm of 2E. In addition, we analyzed changes in the expression of three of the PDZ proteins identified as 2E interactors in monocytes (syntenin, ZO-2, and IL-16), in human monocyte-derived macrophages (MΦ) and in dendritic cells (DCs) upon stimulation. Our results suggest that these PDZ proteins may have important functions in professional antigen-presenting cells (APCs), and their targeting by the PDZbm of 2E, a central virulence determinant of SARS-CoV-2, support the hypothesis that such PDZ-dependent interaction in immune cells may constitute a viral evasion mechanism. Inhibitor design based on the PDZbm of 2E in the development of drugs against a variety of diseases is discussed.

Association between lipid profile and clinical outcomes in COVID-19 patients.

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.

Acute Kidney Injury in the Context of COVID-19: An Analysis in Hospitalized Mexican Patients.

During the COVID-19 pandemic, a considerable proportion of patients developed a severe condition that included respiratory failure, shock, or multiple organ dysfunction. Acute Kidney Injury (AKI) has been recognized as a possible cause of severe COVID-19 development. Given this, this study investigates the occurrence and consequences of AKI in Mexican patients to contribute to better knowledge and management of this problem. Methods: Using a retrospective observational cohort methodology, we investigated 313 cases from a cohort of 1019 patients diagnosed with COVID-19 at the IMSS Zacatecas General Hospital of Zone No. 1 in 2020. The prevalence of AKI was determined using the AKIN criteria based on serum creatinine levels and a detailed review of demographic characteristics, medical history, comorbidities, and clinical development. Results: The data showed a 25.30% prevalence of AKI among patients infected with severe COVID-19. Remarkably, these patients with AKI exhibited an advanced age (>65 years), arterial hypertension, a higher number of white blood cells during admission and the hospital stay, and elevated levels of C-reactive protein, serum creatinine, and blood urea nitrogen (BUN). Clinically, patients with AKI had signs of prostration, pneumonia, and the requirement for ventilatory assistance when compared to those without AKI. Finally, those diagnosed with AKI and COVID-19 had a 74% death rate. Relative risk analyses indicated that age (>65 years), arterial hypertension, high creatinine levels, endotracheal intubation, and pneumonia are associated with the development of AKI. On the other hand, among the protective factors against AKI, high hemoglobin levels and the consumption of statins during COVID-19 were found. Conclusions: The findings of this study underscore the significance of promptly identifying and effectively managing AKI to potentially alleviate the negative consequences of this complication within the Mexican population during COVID-19.

Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Biomechanical and histological comparison of two suture configurations for soft tissue grafts: speedtrap™ versus krackow stitch.

To compare 2 different graft preparation techniques to determine biomechanical strength and resultant tissue trauma evaluated by histology. Twelve common flexors of the finger's tendons were prepared with either tubulization (SpeedTrap™) or transtendon stiches (Orthocord™). The stiffness, resistance and energy at maximum load were tested for biomechanical assessment in both groups. After load testing, Samples were stained with hematoxylin and eosin (HE) to evaluate histological damage. We observe that the time to prepare tendons with SpeedTrap™ was 8.3 times faster (1:25 min) than traditional ones (15:02 min). In all cases, the mean values for SpeedTrap™ were higher in terms of strength, stiffness and energy at maximum load than for traditional suture but without significant difference (p > 0.05). The Krackow stitch produces greater structural damage to the collagen fibers while SpeedTrap™ maintains better organized arrangement of the fibers after tubulization preparation. With the results obtained, we can conclude that the tubulization technique allows faster graft preparation with less structural damage to the manipulated tissue without altering the biomechanical resistance provided by the transtendon suture technique.