Socioeconomic disparities and the genomic landscape of gastric cancer.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

Ovine dicrocoeliosis in Castellón province, eastern Spain: Prevalence, dynamics, and comparative study of different diagnostic techniques.

Dicrocoeliosis is a parasitic disease that mainly affects ruminants during grazing, caused by trematodes of the genus Dicrocoelium, with D. dendriticum being the most common species worldwide. This parasitosis is a chronic and generally subclinical process, with nonspecific signs, which makes its diagnosis challenging. This study aimed to determine the prevalence and seasonal dynamics of D. dendriticum infection in adult sheep from the Valencian Community, eastern Spain, as well as to evaluate the efficacy of flotation and sedimentation techniques when compared with the macroscopic exam of the liver. From February to May 2018, 2019, 2020, 2021, and 2022, a total of 290 adult sheep were examined. The animals were sourced from Castellón province, where a semi-intensive production system predominates. Each animal was euthanized and underwent a macroscopic examination of the liver, as well as a fecal analysis. Among the sampled animals, 117 (40.6%) tested positive for adult trematodes in their liver, while 87 (30%) showed evidence of trematode eggs in the coprological exam, reaching a total of 126 sheep parasitized, with a prevalence of 43.4%. The parasitic burden was established in 90.3 adults per animal when the liver was examined and in 54.5 eggs per gram when the sedimentation coprological exam was performed. No eggs were observed when the flotation technique was employed. A positive correlation was found between the number of adults in the liver and the fecal egg count. No significant differences were detected in the prevalence or parasitic burden throughout the study. Considering the difficulty in controlling the intermediate hosts and the complexity of the life cycle, effective diagnostic methods, combined with the adoption of other preventive measures, is crucial to achieving proper management of this parasitic disease.

Building national patient registries in Mexico: insights from the MexOMICS Consortium.

Objective: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population. Methods: Since 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists. We also acquired DNA samples and Magnetic Resonance Imaging scans in subsets of participants. Results: The registries have successfully enrolled a large number of participants from a variety of regions within Mexico: TwinsMX (n = 2,915), LupusRGMX (n = 1,761) and MEX-PD (n = 750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected DNA samples to study the genetic biomarkers across the three registries. Cognitive function has been assessed with the Montreal Cognitive Assessment in a subset of 376 MEX-PD participants. Furthermore, a subset of 267 twins have participated in cognitive evaluations with the Creyos platform and in MRI sessions acquiring structural, functional, and spectroscopy brain imaging; comparable evaluations are planned for LupusRGMX and MEX-PD. Conclusions: The MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.

Targeted and untargeted serum NMR metabolomics to reveal initial kidney disease in diabetes mellitus.

Serum 1H NMR metabolomics has been used as a diagnostic tool for screening type 2 diabetes (T2D) with chronic kidney disease (CKD) as comorbidity. This work aimed to evaluate 1H NMR data to detect the initial kidney damage and CKD in T2D subjects, through multivariate statistical analysis. Clinical data and biochemical parameters were obtained for classifying five experimental groups using KDIGO guidelines: Control (healthy subjects), T2D, T2D-CKD-mild, T2D-CKD-moderate, and T2D-CKD-severe. Serum 1H NMR spectra were recorded to follow two strategies: one based on metabolite-to-creatinine (Met/Cr) ratios as targeted metabolomics, and the second one based on untargeted metabolomics from the 1H NMR profile. A prospective biomarkers panel of the early stage of T2D-CKD based in metabolite-to-creatinine ratio (ornithine/Cr, serine/Cr, mannose/Cr, acetate/Cr, acetoacetate/Cr, formate/Cr, and glutamate/Cr) was proposed. Later, a statistical model based on non-targeted metabolomics was used to predict initial CKD, and its metabolic pathway analysis allowed identifying the most affected pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine degradation; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and histidine metabolism. Nonetheless, further studies with a larger cohort are advised to precise ranges in metabolite-to-creatinine ratios and evaluate the prediction pertinency to detect initial CKD in T2D patients in both statistical models proposed.

A cyst-forming coccidian with large geographical range infecting forest and commensal rodents: Sarcocystis muricoelognathis sp. nov.

BACKGROUND: The geographic distribution and host-parasite interaction networks of Sarcocystis spp. in small mammals in eastern Asia remain incompletely known. METHODS: Experimental infections, morphological and molecular characterizations were used for discrimination of a new Sarcocystis species isolated from colubrid snakes and small mammals collected in Thailand, Borneo and China. RESULTS: We identified a new species, Sarcocystis muricoelognathis sp. nov., that features a relatively wide geographic distribution and infects both commensal and forest-inhabiting intermediate hosts. Sarcocystis sporocysts collected from rat snakes (Coelognathus radiatus, C. flavolineatus) in Thailand induced development of sarcocysts in experimental SD rats showing a type 10a cyst wall ultrastructure that was identical with those found in Rattus norvegicus from China and the forest rat Maxomys whiteheadi in Borneo. Its cystozoites had equal sizes in all intermediate hosts and locations, while sporocysts and cystozoites were distinct from other Sarcocystis species. Partial 28S rRNA sequences of S. muricoelognathis from M. whiteheadi were largely identical to those from R. norvegicus in China but distinct from newly sequenced Sarcocystis zuoi. The phylogeny of the nuclear 18S rRNA gene placed S. muricoelognathis within the so-called S. zuoi complex, including Sarcocystis attenuati, S. kani, S. scandentiborneensis and S. zuoi, while the latter clustered with the new species. However, the phylogeny of the ITS1-region confirmed the distinction between S. muricoelognathis and S. zuoi. Moreover, all three gene trees suggested that an isolate previously addressed as S. zuoi from Thailand (KU341120) is conspecific with S. muricoelognathis. Partial mitochondrial cox1 sequences of S. muricoelognathis were almost identical with those from other members of the group suggesting a shared, recent ancestry. Additionally, we isolated two partial 28S rRNA Sarcocystis sequences from Low's squirrel Sundasciurus lowii that clustered with those of S. scandentiborneensis from treeshews. CONCLUSIONS: Our results provide strong evidence of broad geographic distributions of rodent-associated Sarcocystis and host shifts between commensal and forest small mammal species, even if the known host associations remain likely only snapshots of the true associations.

Investigating the Shared Genetic Etiology Between Parkinson's Disease and Depression.

Background: Depression is a common symptom in Parkinson's disease (PD), resulting from underlying neuropathological processes and psychological factors. However, the extent to which shared genetic risk factors contribute to the relationship between depression and PD is poorly understood. Objective: To examine the effects of common genetic variants influencing the etiology of PD and depression risk at the genome-wide and local genomic regional level. Methods: We comprehensively investigated the genetic relationship between PD and depression using genome-wide association studies data. First, we estimated the genetic correlation at the genome-wide level using linkage-disequilibrium score regression, followed by local genetic correlation analysis using the GWAS-pairwise method and functional annotation to identify genes that may jointly influence the risk for both traits. Also, we performed Latent Causal Variable, Latent Heritable Confounder Mendelian Randomization, and traditional Mendelian Randomization analyses to investigate the potential causal relationship. Results: Although the genetic correlation between PD and depression was not statistically significant at the genome-wide level, GWAS-pairwise analyses identified 16 genomic segments associated with PD and depression, implicating nine genes. Further analyses revealed distinct patterns within individual genes, suggesting an intricate pattern. These genes involve various biological processes, including neurotransmitter regulation, senescence, and nucleo-cytoplasmic transport mechanisms. We did not observe genetic evidence of causality between PD and depression. Conclusions: Our findings did not support a genome-wide genetic correlation or a causal association between both conditions. However, we identified genomic segments but identified genomic segments linked to distinct biological pathways influencing their etiology.Further research is needed to understand their functional consequences.

Endoperiodontal lesions: diagnosis first, then treatment and not always tooth extraction: a cross-sectional survey in Spain and a proposal of a clinical treatment protocol.

Background: Endoperiodontal lesion (EPL) is defined as a pathological communication between pulpal and periodontal tissues. Currently, accurate diagnosis and treatment of this pathology are challenging. This study aims to identify the different endoperiodontal therapies to propose a clinical protocol to simplify and unify the criteria for EPL treatment. Material and Methods: Observational cross-sectional study through an electronic survey. This study matches STROBE guidelines. The anonymous questionnaire contained open-ended and close-ended questions and was distributed to dentistry professors of the UPV/EHU and different professionals from Spanish associations and scientific societies. The data collected were analyzed using descriptive and analytical statistics. Results: A total of 128 responses were obtained, of which 120 were active professionals or had not been so for less than 5 years. The majority of professionals were women (65.6%) and from the Basque Country (63.9%). A total of 86.6% reported having complementary studies to a degree or a bachelor's degree. The treatments performed by these professionals were similar to those reported in the literature, which started with root canal treatment when there was an endodontic origin (91.5%), and with basic periodontal treatment when periodontal (51.3%). Conclusions: Considering the current scientific evidence and the clinical practice of professionals in the treatment of EPL, we designed a clinical protocol. This protocol needs validation in larger populations and with longer follow-ups. Key words:Clinical protocol, Dental pulp diseases, Periodontal diseases, Review, Surveys and questionnaires.

Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against Mycobacterium tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently, antimicrobial peptides have been discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 h compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, for two peptides, a strongly diminished formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Resting-state EEG signatures of Alzheimer's disease are driven by periodic but not aperiodic changes.

Electroencephalography (EEG) has shown potential for identifying early-stage biomarkers of neurocognitive dysfunction associated with dementia due to Alzheimer's disease (AD). A large body of evidence shows that, compared to healthy controls (HC), AD is associated with power increases in lower EEG frequencies (delta and theta) and decreases in higher frequencies (alpha and beta), together with slowing of the peak alpha frequency. However, the pathophysiological processes underlying these changes remain unclear. For instance, recent studies have shown that apparent shifts in EEG power from high to low frequencies can be driven either by frequency specific periodic power changes or rather by non-oscillatory (aperiodic) changes in the underlying 1/f slope of the power spectrum. Hence, to clarify the mechanism(s) underlying the EEG alterations associated with AD, it is necessary to account for both periodic and aperiodic characteristics of the EEG signal. Across two independent datasets, we examined whether resting-state EEG changes linked to AD reflect true oscillatory (periodic) changes, changes in the aperiodic (non-oscillatory) signal, or a combination of both. We found strong evidence that the alterations are purely periodic in nature, with decreases in oscillatory power at alpha and beta frequencies (AD < HC) leading to lower (alpha + beta) / (delta + theta) power ratios in AD. Aperiodic EEG features did not differ between AD and HC. By replicating the findings in two cohorts, we provide robust evidence for purely oscillatory pathophysiology in AD and against aperiodic EEG changes. We therefore clarify the alterations underlying the neural dynamics in AD and emphasize the robustness of oscillatory AD signatures, which may further be used as potential prognostic or interventional targets in future clinical investigations.

Social support in low-income women with Fibromyalgia Syndrome from a sub-urban and peri-urban areas of Tenerife (Canary Islands, Spain): a mixed method study.

BACKGROUND: Women with Fibromyalgia Syndrome (FMS) can benefit form adequate social support to fight the consequences of their illness, but the extent to which this is available to those with low incomes who live in depressed areas of Tenerife (Canary Islands, Spain) is currently unknown. The purpose of this study was to explore social support in low-incomes women with FMS in sub-urban and peri-urban areas of Tenerife. METHODOLOGY: A sequential exploratory mixed method study was carried out from January 20, 2023, to June 10, 2023, at the Fibromyalgia and Chronic Fatigue Association of Tenerife (AFITEN) using non-probability convenience sampling. Social support was analyzed quantitatively through MOS-SSS survey and Duke-UNC-11 questionnaire, while qualitative data were obtained through semi-structured interviews to identify social support providers and analyze their satisfactions levels. RESULTS: A total of 49 women, with a mean age of 57.80 years-old (SD = 13.25) were finally included in this study. MOSS-SSS and Duke-UNC-11 both indicated lower social support levels at 68.6 (SD =16.3) and 38.0 (SD = 9.74), respectively. The qualitative analysis revealed that partners and friends provided the most significant support with the highest satisfaction scores. CONCLUSIONS: The socioeconomic status of low-income women with FMS living in sub-urban and peri-urban areas of Tenerife (Canary Islands, Spain) influences on their social support, with the affective support and confidentiality being the most affected dimensions.

Specific Cationic Antimicrobial Peptides Enhance the Recovery of Low-Load Quiescent Mycobacterium tuberculosis in Routine Diagnostics.

The culture confirmation of Mycobacterium tuberculosis (MTB) remains the gold standard for the diagnosis of Tuberculosis (TB) with culture conversion representing proof of cure. However, over 40% of TB samples fail to isolate MTB even though many patients remain infectious due to the presence of viable non-culturable forms. Previously, we have shown that two short cationic peptides, T14D and TB08L, induce a hormetic response at low concentrations, leading to a stimulation of growth in MTB and the related animal pathogen Mycobacterium bovis (bTB). Here, we examine these peptides showing they can influence the mycobacterial membrane integrity and function through membrane potential reduction. We also show this disruption is associated with an abnormal reduction in transcriptomic signalling from specific mycobacterial membrane sensors that normally monitor the immediate cellular environment and maintain the non-growing phenotype. We observe that exposing MTB or bTB to these peptides at optimal concentrations rapidly represses signalling mechanisms maintaining dormancy phenotypes, which leads to the promotion of aerobic metabolism and conversion into a replicative phenotype. We further show a practical application of these peptides as reagents able to enhance conventional routine culture methods by stimulating mycobacterial growth. We evaluated the ability of a peptide-supplemented sample preparation and culture protocol to isolate the MTB against a gold standard routine method tested in parallel on 255 samples from 155 patients with suspected TB. The peptide enhancement increased the sample positivity rate by 46% and decreased the average time to sample positivity of respiratory/faecal sampling by seven days. The most significant improvements in isolation rates were from sputum smear-negative low-load samples and faeces. The peptide enhancement increased sampling test sensitivity by 19%, recovery in samples from patients with a previously culture-confirmed TB by 20%, and those empirically treated for TB by 21%. We conclude that sample decontamination and culture enhancement with D-enantiomer peptides offer good potential for the much-needed improvement of the culture confirmation of TB.

Evaluation of hypoglycemic and antioxidant effects of Brickellia eupatorioides, Citrus limettioides and Gochnatia hypoleuca.

Diabetes is a chronic metabolic condition with a rapidly increasing prevalence. It comes with a rise in the generation of free radicals, potentially leading to additional health issues. Further studies and creative approaches are required to address this. Natural products are potential new antidiabetic drugs that are worth exploring. The aim of the present study is to assess the antihyperglycemic and antioxidant effects of ethanolic extracts of Brickellia eupatorioides, Citrus limettioides and Gochnatia hypoleuca. The antihyperglycemic activity of the extracts was tested on Wistar rats (diabetes induced by alloxan, 150mg/kg), as well as the inhibitory effect on a-glucosidase and a-amylase (in vitro assay). The antioxidant potential was evaluated using DPPH and ABTS assays. The total phenolic and flavonoid contents were also determined. The results indicated that ethanolic extracts of B. eupatorioides induced a powerful hypoglycemic in vivo effect with a significant decrease at 6h after administration, similar to that produced by glibenclamide; the decrease could be related to a-glucosidase inhibition. Moreover, the extract exhibited a potent scavenging activity (IC50 values 33±6mg/mL and 15±2mg/mL in the DPPH and ABTS methods, respectively). The results demonstrated antihyperglycemic and antioxidant activity of ethanolic extracts of B. eupatorioides.

Uso de TIC ́s para el manejo de enfermedades cardiovasculares / Use of ICTs for the managem ent of cardiovascular diseases

¿Son efectivas las aplicaciones móviles en las personas adultas con enfermedades cardiovasculares para mejorar su control? Como es sabido la población de edad más avanzada considera un obstáculo determinante el avance de la sociedad y su adaptación a los cambios que involucra, lo que refiere la importancia de buscar nuevas herramientas que le faciliten esa adaptación, aún más cuando su salud depende de ello cuando deben enfrentarse al control de enfermedades crónicas y de mucha atención. En este artículo se responderá esta interrogante mediante la revisión bibliográfica sistemática bajo estrategias de búsqueda en bases de datos reconocidas como Pubmed y Scielo de artículos previos enfocados al uso de TIC's en el control de enfermedades. Rescatando finalmente 6 artículos que muestran resultados positivos en la mejora del estado de salud y/o de la ad-herencia al tratamiento de los pacientes controlados en sus estudios, discutiendo factores que podrían mejorar sus resultados en estudios en los que no fueron significativos, valorando limitaciones y recomendaciones para estudios futuros, invitando finalmente a la población, a mejorar el estudio de la población adulta y adulta mayor, y a la búsqueda de herramientas que le permitan mejorar su salud, así como en el caso de las TIC'S que son una gran ayuda para mejorar el control de éstas, al comprobar que no generan ningún riesgo para quien las utiliza, no interfiere con la terapia tradicional farmacológica y solo refiere beneficios a pesar de las limitantes de accesibilidad que pueden ser fácilmente controladas[AU]

Are mobile applications effective in adults with cardiovascular diseases to improve their control? As is known, the older population considers the progress of society and its adaptation to the changes it involves to be a determining obstacle, which refers to the importance of seeking new tools that facilitate this adaptation, even more so when their health depends on This is when they have to face the control of chronic diseases and a lot of care. This article will answer this question through a systematic bibliographic review using search strategies in recognized databases such as Pubmed and Scielo of previous articles focused on the use of ICTs in disease control. Finally rescuing 6 articles that show positive results in improving the state of health and/or adherence to treatment of patients controlled in their studies, discussing factors that could improve their results in studies in which they were not significant, assessing limitations and recommendations for future studies, finally inviting the population to improve the study of the adult and elderly population, and to search for tools that allow them to improve their health, as well as in the case of ICTs that are a great help to improve the control of these, by verifying that they do not generate any risk for those who use them, does not interfere with traditional pharmacological therapy and only refers benefits despite the accessibility limitations that can be easily controlled[AU]

Os aplicativos móveis são eficazes em adultos com doenças cardio-vasculares para melhorar seu controle? Como se sabe, a população idosa considera o progresso da sociedade e sua adaptação às mu-danças que ela envolve um obstáculo determinante, o que remete à importância de buscar novas ferramentas que facilitem essa adap-tação, ainda mais quando sua saúde depende de quando têm que enfrentar o controle de doenças crônicas e muito cuidado. Este arti-go responderá a esta questão por meio de uma revisão bibliográfica sistemática utilizando estratégias de busca em bases de dados re-conhecidas como Pubmed e Scielo de artigos anteriores focados no uso das TICs no controle de doenças. Por fim resgatando 6 artigos que mostram resultados positivos na melhora do estado de saúde e/ou adesão ao tratamento dos pacientes controlados em seus estu-dos, discutindo fatores que poderiam melhorar seus resultados em estudos em que não foram significativos, avaliando limitações e re-comendações para estudos futuros, convidando finalmente a popu-lação a melhorar o estudo da população adulta e idosa, e a procurar ferramentas que lhes permitam melhorar a sua saúde, bem como no caso das TIC que são uma grande ajuda para melhorar o controlo destas, por verificando que não geram nenhum risco para quem os utiliza, não interferem na terapia farmacológica tradicional e ape-nas remetem a benefícios, apesar das limitações de acessibilidade facilmente controláveis[AU]

Hepatodamianol as hepatoprotective constituent of Turnera diffusa.

It is well known that liver diseases are a major health problem and that there is a lack of hepatoprotective agents. Turnera diffusa (damiana) is a plant with a widespread distribution in México, which has many traditional uses, including the treatment of hepatic illnesses. Based on the bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, we purified and identified a compound called hepatodamianol (1). This C-glycoside exhibited a four times greater hepatoprotective effect than the widely used hepatoprotective agent silibinin against carbon tetrachloride damage in an in vitro model using HepG2 cells. Hepatodamianol produced no cytotoxic effects and it exhibited a high antioxidant capacity. Therefore, hepatodamianol is a good candidate compound for testing as a hepatoprotective agent in a preclinical trial.

Discovery of Antimicrobial Peptides That Can Accelerate Culture Diagnostics of Slow-Growing Mycobacteria Including Mycobacterium tuberculosis.

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses, and parasites. At sublethal concentrations, some AMPs and also conventional antibiotics can stimulate bacterial response increasing their resilience, also called the hormetic response. This includes stimulation of growth, mobility, and biofilm production. Here, we describe the discovery of AMPs that stimulate the growth of certain mycobacteria. Peptide 14 showed a growth stimulating effect on Mycobacteria tuberculosis (MTB), M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum, and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering stationary phase when compared to nontreated controls. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For MTB, a collection of 25 artificial peptides were screened and 13 were found to reduce the time to positivity (TTP) by at least 5%, improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the database APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, and the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment were the most active fragments of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 10 ng/mL and 10 µg/mL, whereas the stability-optimised Peptide 14D had a narrow activity range of 0.1-1 µg/mL. Peptides identified in this study are currently in commercial use to improve recovery and culture for the diagnostics of mycobacteria in humans and animals.

MEX-PD: A National Network for the Epidemiological & Genetic Research of Parkinson's Disease.

Background: Parkinson's Disease (PD) has a complex etiology, involving genetic and environmental factors. Most of our current understanding of the disease comes from studies in populations with mostly European ancestry, representing challenges in generalizing findings to other populations with different genetic, social, and environmental contexts. There are scarce studies focused in Latin American populations. The Mexican population is genetically diverse because its admixture from Native American, European, and African ancestries, coupled with the unique environmental conditions, stressing the relevance of establishing genetic studies in this population. Thus, we have established the Mexican Parkinson's Research Network (MEX-PD), a consortium to research the clinical, genetical, environmental, and neurophysiological bases of the phenotypic diversity in Mexican PD patients. Objectives: Describing how MEX-PD was established, the methods and instruments and presenting the first results. Methods: Patients and controls were recruited from medical centers in 20 states of Mexico. Initial recruitment included neurological evaluation, cognitive assessment, and DNA collection. Results: MEX-PD has registered 302 controls and 262 PD patients with a mean age of diagnosis of 61 years (SD=10.86). There were 19.8% PD patients identified with early onset. Levodopa was the most common pharmacological treatment. Conclusions: MEX-PD contributes to understand PD nationally. The information gathered here will allow us to understand the prevalence of mental health, neurological symptoms, and cognitive function in the PD Mexican population and how genetical and environmental factors contributes to those outcomes. These will advocate for personalized treatments and improving quality of life in the Mexican population.

Can BioSAXS detect ultrastructural changes of antifungal compounds in Candida albicans?-an exploratory study.

The opportunistic yeast Candida albicans is the most common cause of candidiasis. With only four classes of antifungal drugs on the market, resistance is becoming a problem in the treatment of fungal infections, especially in immunocompromised patients. The development of novel antifungal drugs with different modes of action is urgent. In 2016, we developed a groundbreaking new medium-throughput method to distinguish the effects of antibacterial agents. Using small-angle X-ray scattering for biological samples (BioSAXS), it is now possible to screen hundreds of new antibacterial compounds and select those with the highest probability for a novel mode of action. However, yeast (eukaryotic) cells are highly structured compared to bacteria. The fundamental question to answer was if the ultrastructural changes induced by the action of an antifungal drug can be detected even when most structures in the cell stay unchanged. In this exploratory work, BioSAXS was used to measure the ultrastructural changes of C. albicans that were directly or indirectly induced by antifungal compounds. For this, the well-characterized antifungal drug Flucytosine was used. BioSAXS measurements were performed on the synchrotron P12 BioSAXS beamline, EMBL (DESY, Hamburg) on treated and untreated yeast C. albicans. BioSAXS curves were analysed using principal component analysis (PCA). The PCA showed that Flucytosine-treated and untreated yeast were separated. Based on that success further measurements were performed on five antifungal peptides {1. Cecropin A-melittin hybrid [CA (1-7) M (2-9)], KWKLFKKIGAVLKVL; 2. Lasioglossin LL-III, VNWKKILGKIIKVVK; 3. Mastoparan M, INLKAIAALAKKLL; 4. Bmkn2, FIGAIARLLSKIFGKR; and 5. optP7, KRRVRWIIW}. The ultrastructural changes of C. albicans indicate that the peptides may have different modes of action compared to Flucytosine as well as to each other, except for the Cecropin A-melittin hybrid [CA (1-7) M (2-9)] and optP7, showing very similar effects on C. albicans. This very first study demonstrates that BioSAXS shows promise to be used for antifungal drug development. However, this first study has limitations and further experiments are necessary to establish this application.

Resting-state EEG signatures of Alzheimer's disease are driven by periodic but not aperiodic changes.

Electroencephalography (EEG) has shown potential for identifying early-stage biomarkers of neurocognitive dysfunction associated with dementia due to Alzheimer's disease (AD). A large body of evidence shows that, compared to healthy controls (HC), AD is associated with power increases in lower EEG frequencies (delta and theta) and decreases in higher frequencies (alpha and beta), together with slowing of the peak alpha frequency. However, the pathophysiological processes underlying these changes remain unclear. For instance, recent studies have shown that apparent shifts in EEG power from high to low frequencies can be driven either by frequency specific periodic power changes or rather by non-oscillatory (aperiodic) changes in the underlying 1/f slope of the power spectrum. Hence, to clarify the mechanism(s) underlying the EEG alterations associated with AD, it is necessary to account for both periodic and aperiodic characteristics of the EEG signal. Across two independent datasets, we examined whether resting-state EEG changes linked to AD reflect true oscillatory (periodic) changes, changes in the aperiodic (non-oscillatory) signal, or a combination of both. We found strong evidence that the alterations are purely periodic in nature, with decreases in oscillatory power at alpha and beta frequencies (AD < HC) leading to lower (alpha + beta) / (delta + theta) power ratios in AD. Aperiodic EEG features did not differ between AD and HC. By replicating the findings in two cohorts, we provide robust evidence for purely oscillatory pathophysiology in AD and against aperiodic EEG changes. We therefore clarify the alterations underlying the neural dynamics in AD and emphasise the robustness of oscillatory AD signatures, which may further be used as potential prognostic or interventional targets in future clinical investigations.

Effectiveness of physical therapy interventions in women with dyspareunia: a systematic review and meta-analysis.

BACKGROUND: Dyspareunia is defined as the occurrence of pain during or after sexual intercourse, which directly affects physical, sexual, and mental health. This condition can lead to depression, anxiety, and low self-esteem in women who experience it. OBJECTIVES: The aim of this research was to evaluate the effectiveness of physical therapy interventions for the treatment of female dyspareunia. DESIGN: A systematic review and meta-analysis was conducted. METHOD: Search of publications was conducted in Scopus, Medline, Pubmed, Cinahl and Web of Science. Treatment effects were defined as standardized mean difference and their 95% confidence intervals. Statistical heterogeneity was assessed using Crohan's Q test and quantified using the I2 index. RESULTS: Of the 19 articles selected, six applied multimodal physiotherapy treatments; five, electrotherapy; three, Thiele's massage; two, interdisciplinary interventions or pelvic floor muscle training; and one, extracorporeal shockwave therapy. The meta-analysis showed significant results for the variables pain and quality of life with the interventions based on electrotherapy and electrotherapy combined with pelvic floor muscle training. These interventions did not show significant results for the improvement of sexual function. CONCLUSIONS: Physiotherapy techniques are effective and procedures have been identified with reliable results in improving pain and quality of life in patients with dyspareunia. One of the most important aspects is the strengthening of the perineal musculature and the application of Transcutaneous Electrical Nerve Stimulation. Furthermore, manual trigger point release therapy and Thiele massage, optimize and guarantee the reduction of pain intensity. PROSPERO REGISTRATION: CRD42021236155.