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.

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.

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.

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.

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.

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.

Dermatoglyphic Profiles of Competitive Athletes: CrossFit and Ultra-Marathon / Perfiles Dermatoglíficos de Deportistas Competitivos: CrossFit y Ultramaratón

SUMMARY: In the sports field, sports are usually classified according to the predominance of the energy system used during the competition; sports like Crossfit and ultra-marathon could be totally opposite due to the needs of athletes to achieve good places. Due to the above, the objective was established to compare the dermatoglyphic profiles of CrossFit and Ultra-marathon athletes according to the predisposition of the energy systems, aerobic and anaerobic, used in the competitions. Cross-sectional descriptive study, where the dermatoglyphic profile of 21 athletes of national presence (10 crossfit and 11 ultra-marathon runners) was determined, through the Computerized Dermatoglyphic System, brand Salus Dermatoglifia, according to the Cummins and Midlo protocol, which consists of taking the fingerprints of the 10 fingers of the hands. The fingerprint designs of the human being (arch, loop and whorl) and the elements contained in them (nucleus and delta) were analyzed, differences were established through the Analysis of Variance test in the SPSS V.25 statistical package. The results show significant differences between the average scores of the line count of both disciplines (108 and 165), being higher in ultra-marathon runners, associated with greater aerobic resistance. Another significant and relevant finding was the presence of arch-type fingerprints only in CrossFit athletes associated, along with low line count, with strength and power. It is concluded that Crossfit and Ultra-marathon athletes have dissimilar natural physical characteristics, which is why they participate and excel in different sports where they have enhanced their natural physical abilities through training.

En el ámbito deportivo, los deportes suelen clasificarse según el predominio del sistema energético utilizado durante la competición; Deportes como el Crossfit y la ultramaratón podrían ser totalmente opuestos debido a las necesidades de los deportistas de conseguir buenos lugares. Debido a lo anterior, se estableció como objetivo comparar los perfiles dermatoglíficos de atletas de CrossFit y Ultramaratón según la predisposición de los sistemas energéticos, aeróbico y anaeróbico, utilizados en las competencias. Estudio descriptivo transversal, donde se determinó el perfil dermatoglífico de 21 deportistas de presencia nacional (10 crossfit y 11 ultramaratonistas), a través del Sistema Dermatoglífico Computarizado, marca Salus Dermatoglifia, según el protocolo Cummins y Midlo, el cual consta de tomando las huellas dactilares de los 10 dedos de las manos. Se analizaron los diseños dactilares del ser humano (arco, asa y verticilo) y los elementos contenidos en ellos (núcleo y delta), se establecieron diferencias mediante la prueba de Análisis de Varianza en el paquete estadístico SPSS V.25. Los resultados muestran diferencias significativas entre las puntuaciones medias del recuento de líneas de ambas disciplinas (108 y 165), siendo superiores en los corredores de ultramaratón, asociado a una mayor resistencia aeróbica. Otro hallazgo significativo y relevante fue la presencia de huellas dactilares tipo arco sólo en atletas de CrossFit asociadas, junto con un bajo número de líneas, con fuerza y potencia. Se concluye que los atletas de Crossfit y Ultramaratón tienen características físicas naturales disímiles, por lo que participan y destacan en diferentes deportes donde han potenciado sus capacidades físicas naturales a través del entrenamiento.

Correlational study of ergonomic knowledge and level of MSK discomfort during online classes of 1st-4th year UST-CRS physical therapy students: a cross-sectional study.

INTRODUCTION: The abrupt transition of the mode of learning due to the COVID-19 pandemic resulted in an increase in complaints of musculoskeletal (MSK) discomfort among students in Higher Education Institutions (HEI). Inadequate physical space and equipment are one major cause of these complaints. Among HEIs, physical therapy (PT) students have sufficient background in managing MSK discomforts. However, this does not prevent them from experiencing pain and discomfort during online classes. This analytical cross-sectional study aims to determine the correlation between ergonomic knowledge and MSK discomfort among first-year to fourth-year PT students. METHODS AND ANALYSIS: The study will use two questionnaires, the Ergonomic Knowledge Questionnaire, and the Cornell Musculoskeletal Discomfort Questionnaire, that determine the level of ergonomic knowledge and MSK discomfort, respectively. This will be disseminated to 144 students through google forms. Results will then be analysed using Pearson Correlation Test. The study anticipates a correlation between the level of ergonomic knowledge and MSK discomfort among the participants. ETHICS AND DISSEMINATION: The study has been approved by the University of Santo Tomas-College of Rehabilitation Sciences Ethics Review Committee. The participants will receive the results prior to publication in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: Philippine Health Research Registry with registry ID PHRR230216-005443.

Use of biochar and a post-coagulation effluent as an adsorbent of malachite green, beneficial bacteria carrier, and seedling substrate for plants belonging to the poaceae family.

Wastewater treatment plants produce solid and semi-solid sludge, which treatment minimises secondary environmental pollution because of wastewater treatment and obtaining new bioproducts. For this reason, in this paper, the co-pyrolysis of biogenic biomasses recovered from a biological reactor with immobilised fungal and bacterial biomass and a tertiary reactor with Chlorella sp. used for dye-contaminated wastewater treatment was carried out. Biogenic biomasses mixed with pine bark allowed the production and characterisation of two types of biochar. The raw material and biochar were on the "in vitro" germination of Lolium sp. seeds, followed by adsorption studies for malachite green (MG) dye using the raw material and the biochar. Results showed that using 60 mg L-1 of a cationic coagulant at pH 6.5 allowed for the recovery of more than 90% of the microalgae after 50 min of processing. Two biochar resulted: BC300, at pH 5.08 ± 0.08 and BC500, at pH 6.78 ± 0.01. The raw material and both biochars were co-inoculated with growth-promoting bacteria; their viabilities ranged from 1.7 × 106 ± 1.0 × 101 to 7.5 × 108 ± 6.0 × 102 CFU g-1 for total heterotrophic, nitrogen-fixing and phosphate-solubilising bacteria. Re-use tests on Lolium sp. seed germination showed that with the post-coagulation effluent, the germination was 100%, while with the biochar, with and without beneficial bacteria, the germination was 98 and 99%, respectively. Finally, BC500 adsorbed the highest percentage of malachite green at pH 4.0, obtaining qecal values of 0.5249 mg g-1 (R2: 0.9875) with the pseudo-second-order model. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03766-x.

Aqueous Fraction from Cucumis sativus Aerial Parts Attenuates Angiotensin II-Induced Endothelial Dysfunction In Vivo by Activating Akt.

BACKGROUND: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. METHODS: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were injected daily with angiotensin II (Ang-II) for 10 weeks. Once hypertension was established, either Cs-AqC4 or losartan was orally administered along with Ang-II for a further 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. In addition, serum creatinine, inflammatory status (in the kidney), tissue damage, and vascular remodeling (in the liver and aorta) were evaluated. Cs-AqC4 was also tested in vitro on HMEC-1 cells stimulated by Ang-II to assess the involvement of Akt phosphorylation. RESULTS: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1ß and TGF-ß, increased IL-10, and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. CONCLUSIONS: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension; it also improved tissue damage associated with ED, probably via Akt activation.

The frequency of complications in a cohort of patients diagnosed with hemophilia A and hemophilia B receiving prophylactic treatment in Colombia: A retrospective noninterventional study.

INTRODUCTION: Hemophilia A and B are disorders associated with the deficit of coagulation factors VIII and IX. OBJECTIVE: Was to determine the incidence of complications in a cohort of patients diagnosed with moderate and severe hemophilia A or B under treatment in a specialized institution. METHODS: A retrospective study of a cohort of patients with replacement therapy for hemophilia A or B, evaluating treatment and complications between January/2012 and July/2019. Sociodemographic, clinical and disease management-related variables were extracted from the medical records. Time to inhibitor development and rate associated with bleeding and hospitalizations were evaluated. RESULTS: A total of 159 male patients were identified with hemophilia A (n = 140; 88.1%) and B (n = 19; 11.9%) with a mean follow-up of 5.9±2.3 years. The mean age was 23.6±16.1 years, hemophilia was reported as severe in 125 patients in hemophilia A (89.3%) and 13 patients in hemophilia B (68.4%). Primary prophylaxis was registered in 17.0% of patients, 44.7% secondary, and 38.3% tertiary, with recombinant factors (n = 84; 52.8%) followed by plasma derived factors (n = 75; 47.2%). The incidence of inhibitor development was 0.3 per 100 patients/year, with mean time to event of 509 days. The incidence of bleeding was 192 per 100 patients/year, especially at the joint (n = 99; 62.3%) and muscle (n = 25; 15.7%) level. The incidence of hospitalization was 3.7 per 100 patients/year. CONCLUSIONS: The most common complication was joint bleeding which was expected in this type of patients. Low proportion of patients developed factor inhibitors during the follow up.

The enzymes of the oxidative phase of the pentose phosphate pathway as targets of reactive species: consequences for NADPH production.

The pentose phosphate pathway (PPP) is a key metabolic pathway. The oxidative phase of this process involves three reactions catalyzed by glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL) and 6-phosphogluconate dehydrogenase (6PGDH) enzymes. The first and third steps (catalyzed by G6PDH and 6PGDH, respectively) are responsible for generating reduced nicotinamide adenine dinucleotide phosphate (NAPDH), a key cofactor for maintaining the reducing power of cells and detoxification of both endogenous and exogenous oxidants and electrophiles. Despite the importance of these enzymes, little attention has been paid to the fact that these proteins are targets of oxidants. In response to oxidative stimuli metabolic pathways are modulated, with the PPP often up-regulated in order to enhance or maintain the reductive capacity of cells. Under such circumstances, oxidation and inactivation of the PPP enzymes could be detrimental. Damage to the PPP enzymes may result in a downward spiral, as depending on the extent and sites of modification, these alterations may result in a loss of enzymatic activity and therefore increased oxidative damage due to NADPH depletion. In recent years, it has become evident that the three enzymes of the oxidative phase of the PPP have different susceptibilities to inactivation on exposure to different oxidants. In this review, we discuss existing knowledge on the role that these enzymes play in the metabolism of cells, and their susceptibility to oxidation and inactivation with special emphasis on NADPH production. Perspectives on achieving a better understanding of the molecular basis of the oxidation these enzymes within cellular environments are given.

Solvent-Assisted Laser Desorption Flexible Microtube Plasma Mass Spectrometry for Direct Analysis of Dried Samples on Paper.

The present study investigated the potential for solvent-assisted laser desorption coupled with flexible microtube plasma ionization mass spectrometry (SALD-FµTP-MS) as a rapid analytical technique for direct analysis of surface-deposited samples. Paper was used as the demonstrative substrate, and an infrared hand-held laser was employed for sample desorption, aiming to explore cost-effective sampling and analysis methods. SALD-FµTP-MS offers several advantages, particularly for biofluid analysis, including affordability, the ability to analyze low sample volumes (<10 µL), expanded chemical coverage, sample and substrate stability, and in situ analysis and high throughput potential. The optimization process involved exploring the use of viscous solvents with high boiling points as liquid matrices. This approach aimed to enhance desorption and ionization efficiencies. Ethylene glycol (EG) was identified as a suitable solvent, which not only improved sensitivity but also ensured substrate stability during analysis. Furthermore, the addition of cosolvents such as acetonitrile/water (1:1) and ethyl acetate further enhanced sensitivity and reproducibility for a standard solution containing amphetamine, imazalil, and cholesterol. Optimized conditions for reproducible and sensitive analysis were determined as 1000 ms of laser exposure time using a 1 µL solvent mixture of 60% EG and 40% acetonitrile (ACN)/water (1:1). A mixture of 60% EG and 40% ACN/water (1:1) resulted in signal enhancements and relative standard deviations of 12, 20, and 13% for the evaluated standards, respectively. The applicability of SALD-FµTP-MS was further evaluated by successfully analyzing food, water, and biological samples, highlighting the potential of SALD-FµTP-MS analysis, particularly for thermolabile and polarity diverse compounds.

Oxidative damage associated with exposure to heavy metals present in topsoils in central Chile.

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.

Case Report: Characterization of known (c.607G>C) and novel (c.416C>G) ELANE mutations in two Mexican families with congenital neutropenia.

The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family.

Testicular Evaluation Using Shear Wave Elastography (SWE) in Patients with Varicocele.

PURPOSE: To assess the possible influence of the presence of varicocele on the quantification of testicular stiffness. METHODS: Ultrasound with shear wave elastography (SWE) was performed on 48 consecutive patients (96 testicles) referred following urology consultation for different reasons. A total of 94 testes were studied and distributed in three groups: testes with varicocele (group A, n = 19), contralateral normal testes (group B; n = 13) and control group (group C, n = 62). Age, testicular volume and testicular parenchymal tissue stiffness values of the three groups were compared using the Kruskal-Wallis test. RESULTS: The mean age of the patients was 42.1 ± 11.1 years. The main reason for consultation was infertility (64.6%). The mean SWE value was 4 ± 0.4 kPa (kilopascal) in group A, 4 ± 0.5 kPa in group B and 4.2 ± 0.7 kPa in group C or control. The testicular volume was 15.8 ± 3.8 mL in group A, 16 ± 4.3 mL in group B and 16.4 ± 5.9 mL in group C. No statistically significant differences were found between the three groups in terms of age, testicular volume and tissue stiffness values. CONCLUSION: Tissue stiffness values were higher in our control group (healthy testicles) than in patients with varicocele.