Pre- versus Post-synaptic Forms of LTP in Two Branches of the Same Hippocampal Afferent.

There has been considerable controversy about pre- versus postsynaptic expression of memory-related long-term potentiation (LTP), with corresponding disputes about underlying mechanisms. We report here an instance in male mice, in which both types of potentiation are expressed but in separate branches of the same hippocampal afferent. Induction of LTP in the dentate gyrus (DG) branch of the lateral perforant path (LPP) reduces paired-pulse facilitation, is blocked by antagonism of cannabinoid receptor type 1, and is not affected by suppression of postsynaptic actin polymerization. These observations are consistent with presynaptic expression. The opposite pattern of results was obtained in the LPP branch that innervates the distal dendrites of CA3: LTP did not reduce paired-pulse facilitation, was unaffected by the cannabinoid receptor blocker, and required postsynaptic actin filament assembly. Differences in the two LPP termination sites were also noted for frequency facilitation of synaptic responses, an effect that was reproduced in a two-step simulation by small adjustments to vesicle release dynamics. These results indicate that different types of glutamatergic neurons impose different forms of filtering and synaptic plasticity on their afferents. They also suggest that inputs are routed to, and encoded by, different sites within the hippocampus depending upon the pattern of activity arriving over the parent axon.

Marginalization and tooth loss in older Mexican adults.

OBJECTIVE: To examine the association between the level of marginalization and tooth loss in adults aged ≥50 years in Mexico. METHODS: A retrospective cross­sectional study was conducted on 2098 adults selected from communities presenting both high and medium levels of marginalization, with data obtained from the annual reports of the Epidemiological Surveillance System of Oral Pathologies 2019-2022. Analysis considered sociodemographic characteristics such as sex, age, and years of education. The prevalence of tooth loss was determined using the Decayed, Missing and Filled teeth (DMFT) index. Negative binomial regression was used to estimate rate ratio (RR) and 95% confidence intervals (CIs), using the presence of lost teeth as an outcome. RESULTS: Most (62.4%) participants had lost at least one tooth, of whom 60.3% had a medium level of marginalization, 28.8% a high level, and 10.9% a very high level. More adults who lived in high or very high marginalization communities had lost teeth [RR=1.19 (95% CI 1.08 - 1.30)] than those living in communities with a medium level of marginalization. More males [RR=1.19 (95% CI 1.09 - 1.31)], adults ≥70 years [RR=1.77 (95% CI 1.57 - 1.99)], people who were illiterate [RR=1.60 (95% CI 1.35 - 1.88)] or who had poor oral hygiene [RR=1.26 (95% CI 1.15 - 1.38)] had also lost teeth. CONCLUSION: High and very high marginalization was associated with tooth loss in adults ≥50 years in Mexico. Effective oral health strategies are required to prevent tooth loss, as are interventions to improve access to and quality of dental services for marginalized communities.

Validation of a sub-epidermal moisture scanner for early detection of pressure ulcers in an ex vivo porcine model of localized oedema.

Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.

Dynamical response of a rocking rigid block.

This paper investigates the complex dynamical behavior of a rigid block structure under harmonic ground excitation, thereby mimicking, for instance, the oscillation of the system under seismic excitation or containers placed on a ship under periodic acting of sea waves. The equations of motion are derived, assuming a large frictional coefficient at the interface between the block and the ground, in such a way that sliding cannot occur. In addition, the mathematical model assumes a loss of kinetic energy when an impact with the ground takes place. The resulting mathematical model is then formulated and studied in the framework of impulsive dynamical systems. Its complex dynamical response is studied in detail using two different approaches, based on direct numerical integration and path-following techniques, where the latter is implemented via the continuation platform COCO (Dankowicz and Schilder). Our study reveals the presence of various dynamical phenomena, such as branching points, fold and period-doubling bifurcation of limit cycles, symmetric and asymmetric periodic responses, and chaotic motions. By using the basin stability method, we also investigate the properties of solutions and their ranges of existence in phase and parameter spaces. Moreover, the study considers ground excitation conditions leading to the overturning of the block structure and shows parameter regions wherein such behavior can be avoided.

Perineurioma versus meningioma. A multi-institutional immunohistochemical and ultrastructural studY.

The differential diagnosis between perineurioma (PN) and meningioma (MEN) can be difficult by histology and immunohistochemistry (IHC) because the perineurium and arachnoid have the same embryological origin. However, there are no comparative studies determining conclusive parameters for the differential diagnosis. The aim of this study is to compare IHC of PN and MEN and their ultra-structural characteristics to elucidate which are the useful data that allow differentiate both entities. Thirty-five MEN were analyzed, and 15 PN, (11 skin and soft tissues and four oral cavity). IHC for epithelial membrane antigen (EMA), Claudin-1, GLUT-1, somatostatin-2 receptor (SSTR-2), and progesterone receptor (RP) was performed. Ultrastructural studies were performed on 8 MEN and 15 PN. Only in PN Claudin-1 was positive in 9/11 (90%) cases and GLUT-1 in 7/11 (63%) cases. In MEN, the progesterone receptor was expressed in 21/35 (60%) cases and no case expressed Claudin-1 and GLUT-1; EMA was expressed in all MEN cases and 93% of PN. SSTR-2 was expressed weakly in six cases of MEN (17%), and it was not considered useful for differential diagnosis. On ultrastructure, PN showed thin and parallel processes, some caveolae, and lacked cell junctions. The cellular processes were surrounded by a collagenous stroma in 94% of the cases. MEN were characterized by curved cytoplasmic cell processes showing desmosomes in 75% of cases. Ultrastructural findings aid in the differential diagnosis between PN and MEN, especially if molecular studies are not available.

Bactericidal and fungicidal capacity of Ag2O/Ag nanoparticles synthesized with Aloe vera extract.

This research aims to provide an alternative eco-friendly way to obtain silver species and assess their bactericidal activity. This study reports the synthesis of Ag2O nanoparticles and Ag nanoparticles reduced with a green synthesis method, using a low-cost and commercial Aloe vera extract. The crystalline phases of Ag and Ag2O nanoparticles were analyzed by X-ray diffraction. The oxidation states for both species were determined by X-ray photoelectron spectroscopy. The optical properties of the material were studied through optical absorption, which resulted in well-defined band centered at 545 nm. This result is attributed to the morphology and size of the silver nanoparticles. In addition, antibacterial tests were performed on AgNPs biosynthesized with A. vera with the Kirby-Bauer protocol on Gram-negative and Gram-positive bacteria Escherichia coli and Staphylococcus aureaus, respectively. Moreover, antifungal tests were performed with various species from Candida.

Niemann-Pick disease type-B: a unique case report with compound heterozygosity and complicated lipid management.

BACKGROUND: Niemann-Pick disease (NPD) is a rare autosomal recessive hereditary disease characterized by deficient activity of acid sphingomyelinase. CASE PRESENTATION: We present a case of NPD type B with a unique compound heterozygosity for SMPD1 (NM_000543.4:c.[84delC];[96G > A]) in which both mutations that induce an early stop codon are located before the second in-frame initiation codon. The clinical presentation of the patient is compatible with NPD type B. She was initially diagnosed of Gaucher Disease, but her altered lipid profile led to a clinical suspicion of NPD. Combined high doses of atorvastatin and ezetimibe were given to treat the severe hypercholesterolemia. CONCLUSIONS: The pharmacological management of the lipid profile in these patients is important. A unique compound mutation in SMPD1 gene is described.

PLGA nanoparticles of a new cinnamic acid derivative inhibits cellular proliferation on breast cancer cell line MCF-7 in a PPARγ dependent way.

Currently, cancer treatments are highly invasive, and they have been associated with a lot of adverse effects that put patient integrity at risk. Therefore, research of novel molecules and delivery systems capable of achieving a therapeutic effect that modifies inhibits and reduces the proliferative activity in cancer cells and, at the same time, reduce adverse effects associated with conventional therapies is imperative. In this study, we analyzed the biological effect of a novel cinnamic acid derivative, 3,4-dichlorobencil-p-phenoxylcilamide, in polymeric nanoparticles over MCF-7 breast cancer cells. The nanoparticulated system showed an inhibitory influence over cellular metabolism at equal or higher concentrations than 25 µM of 3,4-dichlorobencil-p-phenoxylcilamide, which is associated with PPARγ transcriptional activity, in addition to the decrease in the proliferation antigen Ki-67 basal levels. Those results position this kind of nanoscale system as an alternative on breast cancer treatment and lay the basis for research on the action mechanism associated with its cellular metabolism modulation and relationship with another hallmark on breast cancer cellular models.

Pharmacokinetic variations of nimesulide in mongrel dogs according to age.

The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6 months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but, the dosing regimens in humans should be different when administered at early age.

Hippocampal sclerosis induced in mice by a Taenia crassiceps metacestode factor.

An experimental Taenia crassiceps mouse model was used to assess the role of Taenia solium metacestode factor (Fac) in human neurocysticercosis. Intraperitoneal infection with T. crassiceps metacestodes or subcutaneous inoculation with a T. crassiceps metacestode factor (Fac) produced significant impairment of performance (learning) in the Barnes maze and induced bilateral hippocampal sclerosis in mice. Several staining techniques revealed important cell dispersion, extensive apoptosis and cell loss in the dentate gyrus, hilus and CA1-CA3 regions of both hippocampi, as well as intense deterioration of the adjacent cortex. An outstanding disruption of its histoarchitecture in the surrounding tissue of all these regions and apoptosis of the endothelial cells were also observed.

Mutant p53 gain of function induces HER2 over-expression in cancer cells.

BACKGROUND: HER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of HER2-amplifying tumors carry germline mutations of p53. The mechanisms responsible for the acquisition of oncogenic functions of p53 mutant proteins (mtp53), known as Gain of Function (GOF), over HER2 expression have not been reported. The objective of this study was to evaluate a possible relationship between p53 mutants and HER2 regulation. METHODS: HER2 expression (transcription and protein), as well as HER2 protein stabilization have been evaluated after inducing or silencing of p53 mutants' expression in cell lines. Finally, we evaluated the interaction of the p53 mutants over the HER2 receptor promoter. RESULTS: Higher HER2 expression in cell lines harboring endogenous mtp53 compared with wt or null expression of p53 cell lines. Transfection of p53 mutants (R248Q and R273C) in cell lines increased the expression of HER2. Silencing of p53 mutants, decrease HER2 expression. The p53 mutants R248Q and R273C significantly increase the luciferase activity on the HER2 promoter, and both mutants also promote acetylation of H3 and H4 histones binding in it. CONCLUSIONS: These findings show for the first time that p53 mutants induce over-expression of HER2 at transcriptional level of the HER2 protein. Our results could have clinical implications in breast cancer and other types of cancer where HER2 is over-expressed and used as a therapy target.

Signatures of co-evolutionary host-pathogen interactions in the genome of the entomopathogenic nematode Steinernema carpocapsae.

BACKGROUND: The entomopathogenic nematode Steinernema carpocapsae has been used worldwide as a biocontrol agent for insect pests, making it an interesting model for understanding parasite-host interactions. Two models propose that these interactions are co-evolutionary processes in such a way that equilibrium is never reached. In one model, known as "arms race", new alleles in relevant genes are fixed in both host and pathogens by directional positive selection, producing recurrent and alternating selective sweeps. In the other model, known as"trench warfare", persistent dynamic fluctuations in allele frequencies are sustained by balancing selection. There are some examples of genes evolving according to both models, however, it is not clear to what extent these interactions might alter genome-level evolutionary patterns and intraspecific diversity. Here we investigate some of these aspects by studying genomic variation in S. carpocapsae and other pathogenic and free-living nematodes from phylogenetic clades IV and V. RESULTS: To look for signatures of an arms-race dynamic, we conducted massive scans to detect directional positive selection in interspecific data. In free-living nematodes, we detected a significantly higher proportion of genes with sites under positive selection than in parasitic nematodes. However, in these genes, we found more enriched Gene Ontology terms in parasites. To detect possible effects of dynamic polymorphisms interactions we looked for signatures of balancing selection in intraspecific genomic data. The observed distribution of Tajima's D values in S. carpocapsae was more skewed to positive values and significantly different from the observed distribution in the free-living Caenorhabditis briggsae. Also, the proportion of significant positive values of Tajima's D was elevated in genes that were differentially expressed after induction with insect tissues as compared to both non-differentially expressed genes and the global scan. CONCLUSIONS: Our study provides a first portrait of the effects that lifestyle might have in shaping the patterns of selection at the genomic level. An arms-race between hosts and pathogens seems to be affecting specific genetic functions but not necessarily increasing the number of positively selected genes. Trench warfare dynamics seem to be acting more generally in the genome, likely focusing on genes responding to the interaction, rather than targeting specific genetic functions.

Acaricidal activity of Metarhizium anisopliae isolated from paddocks in the Mexican tropics against two populations of the cattle tick Rhipicephalus microplus.

The acaricidal effects of 55 strains of Metarhizium anisopliae (Metschnikoff) Sorokin, 1883 (Hypocreales: Clavicipitaceae) isolated from paddocks of cattle farms were evaluated in two Rhipicephalus microplus (Canestrini 1887) (Ixodida: Ixodidae) populations, of which one was multi-resistant and one was susceptible to chemical acaricides. Percentage mortality and reproductive efficiency indices in R. microplus were evaluated by adult immersion tests at a dose of 1 × 108 conidia/mL for each fungal strain. Some strains were selected to calculate lethal concentrations to kill 50% (LC50 ) and 99% (LC99 ) of engorged ticks. Strains MaV22, MaV26 and MaV55 induced 100% mortality in R. microplus on day 14. Strains MaV05, MaV09 and MaV22 caused mortality of >90% from day 12 onward in both tick populations. The most effective acaricidal fungal strain, MaV55, inhibited egg laying by 54.86 and 55.86% in acaricide-resistant and -susceptible R. microplus populations, respectively. None of the fungal strains had statistically significant effects on larval hatching. In conclusion, nine strains of M. anisopliae demonstrated high acaricidal effects against R. microplus and reduced its egg laying. No differences in acaricidal effects were observed between the two populations of ticks tested.

Fermentation of Dietetic Fiber from Green Bean and Prickly Pear Shell by Pure and Mixture Culture of Lactobacillus acidophilus LA-5 and Bifidobacterium bifidum 450B.

The aim of this study was to evaluate the fermentation of dietary fiber from green bean (Phaseolus vulgaris) and prickly pear shell (Opuntia ficus-indica) by Lactobacillus acidophilus LA-5 and Bifidobacterium bifidum 450B growing as mono-culture and co-culture, the fermentation products, and proteins expressed during this process. The analysis of the fermentation profile showed a major growth of bacteria in the culture media of each dietary fiber supplemented with glucose, and particularly B. bifidum 450B at 48 h showed the highest growth. In the case of the co-culture, the growth was lower indicating the possible negative interaction between L. acidophilus LA-5 and B. bifidum 450B and may be due to the less amount of carbohydrates and the high content of non-soluble fiber that affected the nutrients availability for the bacterial strains. The pH changes indicated the presence of short-chain fatty acids (SCFAs), being acetate (46-100%) the main SCFA. Changes in the proteome concerned proteins that are involved in carbohydrate and other carbohydrate pathways. The characterization of the bacteria according to the growth, metabolites, and proteins expressed allows understanding the response to the change of environmental conditions and could be useful to understand L. acidophilus LA-5 and B. bifidum 450B strains' adaptation to specific applications.

Apoptosis of mouse hippocampal cells induced by Taenia crassiceps metacestode factor.

Seizures, headache, depression and neurological deficits are the signs and symptoms most frequently reported in human neurocysticercosis. However, the cause of the associated learning and memory deficits is unknown. Here, we used Taenia crassiceps infection in mice as a model of human cysticercosis. The effects of T. crassiceps metacestode infection or T. crassiceps metacestode factor (MF) treatment on mouse hippocampal cells were studied; control mice were included. At 45 days after infection or treatment of the mice with MF, all mice were anaesthetized and perfused transcardially with saline followed by phosphate-buffered 10% formalin. Then the brains were carefully removed. Coronal sections stained using several techniques were analysed. Extensive and significant apoptosis was found in the experimental animals, mainly in the dentate gyrus, CA1, CA2, CA3 and neighbouring regions, in comparison with the apparently intact cells from control mice (P < 0.01). These results suggest that neurological deficits, especially the learning and memory deficits, may be generated by extensive apoptosis of hippocampal cells.

Carbonic anhydrases and their functional differences in human and mouse sperm physiology.

Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm.

Musculoskeletal evaluation in severe haemophilia A patients from Latin America.

There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL(-1) ) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long-term prophylaxis. Overall, 143 patients (5-66 years of age) were enrolled from nine countries. In countries where long-term prophylaxis had been available for at least 10 years (Group A), patients aged 5-10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where long-term prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of long-term prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated.

Patient satisfaction and quality of life following laparoscopic Nissen fundoplication.

BACKGROUND: Today, antireflux surgery has an established position in the management of gastroesophageal reflux disease. Some case series have shown good short-term results, but there is still little information regarding long-term results. Studies have recently focused on evaluating residual symptomatology and its impact on quality of life. OBJECTIVES: To determine the postoperative quality of life and degree of satisfaction in patients that underwent laparoscopic Nissen fundoplication. PATIENTS AND METHODS: A total of 100 patients (59 women and 41 men) were studied after having undergone laparoscopic Nissen fundoplication. The variables analyzed were level of satisfaction, gastrointestinal quality of life index (GIQLI), residual symptoms, and the Visick scale. RESULTS: No variation was found in relation to sex; 49 men and 51 women participated in the study. The mean age was 49 years. The degree of satisfaction encountered was: satisfactory in 81 patients, moderate in 3, and bad in 2 patients. More than 90% of the patients would undergo the surgery again or recommend it. The Carlsson score showed improvement at the end of the study (p<0.05). In relation to the GIQLI, a median of 100.61 points±21.624 was obtained. Abdominal bloating, regurgitation, and early satiety were the most frequent residual symptoms. The effect on lifestyle measured by the Visick scale was excellent. CONCLUSIONS: The level of satisfaction and quality of life obtained were comparable with reported standards; and the residual symptoms after antireflux surgery were easily controlled.