Esterification of dextran by octenyl succinic anhydride (OSA): Physicochemical characterization and functional properties assessment.

The chemical modification of biopolymers to enhance their functional properties in the food, cosmetic, and pharmaceutical industries is an area of particular interest today. In this study, different molecular weight dextrans were chemically modified for the first time with octenyl succinic anhydride (OSA). This reaction involves an esterification process wherein the hydroxy groups of dextran are partially substituted by a carbonaceous chain, imparting hydrophobic properties to dextran molecules and, consequently, an amphiphilic nature. To assess and quantify the incorporation of OSA into the dextran structure, reaction products were analysed using NMR and FTIR. Additionally, the thermal properties, the Z-potential and the foaming and emulsifying capacity of both native and modified dextrans were examined. The introduction of OSA groups to dextran molecules, with degrees of substitution between 0.028 and 0.058, increased the zeta potential and the thermal stability of the polymer. Furthermore, the chemical modification of dextran backbone with this radical conferred a hydrophobic nature to the biopolymer, which enhance its foaming and emulsifying capacity. Therefore, these results demonstrate that the incorporation of hydrophobic moieties into dextran polymers improves their functional properties and broadens their potential applications in the industry.

Empowering Voices: Inspiring Women in Medicinal Chemistry.

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists. The responses and contributions highlight their passions and motivations, such as their love of the sciences and their drive to improve human health by contributing to basic research and creating lifesaving drugs.

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

INTRODUCTION: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. AIMS: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. MATERIAL AND METHODS: This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. RESULTS/DISCUSSION: All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.

Empowering Voices: Inspiring Women in Medicinal Chemistry.

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists. The responses and contributions highlight their passions and motivations, such as their love of the sciences and their drive to improve human health by contributing to basic research and creating lifesaving drugs.

Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas.

INTRODUCTION: Molecular tests can contribute to improve the preoperative diagnosis of thyroid nodules. Tests available are expensive and not adapted to different populations. AIM: This study aimed to compare the cyto-histological genetic profile and to evaluate the reliability of molecular tests using ultrasound-guided fine needle aspiration cytology (US-FNAC) in accurately diagnosing differentiated thyroid carcinomas (DTCs) and predicting biologic behavior of papillary thyroid carcinomas (PTCs). MATERIALS AND METHODS: The series included 259 patients with paired cyto-histological samples totaling 518 samples. The genetic alterations were analyzed via PCR/Sanger sequencing. The association with clinicopathologic features was evaluated in PTCs. RESULTS/DISCUSSION: From the 259 patients included, histologies were 50 (19.3%) benign controls and 209 (80.7%) DTC cases, from which 182 were PTCs; cytologies were 5.8% non-diagnostic, 18.2% benign, 39% indeterminate, and 37.1% malignant. In histology, indeterminate nodules (n = 101) were 22.8% benign and 77.2% malignant. Mutation frequencies in cytology and histology specimens were, respectively, TERTp: 3.7% vs. 7.9%; BRAF: 19.5% vs. 25.1%; and RAS: 11% vs. 17.5%. The overall cyto-histological agreement of the genetic mutations was 94.9%, with Cohen's k = 0.67, and in indeterminate nodules agreement was 95.7%, k = 0.64. The identified mutations exhibited a discriminative ability in diagnosing DTC with a specificity of 100% for TERTp and BRAF, and of 94% for RAS, albeit with low sensitivity. TERTp and BRAF mutations were associated with aggressive clinicopathological features and tumor progression in PTCs (p < 0.001). The obtained good cyto-histological agreement suggests that molecular analysis via US-FNAC may anticipate the genetic profile and the behavior of thyroid tumors, confirming malignancy and contributing to referring patients to surgery.

Phage Lytic Protein CHAPSH3b Encapsulated in Niosomes and Gelatine Films.

Antimicrobial resistance (AMR) has emerged as a global health challenge, sparking worldwide interest in exploring the antimicrobial potential of natural compounds as an alternative to conventional antibiotics. In recent years, one area of focus has been the utilization of bacteriophages and their derivative proteins. Specifically, phage lytic proteins, or endolysins, are specialized enzymes that induce bacterial cell lysis and can be efficiently produced and purified following overexpression in bacteria. Nonetheless, a significant limitation of these proteins is their vulnerability to certain environmental conditions, which may impair their effectiveness. Encapsulating endolysins in vesicles could mitigate this issue by providing added protection to the proteins, enabling controlled release, and enhancing their stability, particularly at temperatures around 4 °C. In this work, the chimeric lytic protein CHAPSH3b was encapsulated within non-ionic surfactant-based vesicles (niosomes) created using the thin film hydrating method (TFH). These protein-loaded niosomes were then characterized, revealing sizes in the range of 30-80 nm, zeta potentials between 30 and 50 mV, and an encapsulation efficiency (EE) of 50-60%. Additionally, with the objective of exploring their potential application in the food industry, these endolysin-loaded niosomes were incorporated into gelatine films. This was carried out to evaluate their stability and antimicrobial efficacy against Staphylococcus aureus.

Communicating Risks and Food Procedures through a Visual Poster for Caregivers of Patients with Dysphagia in Inpatient Care: Usability and Impact.

Food-related procedures are a part of rehabilitation interventions for dysphagia. However, studies show that professional-caregiver communication is often lacking in dysphagia, risking caregivers' knowledge, understanding, and practice of those procedures, with negative consequences for patient safety and rehabilitation. The aim of this study was to evaluate caregivers' perspectives about the utility of a poster designed to communicate dysphagia-related risks and food procedures for caregivers of patients in inpatient care. The impact of caregivers' exposure to the poster on patients' dysphagia-related health was additionally explored. The poster was placed by the beds of a randomly assigned group of patients (n = 21). Their caregivers responded to a questionnaire about the poster's utility. In addition, to explore whether the caregiver exposure to the poster could already have some effect on patient dysphagia-related health, patient risk of aspiration, food swallowing capacity, nutritional status, and oral cavity health were assessed before and one month after placement of the poster, and the poster-exposed group was compared with a (randomly-assigned) non-exposed group (n = 21). Data were analyzed with descriptive statistics and generalized linear models based on analyses of covariance. All caregivers across various education levels reported noticing, reading, and understanding the poster (100%). Nearly all reported that the poster added new information to their knowledge (17 out of 21). In the additional analysis, the patients in the poster-exposed group showed greater improvements in the health outcomes, compared with the non-exposed group, although the effects were statistically non-significant within this study's one-month period. A poster with pictorial information was effective in increasing awareness about dysphagia-specific information among caregivers of patients in inpatient care and can be used as an augmentative means of information, with potential benefits for patient safety and rehabilitation.

Simultaneous monitoring of amoxicillin and paracetamol in synthetic biological fluids using a 3D printed disposable electrode with a lab-made conductive filament.

In this work, we are pleased to present for the first time a 3D-printed electrochemical device using a lab-made conductive filament based on graphite (Gr) and polylactic acid (PLA) polymer matrix for the simultaneous detection of amoxicillin (AMX) and paracetamol (PAR). The sensor was properly characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). Compared to the commercial glassy carbon electrode (GCE), the superior performance of the 3D-Gr/PLA electrode was verified with a 3.8-fold more favored charge transfer. A differential pulse voltammetry (DPV) method was proposed providing a linear working range of 4 to 12 µmol L-1 for both analytes and a limit of detection (LOD) of 0.80 and 0.51 µmol L-1 for AMX and PAR, respectively. Additionally, repeatability studies (n = 5, RSD < 5.7%) indicated excellent precision, and recovery percentages ranging from 89 to 109% when applied to synthetic human urine, saliva, and plasma samples, attested to the accuracy of the method. The studies also indicate that the sensor does not suffer significant interference from common substances (antibiotics and biomarkers) present in the biological fluids, which makes it a promising analytical tool considering its low-cost, ease of manufacturing, robustness, and electrochemical performance.

Rehabilitation Improves Persistent Symptoms of COVID-19: A Nonrandomized, Controlled, Open Study in Brazil.

OBJECTIVE: This study aimed to investigate the effects of an 8-wk face-to-face rehabilitation program on subjects with persistent symptoms of COVID-19 compared with a remote monitoring group. DESIGN: This is clinical, nonrandomized, controlled, and open study. The face-to-face supervised rehabilitation lasted eight consecutive weeks, twice a week. The remote monitoring group received health guidance. The allocation was carried out by preference because of the emergency period without vaccination during the pandemic. Fatigue, dyspnea (Pulmonary Functional Status and Dyspnea Questionnaire), and exercise capacity (Incremental Shuttle Walk Test) were the primary outcome measures. Lung function, functional status (Post-COVID-19 Functional Status), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale), attention (d2-R), memory (Rey's Auditory-Verbal Learning Test), handgrip strength, and knee extensor strength were secondary outcome measures. RESULTS: Thirty-seven subjects (24.3% hospitalized) completed the baseline and final assessment, rehabilitation ( n = 22, 40.8 [SD, 10.0] yrs, 54.5% female), or remote guidance ( n = 15, 45.4 [SD, 10.5] yrs, 40% female). Both groups showed improved fatigue and exercise capacity. Exercise rehabilitation improved dyspnea, anxiety, attention, and short-term memory. CONCLUSIONS: Rehabilitation is essential for dyspnea in subjects with persistent symptoms of COVID-19 while fatigue naturally reverses.

Communication and swallowing training of stroke-specialized health professionals using transdisciplinary knowledge in a patient-actor scenario: A case report.

BACKGROUND: Most people with stroke exhibit a variety of impairments that need to be addressed by a multidisciplinary team. Communication and swallowing disorders are common and should be screened very early. To guarantee a patient-centred approach, all patients, even those with speech and language disorders, must be actively engaged in the healthcare process. Effective communication is essential to success in many of the needed interventions. However, healthcare professionals often do not receive formal training in communicating with these patients, thus increasing the risk of preventable adverse events. AIMS: To describe the design, implementation and evaluation of a post-acute stroke multidisciplinary team training using patient actors in a simulation approach. METHODS & PROCEDURES: A 2-day course focused on the transdisciplinary knowledge related to communication and swallowing that all members of the multidisciplinary stroke team should acquire was implemented. A case-based learning methodology used simulation and resorting to patients' actors. Learning outcomes were evaluated by comparing the results obtained in two knowledge tests, one for each topic, which participants performed before and after each day course. Reaction to the training was gathered concerning the content, teacher quality and course organization. The follow-up was performed 6 months later to assess training skills transfer to the workplace environment. OUTCOMES & RESULTS: All the participants considered that the programme objectives were relevant or truly relevant and revealed that the programme's dynamic, rhythm and scenarios set were excellent. After the end of the programme, both communication and swallowing knowledge increased. Most participants had the opportunity to employ the acquired training skills in their work environment. The main barriers identified to implementing these skills were the 'need for additional training', the 'lack of time' or 'the lack of opportunities'. CONCLUSIONS & IMPLICATIONS: Simulation is a central method to increase and improve health professionals' skills when intervening with stroke patients. Using simulation with patient actors allows flexibility and diversification of clinical situations under analysis, which can provide a multiplier effect of reflection and learning. The implemented training achieved its objectives. WHAT THIS PAPER ADDS: What is already known on this subject Simulation in the training of health professionals is increasingly used as a good practice, allowing the recreation of scenarios identical to those in the context of professional practice. This strategy is used not only in initial training but also for the development of advanced skills. What this study adds to the existing knowledge This study reports the use of simulation using actor patients for the development of transdisciplinary skills in the topics of communication and swallowing in people with stroke What are the clinical and practical implications of this work? The study demonstrates that in a short period of training, the use of simulation with actor patients favours the development of transdisciplinary skills in the topics of communication and swallowing in people with stroke. At the same time, the skills developed are transferable to professional practice.

Study of the DNA damage and cell death in human peripheral blood mononuclear and HepG2/C3A cells exposed to the synthetic 3-(3-hydroxyphenyl)-7-hydroxycoumarin.

Hydroxycoumarins are an important source of biologically active compounds. Previous studies have shown that the number and position of the hydroxyl substituents in the scaffold play an important role for the observed biological activity. In the present study, 3-(3-hydroxyphenyl)-7-hydroxycoumarin was synthesized, and potential cytogenotoxic effects determined in human HepG2/C3A cells displaying phase 1 and phase 2 enzymes (metabolizing cell ability) and compared to human peripheral blood mononuclear cells (PBMC) without xenobiotics metabolizing capacity. Cell viability was determined with concentrations between 0.01 and 10 µg/ml of 3-(3-hydroxyphenyl)-7-hydroxycoumarin using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and trypan blue tests. Genotoxicity was determined utilizing the comet assay, and the clastogenic/aneugenic potential employing the micronucleus (MN) test. The results of the in vitro cytotoxicity assays showed a significant decrease in cell viability of PBMC following exposure to 10 µg/ml concentration of the studied compound after 48 and 72 hr. Comet assay observations noted significant DNA damage in PBMC after 4 hr treatment. No marked cytogenotoxic effects were found in HepG2/C3A cells. No chromosomal mutations were observed in both cell lines. It is important to note that 3-(3-hydroxyphenyl)-7-hydroxycoumarin may exert beneficial pharmacological actions at the low micromolar range and with half-life less than 24 hr. Therefore, the results obtained encourage the continuation of studies on this new molecule for medicinal purposes, but its potential toxicity at higher concentrations and longer exposure times needs to be investigated in further studies.

Simultaneous stoma closure and type IV parastomal hernia repair after botulinum toxin and progressive pneumoperitoneum.

Surgery is the only treatment for parastomal hernia (PH). When possible, stoma closure is the best way to manage this type of hernia, however, whether to perform it in a single approach with abdominal wall reconstruction (AWR) is still debatable. A 58-year-old woman with a type IV PH with loss of domain was submitted to preoperative optimization [botulinum toxin type A and progressive pneumoperitoneum (PPP)], followed by simultaneous stoma closure and AWR. Hospital discharge was on the eighth day with no complications. Six months later, no clinical evidence of recurrence or other complication was observed. Large PHs are technically challenging. Stoma closure and simultaneous AWR increase surgical risk. Preoperative optimization with a combination of adjuvants (including PPP) is feasible in PH and may overcome technical complexity, even though patient selection remains the key when choosing a PH repair with synchronous stoma closure.

Recommendations of good practice to prevent aspiration pneumonia in older adults at risk of oropharyngeal dysphagia living in nursing homes: A modified e-Delphi study protocol.

BACKGROUND: Aspiration pneumonia (AP) is a subset of pneumonia caused by the aspiration of food and fluids to the lungs and is highly prevalent in the older population. Oropharyngeal dysphagia (OD) is one of the risk factors for AP and it is also associated with malnutrition, dehydration and poor functional outcomes. As pneumonia is the second most common infection in nursing homes (NHs) and OD represents a major concern to NH staff, good practices for the prevention of AP in older adults at risk of OD are needed. PURPOSE: The aim of this modified e-Delphi study is to build consensus among a panel of experts regarding a set of recommendations for NH staff on good practices to prevent AP in older adults at risk of OD living in NHs. The objective of this paper is to establish the methodology inherent to the Delphi study. METHODS: An online modified Delphi study will be developed in three rounds. Criteria for the Delphi panel participants include holding a master's or doctoral degree in OD or speech and language therapy; or having 10 or more years of experience in OD; or having at least one scientific publication related to OD. A previously described modified Delphi methodology will be used to achieve consensus (75% agreement). An additional round will be performed to collect the experts' perspectives regarding the priority for application of each recommendation previously validated. DISCUSSION: This protocol aimed to describe the methodology of a future Delphi study on the prevention of AP, seeking to fulfil the gap in the literature regarding this topic. The modified Delphi technique is a widely used method for collecting experts' opinion in health sciences, but the absence of standardised guidelines allows some heterogeneity between studies with the same aim. WHAT THIS PAPER ADDS: What is already known on the subject Aspiration pneumonia (AP) is related to three main risk factors: impaired safety of swallow, impaired nutritional status and poor oral health. It is known that being dependent for feeding is one of the main risk factors for AP and around 50% of nursing home (NH) residents need feeding assistance. Thus, it is important to promote specialised intervention and care by the NH staff for preventing AP. What this paper adds to existing knowledge It is hypothesised that increasing the knowledge of NH staff regarding the best practices for preventing AP in older adults at risk of oropharyngeal dysphagia (OD) will improve outcomes such as quality of life, incidence of AP and mortality. What are the potential or actual clinical implications of this work? The recommendations resulting from this study will address a current gap in healthcare practice of NH staff regarding older adults at increased risk for OD and, consequently, for AP.

Effect of Lubricant Use on Cervicovaginal Cytology - What's the Evidence?

OBJECTIVE: To determine if the use of lubricating gel on the speculum during the cervicovaginal cytology examination interferes with the results obtained, as well as whether it reduces reported discomfort in patients. DATA SOURCES: A systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, with a search in the Pubmed/Medline, Scielo, Cochrane Library, Embase databases of articles published between January 2011 and May 2022. The keywords used were cytology, speculum, lubricant, result, and pain. SELECTION OF STUDIES: The initial search resulted in 306 articles, of which were excluded three because they were duplicates, 257 after reading the title and abstract and 41 after reading the full text. Thus, five articles were selected for the study: four randomized clinical trials and one metanalysis. DATA COLLECTION: The selection of articles was performed by two investigators. The 5 selected articles were read in full and submitted to a comparative analysis. DATA SYNTHESIS: Screening through cervicovaginal cytology allows for early diagnosis and reduction of associated mortality, but the procedure can be associated with pain. A small amount of aqueous lubricating gel in the speculum can be used to reduce the discomfort associated with performing cervicovaginal cytology. CONCLUSION: The use of lubricating gel in the speculum does not seem to be associated with a change in the cytology result and reduces the discomfort associated with its insertion into the vagina.

OBJETIVO: Determinar se o uso de gel lubrificante no espéculo durante o exame de citologia cervicovaginal interfere com os resultados obtidos e se diminui o desconforto relatado por pacientes. FONTES DE DADOS: Foi realizada uma revisão sistemática segundo as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com pesquisa nas bases de dados Pubmed/Medline, Scielo, Cochrane Library, Embase, de artigos publicados entre janeiro de 2011 e julho de 2022. Utilizaram-se as palavras-chave citologia, espéculo, lubrificante, resultado e dor. SELEçãO DOS ESTUDOS: A pesquisa inicial resultou em 306 artigos, dos quais foram excluídos três por se encontrarem duplicados, 257 após a leitura do título e do resumo e 41 após a leitura integral. Assim, foram selecionados cinco artigos para o estudo: quatro ensaios clínicos aleatorizados e uma metanálise. COLETA DE DADOS: A seleção dos artigos foi realizada por dois investigadores. Os cinco artigos selecionados foram lidos na íntegra e submetidos a uma análise comparativa. SíNTESE DOS DADOS: O rastreio através da citologia cervicovaginal permite um diagnóstico precoce e redução da mortalidade associada, mas a sua realização pode estar associada a dor. Uma pequena quantidade de gel lubrificante aquoso pode ser utilizada no espéculo para diminuir o desconforto associado à realização da citologia cervicovaginal. CONCLUSãO: A utilização de gel lubrificante não está associada a alteração do resultado da citologia e diminui o desconforto associado à sua introdução na vagina.

Design of 3-Phenylcoumarins and 3-Thienylcoumarins as Potent Xanthine Oxidase Inhibitors: Synthesis, Biological Evaluation, and Docking Studies.

Coumarin scaffold has proven to be promising in the development of bioactive agents, such as xanthine oxidase (XO) inhibitors. Novel hydroxylated 3-arylcoumarins were designed, synthesized, and evaluated for their XO inhibition and antioxidant properties. 3-(3'-Bromophenyl)-5,7-dihydroxycoumarin (compound 11) proved to be the most potent XO inhibitor, with an IC50 of 91 nM, being 162 times better than allopurinol, one of the reference controls. Kinetic analysis of compound 11 and compound 5 [3-(4'-bromothien-2'-yl)-5,7-dihydroxycoumarin], the second-best compound within the series (IC50 of 280 nM), has been performed, and both compounds showed a mixed-type inhibition. Both compounds present good antioxidant activity (ability to scavenge ABTS radical) and are able to reduce reactive oxygen species (ROS) levels in H2 O2 -treated cells. In addition, they proved to be non-cytotoxic in a Caco-2 cells viability assay. Molecular docking studies have been carried out to correlate the compounds' theoretical and experimental binding affinity to the XO binding pocket.

A comprehensive LC-UHPLC-MS/MS method for the monitoring of N-nitrosamines in lipophilic drugs: A case study with rifampicin.

In the last five years, the presence of N-nitrosamines in commonly used medicines has become a significant concern for patients, physicians, and the pharmaceutical industry, due to their carcinogenic properties, even at low concentrations. Analytical methods that enable the unequivocal monitoring of these compounds, with low detection limits and covering a range of drugs, are indispensable. The present work proposes a bidimensional liquid chromatography-tandem mass spectrometry method capable of quantifying eleven N-nitrosamines in lipophilic active pharmaceutical ingredients (APIs). The API is retained in the first chromatographic dimension, while the fraction containing the N-nitrosamines is transferred to the second chromatographic dimension and, after separation, to the mass spectrometer. The logP values for the APIs and N-nitrosamines enabled prediction of the APIs that could be separated from the target analytes. The method was validated and successfully applied for the quantification of 1-methyl-4-nitroso piperazine (MNP) and N-nitrosodimethylamine (NDMA) in rifampicin, a drug used to treat tuberculosis. Although NDMA was not detected in two pharmaceutical analyzed, MNP was found at concentrations of 0.44 ± 0.05 and 2.1 ± 0.3 µg g-1. Given the ability to apply the method to various APIs, together with its reliance solely on logP values for determining suitability, the proposed technique could be extended to the determination of N-nitrosamines in other drugs besides rifampicin.

Elevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS.

Background Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95% CI, 1.0-1.9]; P=0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95% CI, 1.0-1.3]; P=0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95% CI, 1.1-2.7]; P=0.01). Conclusions Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.

Cost-effective protocol to produce 3D-printed electrochemical devices using a 3D pen and lab-made filaments to ciprofloxacin sensing.

A novel conductive filament based on graphite (Gr) dispersed in polylactic acid polymer matrix (PLA) is described to produce 3D-electrochemical devices (Gr/PLA). This conductive filament was used to additively manufacture electrochemical sensors using the 3D pen. Thermogravimetric analysis confirmed that Gr was successfully incorporated into PLA, achieving a composite material (40:60% w/w, Gr and PLA, respectively), while Raman and scanning electron microscopy revealed the presence of defects and a high porosity on the electrode surface, which contributes to improved electrochemical performance. The 3D-printed Gr/PLA electrode provided a more favorable charge transfer (335 Ω) than the conventional glassy carbon (1277 Ω) and 3D-printed Proto-pasta® (3750 Ω) electrodes. As a proof of concept, the ciprofloxacin antibiotic, a species of multiple interest, was selected as a model molecule. Thus, a square wave voltammetry (SWV) method was proposed in the potential range + 0.9 to + 1.3 V (vs Ag|AgCl|KCl(sat)), which provided a wide linear working range (2 to 32 µmol L-1), 1.79 µmol L-1 limit of detection (LOD), suitable precision (RSD < 7.9%), and recovery values from 94 to 109% when applied to pharmaceutical and milk samples. Additionally, the sensor is free from the interference of other antibiotics routinely employed in veterinary practices. This device is disposable, cost-effective, feasibly produced in financially limited laboratories, and consequently promising for evaluation of other antibiotic species in routine applications.

Quality Standard for Rehabilitation of Young Deaf Children Receiving Cochlear Implants.

Background and objectives: More and more children with severe-to-profound hearing loss are receiving cochlear implants (CIs) at an early age to improve their hearing and listening abilities, speech recognition, speech intelligibility, and other aspects of spoken language development. Despite this, the rehabilitation outcomes can be very heterogeneous in this population, not only because of issues related to surgery and fitting or the specific characteristics of the child with his/her additional disabilities but also because of huge differences in the quality of the support and rehabilitation offered by the therapist and the family. These quality standards for the rehabilitation of young deaf children receiving CIs are developed within the European KA202 Erasmus+ project "VOICE"-vocational education and training for speech and language therapists and parents for the rehabilitation of children with CIs, Ref. No.: 2020-1-RO01-KA202-080059. Material and methods: To develop these quality standards, we used the input from the face-to-face interviews of 11 local rehabilitation experts in CIs from the four partner countries of the project and the outcomes of the bibliographic analysis of 848 publications retrieved from six databases: Pub Med, Psych Info, CINAHL, Scopus, Eric, and Cochrane. Based on all this information, we created a first set of 32 quality standards over four domains: general, fitting, rehabilitation, and for professionals. Further on, the Delphi method was used by 18 international rehabilitation experts to discuss and agree on these standards. Results: The results from the literature analysis and the interviews show us that more than 90% of the consulted international experts agreed on 29 quality standards. They focus on different aspects of rehabilitation: the multidisciplinary team, their expertise and knowledge, important rehabilitation topics to focus on, and programming issues related to rehabilitation. Conclusions: These quality standards aim to optimize the activity of speech rehabilitation specialists so that they reach the optimal level of expertise. Also presented is the necessary equipment for the IC team to carry out the rehabilitation sessions in good conditions. This set of quality standards can be useful to ensure the appropriate postoperative care of these children. As a result, the rehabilitation process will be more relaxed, and therapists will have the opportunity to focus more on the specific needs of each child, with the provision of quality services, which will result in better results. This theme is particularly complex and dependent on multifactorial aspects of medicine, education, speech therapy, social work, and psychology that are very intricate and interdependent.