Disruptions in the food supply chain: A literature review.

Disruptions in the food supply chain are events that affect the flow of products and can be caused by extreme weather, natural disasters, conflicts, pandemics, and political situations, among others. These events can significantly impact food products' availability, quality, and cost, creating risks to the well-being of local populations and livelihoods. The specific literature on food supply chains needs to address other approaches to risk categorisation, which allow for establishing reference frameworks focused on the general classification of types of disruption and parameters related to solution methods. In this paper, we present a literature review to analyse the disruptions in the food supply chain. We classified 74 papers according to the types of disruptions, stakeholders, response level, supply chain echelon, solution methods, goals, and related considerations. The review results showed that the most common disruptions in the food supply chain are climatic, biological and environmental, logistics and infrastructure, and supply. The results of this review allow us to suggest some new research directions.

Low-cost heat assisted ambient ionization source for mass spectrometry in food and pharmaceutical screening.

Ambient Ionization Mass Spectrometry (AI-MS) techniques have revolutionized analytical chemistry by enabling rapid analysis of samples under atmospheric conditions with minimal to no preparation. In this study, the optimization of a cold atmospheric plasma for the analysis of food and pharmaceutical samples, liquid and solid, using a Heat-Assisted Dielectric Barrier Discharge Ionization (HA-DBDI) source is described. A significant enhancement in analyte signals was observed when a heating element was introduced into the design, potentially allowing for greater sensitivity. Furthermore, the synergy between the inlet temperature of the mass spectrometer and the heating element allows for precise control over the analytical process, leading to improved detection sensitivity and selectivity. Incorporating computational fluid dynamic (CFD) simulations into the study elucidated how heating modifications can influence gas transport properties, thereby facilitating enhanced analyte detection and increased signal intensity. These findings advance the understanding of HA-DBDI technology and provide valuable insights for optimizing AI-MS methodologies for a wide range of applications in food and pharmaceutical analysis.

Interneuron diversity in the human dorsal striatum.

Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations. We have also delineated the correspondence of our taxonomy with previous standardized classifications and shown the main transcriptomic and class abundance differences between caudate nucleus and putamen. Notably, based on key functional genes such as ion channels and synaptic receptors, we found matching known mouse interneuron populations for the most abundant populations, the recently described PTHLH and TAC3 interneurons. Finally, we were able to integrate other published datasets with ours, supporting the generalizability of this harmonized taxonomy.

Lack of cellular prion protein causes Amyloid ß accumulation, increased extracellular vesicle abundance, and changes to exosome biogenesis proteins.

Alzheimer's disease (AD) progression is closely linked to the propagation of pathological Amyloid ß (Aß), a process increasingly understood to involve extracellular vesicles (EVs), namely exosomes. The specifics of Aß packaging into exosomes remain elusive, although evidence suggests an ESCRT (Endosomal Sorting Complex Required for Transport)-independent origin to be responsible in spreading of AD pathogenesis. Intriguingly, PrPC, known to influence exosome abundance and bind oligomeric Aß (oAß), can be released in exosomes via both ESCRT-dependent and ESCRT-independent pathways, raising questions about its role in oAß trafficking. Thus, we quantified Aß levels within EVs, cell medium, and intracellularly, alongside exosome biogenesis-related proteins, following deletion or overexpression of PrPC. The same parameters were also evaluated in the presence of specific exosome inhibitors, namely Manumycin A and GW4869. Our results revealed that deletion of PrPC increases intracellular Aß accumulation and amplifies EV abundance, alongside significant changes in cellular levels of exosome biogenesis-related proteins Vps25, Chmp2a, and Rab31. In contrast, cellular expression of PrPC did not alter exosomal Aß levels. This highlights PrPC's influence on exosome biogenesis, albeit not in direct Aß packaging. Additionally, our data confirm the ESCRT-independent exosome release of Aß and we show a direct reduction in Chmp2a levels upon oAß challenge. Furthermore, inhibition of opposite exosome biogenesis pathway resulted in opposite cellular PrPC levels. In conclusion, our findings highlight the intricate relationship between PrPC, exosome biogenesis, and Aß release. Specifically, they underscore PrPC's critical role in modulating exosome-associated proteins, EV abundance, and cellular Aß levels, thereby reinforcing its involvement in AD pathogenesis.

Competitive oxidation of key pentose phosphate pathway enzymes modulates the fate of intermediates and NAPDH production.

The oxidative phase of the pentose phosphate pathway (PPP) involving the enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), and 6-phosphogluconate dehydrogenase (6PGDH), is critical to NADPH generation within cells, with these enzymes catalyzing the conversion of glucose-6-phosphate (G6P) into ribulose-5-phosphate (Ribu5-P). We have previously studied peroxyl radical (ROO•) mediated oxidative inactivation of E. coli G6PDH, 6PGL, and 6PGDH. However, these data were obtained from experiments where each enzyme was independently exposed to ROO•, a condition not reflecting biological reality. In this work we investigated how NADPH production is modulated when these enzymes are jointly exposed to ROO•. Enzyme mixtures (1:1:1 ratio) were exposed to ROO• produced from thermolysis of 100 mM 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). NADPH was quantified at 340 nm, and protein oxidation analyzed by liquid chromatography with mass spectrometric detection (LC-MS). The data obtained were rationalized using a mathematical model. The mixture of non-oxidized enzymes, G6P and NADP+ generated ∼175 µM NADPH. Computational simulations showed a constant decrease of G6P associated with NADPH formation, consistent with experimental data. When the enzyme mixture was exposed to AAPH (3 h, 37 °C), lower levels of NADPH were detected (∼100 µM) which also fitted with computational simulations. LC-MS analyses indicated modifications at Tyr, Trp, and Met residues but at lower concentrations than detected for the isolated enzymes. Quantification of NADPH generation showed that the pathway activity was not altered during the initial stages of the oxidations, consistent with a buffering role of G6PDH towards inactivation of the oxidative phase of the pathway.

Cytotoxic effects on human dental pulp stem Cells after exposure to adhesive bonding agents.

Studies regarding cytotoxic effects attributed to the use of adhesive bonding agents on pulp tissue are not conclusive. To point out whether these materials are safe for clinical use, in vivo exposure of dental pulp to adhesive bonding agents was simulated using an experimental setup in which Human Dental Pulp Stem Cells (hDPSC) are exposed to the action of two kinds of adhesives: self-etching adhesives and two-step bonding agents through a dentine barrier. Cytotoxic effects on these cells were evaluated by MTT assay protocol and fluorescence microscopy, and their results were contrasted to those obtained through Raman spectra taken on single hDPSCs. Overall, no significant cytotoxic effects were observed by combining all the techniques, and cell viability close to 90% was achieved for a dentine barrier of at least 1 mm thick. Moreover, Raman spectroscopy was able to detect structural DNA damage in some dental pulp cells when exposed to two-step bonding agents, suggesting that this technique could be considered a complementary tool with the potential to evaluate cell toxicity beyond cell viability.

Nonylphenol releases arachidonic acid in rat Sertoli cells via activation of PKA and PLA2.

In brief: The endocrine disruptor, nonylphenol (NP) increases 20:4n-6 release in Sertoli cells via PKA/cPLA2 activation. Our data show that lipid metabolism could be a target of NP-induced abnormal reproductive outcomes. Abstract: Nonylphenol (NP), an endocrine-disrupting chemical, is an environmental contaminant, and many notorious effects on male fertility have been reported in animal models and wild-type species. Here, we evaluated the effects of NP in follicle-stimulating hormone (FSH) signal transduction pathways and lipid metabolism using an in vitro model of rat Sertoli cell (SC) primary culture. Results show that an acute (1 h) SC exposure to NP (10 µM) increased the intra- and extra-cellular concentrations of free fatty acids (FFAs), mainly arachidonic acid (20:4n-6). Phosphatidylinositol seemed to be the major phospholipid source of this 20:4n-6 release by activation of the protein kinase A (PKA)/cytoplasmic phospholipase A2 (cPLA2) pathway. NP also increased diacylglycerols (DAG) levels and the expression (mRNA) of cyclooxygenase 2 (Cox2) and prostaglandin E2 (PGE2) levels. It is noteworthy that accumulation of lipid droplets took place after 24 h NP exposition, which was prevented by both a PKA inhibitor and a PLA2 inhibitor. Like FSH, NP triggers the release of 20:4n-6, which is a substrate for PGE2 synthesis via PKA/PLA2 activation. In addition, NP induces the formation of DAG, which could be required as a cofactor of the PKC-mediated activation of the COX2 inflammatory pathway. Our findings suggest that NP alters lipid homeostasis in SCs by inducing the activation of pro-inflammatory pathways that may trigger adverse effects in testis physiology over time. Concomitantly, the SC enhances the acylation of surplus FFAs (including 20:4n-6) in neutral lipids as a protective mechanism to shield itself from lipotoxicity and pro-inflammatory signals.

Respiratory disease patterns in rural Western Uganda, 2019-2022.

Introduction: Respiratory disease is a major cause of morbidity and mortality in the developing world, but prospective studies of temporal patterns and risk factors are rare. Methods: We studied people in rural Western Uganda, where respiratory disease is pervasive. We followed 30 adults (ages 22-51 years; 534 observations) and 234 children (ages 3-11 years; 1,513 observations) between May 2019 and July 2022 and collected monthly data on their respiratory symptoms, for a total of 2,047 case records. We examined associations between demographic and temporal factors and respiratory symptoms severity. Results: The timing of our study (before, during, and after the emergence of COVID-19) allowed us to document the effects of public health measures instituted in the region. Incidence rates of respiratory symptoms before COVID-19 lockdown were 568.4 cases per 1,000 person-months in children and 254.2 cases per 1,000 person-months in adults. These rates were 2.6 times higher than the 2019 global average for children but comparable for adults. Younger children (ages 3-6 years) had the highest frequencies and severities of respiratory symptoms. Study participants were most likely to experience symptoms in February, which is a seasonal pattern not previously documented. Incidence and severity of symptoms in children decreased markedly during COVID-19 lockdown, illustrating the broad effects of public health measures on the incidence of respiratory disease. Discussion: Our results demonstrate that patterns of respiratory disease in settings such as Western Uganda resemble patterns in developed economies in some ways (age-related factors) but not in others (increased incidence in children and seasonal pattern). Factors such as indoor air quality, health care access, timing of school trimesters, and seasonal effects (rainy/dry seasons) likely contribute to the differences observed.

Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Occurrence and risk assessment of pesticides and their transformation products related to olive groves in surface waters of the Guadalquivir river basin.

Pesticides are considered one of the main sources of contamination of surface waters, especially in rural areas highly influenced by traditional agricultural practices. The objective of this work was to evaluate the impact caused by pesticides and their transformation products (TPs) related to olive groves in surface waters with strong agricultural pressure. 11 streams were monitored during four sampling campaigns over 2 years. A solid-phase extraction, followed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) analysis was used in the quantitative target approach, with more than 70 validated compounds. Target method was combined with a suspect screening strategy involving more than 500 pesticides and TPs, using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) to identify additional pesticides and TPs out of the scope of analysis. A total of 43 different compounds were detected with the target method. The herbicide MCPA was present in all samples and at the highest concentration (1260 ng L-1), followed by the fungicide carbendazim (1110 ng L-1), and the herbicide chlorotoluron (706 ng L-1). The suspect screening strategy revealed the presence of 7 compounds out of the target analysis (1 pesticide and 6 TPs). 6 analytes were confirmed with the analytical standards. Semi-quantification results revealed that TPs exhibited higher concentrations than their corresponding parent compounds, indicating higher persistency. Some small streams showed a comparable number of pesticides and concentrations to the most polluted large river. The determined pesticide and TPs concentrations represented an estimated environmental hazard in almost all sampling sites under study. This work underscores the importance of including pesticide TPs and small streams impacted by extensive agricultural activities in water quality monitoring programs.

Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia.

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.

Miniaturized flexible micro-tube plasma ionization source for the effective ionization of non-easily ionizable pesticides in food with liquid chromatography/mass spectrometry.

In this article, we have studied the potential of flexible microtube plasma (FµTP) as ionization source for the liquid chromatography high-resolution mass spectrometry detection of non-easily ionizable pesticides (viz. nonpolar and non-ionizable by acid/basic moieties). Phthalimide-related compounds such as dicofol, dinocap, o-phenylphenol, captan, captafol, folpet and their metabolites were studied. Dielectric barrier discharge ionization (DBDI) was examined using two electrode configurations, including the miniaturized one based on a single high-voltage (HV) electrode and a virtual ground electrode configuration (FµTP), and also the two-ring electrode DBDI configuration. Different ionization pathways were observed to ionize these challenging, non-easily ionizable nonpolar compounds, involving nucleophilic substitutions and proton abstraction, with subtle differences in the spectra obtained compared with APCI. An average sensitivity increase of 5-fold was attained compared with the standard APCI source. In addition, more tolerance with matrix effects was observed in both DBDI sources. The importance of the data reported is not just limited to the sensitivity enhancement compared to APCI, but, more notably, to the ability to effectively ionize nonpolar, late-eluting (in reverse-phase chromatography) non-ionizable compounds. Besides o-phenylphenol ([M - H]-), all the parent species were efficiently ionized through different mechanisms involving bond cleavages through the effect of plasma reagent species or its combination with thermal degradation and subsequent ionization. This tool can be used to figure out overlooked nonpolar compounds in different environmental samples of societal interest through non-target screening (NTS) strategies.

Asociación del consumo de drogas ilícitas en mujeres embarazadas y sífilis congénita en un Hospital Público de México / Association of illicit drug use in pregnant women and congenital syphilis in a public hospital in Mexico

Resumen Realizamos un estudio de casos y controles anidado en una cohorte con el objetivo de estudiar la asociación del consumo de drogas ilícitas y sífilis congénita (SC). Los casos se diagnosticaron mediante pruebas treponémicas y no treponémicas en la madre y el recién nacido (RN). Se realizó un análisis multivariado con regresión logística. Se registraron 6.171 nacimientos con edad gestacional promedio 37,8 semanas y se diagnosticaron 62 eventos de SC (incidencia: 10,5 eventos/1.000 RN). Los factores maternos asociados fueron el uso de drogas ilícitas (OR = 14,08; IC 95% = 1,19-166,6), menos de cinco consultas en el control prenatal (OR = 2,9; IC 95% = 1,12-7,53), más de dos parejas sexuales (OR = 3,76; IC 95% = 1,62-8,71) y estudios universitarios (OR = 0,06; IC 95% = 0,005-0,85). Entre las madres de los casos, la prevalencia del consumo de drogas ilícitas fue de 22,6% y las más frecuentes fueron las metanfetaminas y la marihuana.

Abstract We conducted a nested case-control study within a cohort with the aim of studying the association between illicit drug use and congenital syphilis (CS). Cases were diagnosed based on treponemal and non-treponemal tests conducted both in the mother and the newborn (NB). Multivariate analysis with logistic regression was performed. A total of 6171 births with a mean gestational age of 37.8 weeks were recorded and 62 CS events were diagnosed (incidence 10.5 events/1000 NB). Associated maternal factors were illicit drug use (OR 14.08, 95% CI 1.19-166.6), <5 prenatal visits (OR 2.9, 95% CI 1.12-7.53), more than two sexual partners (OR 3.76, 95% CI 1.62-8.71) and professional education level (OR 0.06, 95% CI 0.005-0.85). Among the mothers of the cases presented, the prevalence of illicit drug use was 22.6% and the most frequent drugs were methamphetamines and cannabis.

Enhanced Compound Analysis Using Reactive Paper Spray Mass Spectrometry: Leveraging Schiff Base Reaction for Amino Acid Detection.

Paper spray mass spectrometry (PS-MS) has evolved into a promising tool for monitoring reactions in thin films and microdroplets, known as reactive PS, alongside its established role in ambient and direct ionization. This study addresses the need for rapid, cost-effective methods to improve analyte identification in biofluids by leveraging reactive PS-MS in clinical chemistry environments. The technique has proven effective in derivatizing target analytes, altering hydrophobicity to enhance elution and ionization efficiency, and refining detection through thin-film reactions on paper, significantly expediting reaction rates by using amino acids (AAs) as model analytes. These molecules are prone to interacting with substrates like paper, impeding elution and detection. Additionally, highly abundant species in biofluids, such as lipids, often suppress AA ionization. This study employs the Schiff base (SB) reaction utilizing aromatic aldehydes for AA derivatization to optimize reaction conditions time, temperature, and catalyst presence and dramatically increasing the conversion ratio (CR) of formed SB. For instance, using leucine as a model AA, the CR surged from 57% at room temperature to 89% at 70 °C, with added pyridine during and after 7.5 min, displaying a 43% CR compared to the bulk reaction. Evaluation of various aromatic aldehydes as derivatization agents highlighted the importance of specific oxygen substituents for achieving higher conversion rates. Furthermore, diverse derivatization agents unveiled unique fragmentation pathways, aiding in-depth annotation of the target analyte. Successfully applied to quantify AAs in human and rat plasma, this reactive PS-MS approach showcases promising potential in efficiently detecting conventionally challenging compounds in PS-MS analysis.

Descending necrotizing mediastinitis: key points to reduce the high associated mortality in a consecutive case series.

Background: Descending necrotizing mediastinitis (DNM) is an acute life-threatening infection that originates in the oropharyngeal region. It is an uncommon disease with a mortality rate of about 20-40%. This high mortality is mainly attributed to delays in diagnosis and treatment and poor drainage of the mediastinum. We highlight key points that may help reduce mortality. Case Description: We analyze a retrospective case series of seven patients diagnosed with DNM between March 2019 and July 2022 at Hospital de la Santa Creu i Sant Pau. The primary oropharyngeal infection was peritonsillar abscess in three cases and odontogenic abscess in four. All patients showed symptoms of severe cervical infection and symptoms suggestive of mediastinitis. A cervicothoracic computed tomography (CT) scan confirmed the presence of cervical and mediastinal collections and emphysema in all cases. All patients were simultaneously evaluated by the otorhinolaryngology and thoracic surgery teams. Broad-spectrum antibiotic therapy was instituted pending culture. All the patients underwent urgent surgery, consisting of cervicotomy to control the cervical focus and unilateral or bilateral video-assisted thoracoscopic debridement and drain of the pleural cavities and mediastinum. Regarding the outcomes, no patients died, one patient (14.2%) underwent transcervical mediastino-thoracoscopy drainage only. In six patients (85.8%) we performed a combined transcervical and transthoracic approach. Reoperation was required in 3 (43%) cases. The parameter that indicated a poor clinical evolution in these patients was an increase in C-reactive protein and the infection extension on the cervicothoracic CT scan. The follow-up was 30 days from last surgery; there were no losses. Conclusions: Based on our experience, the key points that can help reduce the high mortality associated with DNM are a rapid multidisciplinary assessment and a combined surgical procedure, considering the minimally invasive approach as the first option to drain the pleural cavities and mediastinum.

Are the minimally invasive techniques the new gold standard in thymus surgery for myasthenia gravis? Experience of a reference single-site in VATS thymectomy.

The thymus is the primary lymphoid organ responsible for the maturation and proliferation of T lymphocytes. During the first years of our lives, the activation and inactivation of T lymphocytes occur within the thymus, facilitating the correct maturation of central immunity. Alterations in the positive and negative selection of T lymphocytes have been studied as the possible origins of autoimmune diseases, with Myasthenia Gravis (MG) being the most representative example. Structural alterations in the thymus appear to be involved in the initial autoimmune response observed in MG, leading to the consideration of thymectomy as part of the treatment for the disease. However, the role of thymectomy in MG has been a subject of controversy for many years. Several publications raised doubts about the lack of evidence justifying thymectomy's role in MG until 2016 when a randomized study comparing thymectomy via sternotomy plus prednisone versus prednisone alone was published in the New England Journal of Medicine (NEJM). The results clearly favored the group of patients who underwent surgery, showing improvements in symptoms, reduced corticosteroid requirements, and fewer recurrences over 3 years of follow-up. In recent years, the emergence of less invasive surgical techniques has made video-assisted or robotic-assisted thoracoscopic (VATS/RATS) thymectomy more common, replacing the traditional sternotomy approach. Despite the increasing use of VATS, it has not been validated as a technique with lower morbidity compared to sternotomy in the treatment of MG. The results of the 2016 trial highlighted the benefits of thymectomy, but all the patients underwent surgery via sternotomy. Our hypothesis is that VATS thymectomy is a technique with lower morbidity, reduced postoperative pain, and shorter postoperative hospital stays than sternotomy. Additionally, VATS offers better clinical improvement in patients with MG. The primary objective of this study is to validate the VATS technique as the preferred approach for thymectomy. Furthermore, we aim to analyze the impact of VATS thymectomy on symptoms and corticosteroid dosage in patients with MG, identifying factors that may predict a better response to surgery.

[Association of illicit drug use in pregnant women and congenital syphilis in a public hospital in Mexico]. / Asociación del consumo de drogas ilícitas en mujeres embarazadas y sífilis congénita en un Hospital Público de México.

We conducted a nested case-control study within a cohort with the aim of studying the association between illicit drug use and congenital syphilis (CS). Cases were diagnosed based on treponemal and non-treponemal tests conducted both in the mother and the newborn (NB). Multivariate analysis with logistic regression was performed. A total of 6171 births with a mean gestational age of 37.8 weeks were recorded and 62 CS events were diagnosed (incidence 10.5 events/1000 NB). Associated maternal factors were illicit drug use (OR 14.08, 95% CI 1.19-166.6), <5 prenatal visits (OR 2.9, 95% CI 1.12-7.53), more than two sexual partners (OR 3.76, 95% CI 1.62-8.71) and professional education level (OR 0.06, 95% CI 0.005-0.85). Among the mothers of the cases presented, the prevalence of illicit drug use was 22.6% and the most frequent drugs were methamphetamines and cannabis.

Cytotoxic effects on human dental pulp stem Cells after exposure to adhesive bonding agents

Abstract Studies regarding cytotoxic effects attributed to the use of adhesive bonding agents on pulp tissue are not conclusive. To point out whether these materials are safe for clinical use, in vivo exposure of dental pulp to adhesive bonding agents was simulated using an experimental setup in which Human Dental Pulp Stem Cells (hDPSC) are exposed to the action of two kinds of adhesives: self-etching adhesives and two-step bonding agents through a dentine barrier. Cytotoxic effects on these cells were evaluated by MTT assay protocol and fluorescence microscopy, and their results were contrasted to those obtained through Raman spectra taken on single hDPSCs. Overall, no significant cytotoxic effects were observed by combining all the techniques, and cell viability close to 90% was achieved for a dentine barrier of at least 1 mm thick. Moreover, Raman spectroscopy was able to detect structural DNA damage in some dental pulp cells when exposed to two-step bonding agents, suggesting that this technique could be considered a complementary tool with the potential to evaluate cell toxicity beyond cell viability.

Resumo Os estudos sobre os efeitos citotóxicos atribuídos ao uso de agentes de união adesivo no tecido pulpar não são conclusivos. Para determinar se esses materiais são seguros para uso clínico, a exposição in vivo da polpa dentária a agentes de união adesiva foi simulada por meio de uma configuração experimental na qual as células-tronco da polpa dentária humana (hDPSC) são expostas à ação de dois tipos de adesivos: adesivos autocondicionantes e agentes de união de duas etapas por meio de uma barreira de dentina. Os efeitos citotóxicos nessas células foram avaliados pelo protocolo de ensaio MTT e microscopia de fluorescência, e seus resultados foram contrastados com os obtidos por meio de espectros Raman obtidos em hDPSCs individuais. De modo geral, não foram observados efeitos citotóxicos significativos com a combinação de todas as técnicas, e a viabilidade celular próxima a 90% foi obtida para uma barreira de dentina de pelo menos 1 mm de espessura. Além disso, a espectroscopia Raman foi capaz de detectar danos estruturais ao DNA em algumas células da polpa dentária quando expostas a agentes de colagem de duas etapas, sugerindo que essa técnica poderia ser considerada uma ferramenta complementar com potencial para avaliar a toxicidade celular além da viabilidade celular.