Monitoring of a microbial community during bioaugmentation with hydrogenotrophic methanogens to improve methane yield of an anaerobic digestion process.

Methane production by microbial fermentation of municipal waste is a challenge for better yield processes. This work describes the characterization of a hydrogenotrophic methanogen microbial community used in a bioaugmentation procedure to improve the methane yield in a thermophilic anaerobic process, digesting the organic fraction of municipal solid waste. The performance of the bioaugmentation was assessed in terms of methane production and changes in the microbial community structure. The results showed that bioaugmentation slightly improved the cumulative methane yield (+ 4%) in comparison to the control, and its use led to an acceleration of the methanogenesis stage. We observed associated significant changes in the relative abundance of taxa and their interactions, using high throughput DNA sequencing of V3-16S rRNA gene libraries, where the abundance of the archaeal hydrogenotrophic genus Methanoculleus (class Methanomicrobia, phylum Euryarchaeota) and the bacterial order MBA08 (class Clostridia, phylum Firmicutes) were dominant. The relevant predicted metabolic pathways agreed with substrate degradation and the anaerobic methanogenic process. The purpose of the study was to evaluate the effect of the addition of hydrogenotrophic methanogens in the generation of methane, while treating organic waste through anaerobic digestion.

Infectious disease evaluations in a psychiatric unit, an observational study.

Patients in adult psychiatric wards present infectious complications or pathologies that mimic an infectious condition, and there is little information on this subject. OBJECTIVES: To know the frequency and infectious and non-infectious complications treated by infectious disease specialists in a psychiatric intensive-care hospitalization unit for adults and their outcomes. METHODS: Observational study between 2016 and 2021. RESULTS: 37 patients with 41 events were evaluated. Almost half of the visits to these events originated from an antimicrobial stewardship program (46.3%). In 68.3% of the events, complementary studies were requested; in 14.6%, referral to other specialties; in 26.8%, an antimicrobial treatment was started; and in 75%, modifications were made to previous schemes. An infectious cause was identified in 30 of 41 events (73.2%) that included the following conditions: respiratory (31.7%), skin (9.8%), urinary (7.3%), gynecological (2.4%), one case of bacteremia with unknown source (2.4%), sequential infections (4.9%) and HIV therapy dropouts (7.3%). In the 11 remaining events, non-infectious causes were identified (26.8%): pulmonary thromboembolism, drug hepatotoxicity, false positive VDRL and HIV tests, steroid-induced psychosis in an HIV patient with thrombocytopenia, fever without etiology, residual positive SARS-CoV-2 PCR test, low O2 pulse oximetry due to oversedation and neuroleptic malignant syndrome. There was no mortality. CONCLUSIONS: Patients in psychiatric hospitalization wards suffer from a great diversity of infectious problems during their stay with conditions that simulate infections. An antibiotic surveillance system can detect half of these conditions. The infectious diseases visits allow for advising or reorienting of the study and modifying the antibiotic treatment.

Gastroparesis associated to isoniazid. First description.

Isoniazid, a central compound in the treatment of active or latent tuberculosis, is associated with various adverse reactions, including hepatitis and polyneuropathy. The latter is due to functional pyridoxine depletion and can be avoided by appropriate doses and supplementation with pyridoxine. We present the case of a patient with several previous treatment abandonments for active pulmonary tuberculosis who evolved with late postprandial vomiting due to gastroparesis documented by nuclear medicine gastric emptying tests after a new treatment onset. Gastroparesis improved with discontinuation of isoniazid and levosulpiride, reappeared with re-exposure, and improved with definitive withdrawal of isoniazid. Morbidity associated with vomiting led to prolonged hospitalization and treatment failure without the emergence of antituberculosis drug resistance. The association of gastroparesis with isoniazid was considered definitive when applying at least two causality protocols. Gastroparesis associated with isoniazid should be added to the list of adverse effects associated with this drug, even in patients receiving pyridoxine supplementation. Its recognition is initially clinical, can be confirmed with nuclear medicine studies, and affects the eradication of Mycobacterium tuberculosis.

Achieving Absolute Molar Lipid Concentrations: A Phospholipidomics Cross-Validation Study.

Standardization is essential in lipidomics and part of a huge community effort. However, with the still ongoing lack of reference materials, benchmarking quantification is hampered. Here, we propose traceable lipid class quantification as an important layer for the validation of quantitative lipidomics workflows. 31P nuclear magnetic resonance (NMR) and inductively coupled plasma (ICP)-mass spectrometry (MS) can use certified species-unspecific standards to validate shotgun or liquid chromatography (LC)-MS-based lipidomics approaches. We further introduce a novel lipid class quantification strategy based on lipid class separation and mass spectrometry using an all ion fragmentation (AIF) approach. Class-specific fragments, measured over a mass range typical for the lipid classes, are integrated to assess the lipid class concentration. The concept proved particularly interesting as low absolute limits of detection in the fmol range were achieved and LC-MS platforms are widely used in the field of lipidomics, while the accessibility of NMR and ICP-MS is limited. Using completely independent calibration strategies, the introduced validation scheme comprised the quantitative assessment of the complete phospholipid sub-ome, next to the individual lipid classes. Komagataella phaffii served as a prime example, showcasing mass balances and supporting the value of benchmarks for quantification at the lipid species level.

Development of a guideline for the treatment of generalized anxiety disorder with the ADAPTE method.

OBJECTIVE: The aim was to develop a clinical guideline for managing generalised anxiety disorder in Primary Health Care and Mental Health, using guideline adaptation methods. DESIGN: A clinical guideline was developed, following the methods of the ADAPTE group, and implemented in a Primary Health Care District and in Mental Health Services in Spain. SETTING: Regional University Hospital of Málaga and District of Primary Health Care Málaga-Guadalhorce (Spain). PARTICIPANTS: The participants were family physicians, psychiatrists and clinical psychologists. The phases of the process included definition of clinical scenarios, literature search and guidelines appraisal, elaboration of recommendations, conducting focus groups with users diagnosed with generalised anxiety disorder, linking the testimonials of users with recommendations, external review and implementation by multifaceted interventions. RESULTS: The final release included 49 Recommendations, of which 47 are from the 2011 NICE guidance for GAD and 2 of the 2011 NICE guideline for common mental disorder. Finally, seven recommendations needed to be adapted to the Spanish health care context, and three recommendations were excluded. CONCLUSIONS: A guideline aimed to improve the quality and effectiveness of the care provided to people with generalised anxiety disorder has been released. The use of adaptation methods has simplified the use of resources and time. This guideline and the process designed for its implementation constitute a suitable collection of resources for the improvement on detection and treatment of GAD in primary health care. Adaptation methods play a key role in the knowledge translation continuum.

Critical assessment of different methods for quantitative measurement of metallodrug-protein associations.

Quantitative screening for potential drug-protein binding is an essential step in developing novel metal-based anticancer drugs. ICP-MS approaches are at the core of this task; however, many applications lack in the capability of large-scale high-throughput screenings and proper validation. In this work, we critically discuss the analytical figures of merit and the potential method-based quantitative differences applying four different ICP-MS strategies to ex vivo drug-serum incubations. Two candidate drugs, more specifically, two Pt(IV) complexes with known differences of binding affinity towards serum proteins were selected. The study integrated centrifugal ultrafiltration followed by flow injection analysis, turbulent flow chromatography (TFC), and size exclusion chromatography (SEC), all combined with inductively coupled plasma-mass spectrometry (ICP-MS). As a novelty, for the first time, UHPLC SEC-ICP-MS was implemented to enable rapid protein separation to be performed within a few minutes at > 90% column recovery for protein adducts and small molecules. Graphical abstract Quantitative screening for potential drug-protein binding is an essential step in developingnovel metal-based anticancer drugs.

Transgenic papaya: a useful platform for oral vaccines.

MAIN CONCLUSION: Transgenic papaya callus lines expressing the components of the S3Pvac vaccine constitute a stable platform to produce an oral vaccine against cysticercosis caused by Taenia solium or T. crassiceps. The development of effective delivery systems to cope with the reduced immunogenicity of new subunit vaccines is a priority in vaccinology. Herein, experimental evidence supporting a papaya-based platform to produce needle-free, recombinant, highly immunogenic vaccines is shown. Papaya (Carica papaya) callus lines were previously engineered by particle bombardment to express the three protective peptides of the S3Pvac anti-cysticercosis vaccine (KETc7, KETc12, KETc1). Calli were propagated in vitro, and a stable integration and expression of the target genes has been maintained, as confirmed by PCR, qRT-PCR, and HPLC. These results point papaya calli as a suitable platform for long-term transgenic expression of the vaccine peptides. The previously demonstrated protective immunogenic efficacy of S3Pvac-papaya orally administered to mice is herein confirmed in a wider dose-range and formulated with different delivery vehicles, adequate for oral vaccination. This protection is accompanied by an increase in anti-S3Pvac antibody titers and a delayed hypersensitivity response against the vaccine. A significant increase in CD4+ and CD8+ lymphocyte proliferation was induced in vitro by each vaccine peptide in mice immunized with the lowest dose of S3Pvac papaya (0.56 ng of the three peptides in 0.1 µg of papaya callus total protein per mouse). In pigs, the obliged intermediate host for Taenia solium, S3Pvac papaya was also immunogenic when orally administered in a two-log dose range. Vaccinated pigs significantly increased anti-vaccine antibodies and mononuclear cell proliferation. Overall, the oral immunogenicity of this stable S3Pvac-papaya vaccine in mice and pigs, not requiring additional adjuvants, supports the interest in papaya callus as a useful platform for plant-based vaccines.

Effects of prone positioning on lung protection in patients with acute respiratory distress syndrome.

RATIONALE: Positive end-expiratory pressure (PEEP) and prone positioning may induce lung recruitment and affect alveolar dynamics in acute respiratory distress syndrome (ARDS). Whether there is interdependence between the effects of PEEP and prone positioning on these variables is unknown. OBJECTIVES: To determine the effects of high PEEP and prone positioning on lung recruitment, cyclic recruitment/derecruitment, and tidal hyperinflation and how these effects are influenced by lung recruitability. METHODS: Mechanically ventilated patients (Vt 6 ml/kg ideal body weight) underwent whole-lung computed tomography (CT) during breath-holding sessions at airway pressures of 5, 15, and 45 cm H2O and Cine-CTs on a fixed thoracic transverse slice at PEEP 5 and 15 cm H2O. CT images were repeated in supine and prone positioning. A recruitment maneuver at 45 cm H2O was performed before each PEEP change. Lung recruitability was defined as the difference in percentage of nonaerated tissue between 5 and 45 cm H2O. Cyclic recruitment/de-recruitment and tidal hyperinflation were determined as tidal changes in percentage of nonaerated and hyperinflated tissue, respectively. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients with ARDS were included. Increasing PEEP from 5 to 15 cm H2O decreased nonaerated tissue (501 ± 201 to 322 ± 132 grams; P < 0.001) and increased tidal-hyperinflation (0.41 ± 0.26 to 0.57 ± 0.30%; P = 0.004) in supine. Prone positioning further decreased nonaerated tissue (322 ± 132 to 290 ± 141 grams; P = 0.028) and reduced tidal hyperinflation observed at PEEP 15 in supine patients (0.57 ± 0.30 to 0.41 ± 0.22%). Cyclic recruitment/de-recruitment only decreased when high PEEP and prone positioning were applied together (4.1 ± 1.9 to 2.9 ± 0.9%; P = 0.003), particularly in patients with high lung recruitability. CONCLUSIONS: Prone positioning enhances lung recruitment and decreases alveolar instability and hyperinflation observed at high PEEP in patients with ARDS.

Probabilistic material flow analysis of released nano titanium dioxide in Mexico.

Engineered Nanomaterials (ENMs) or products containing ENMs, known as nano-enabled products are commercialized globally by a large number of companies. Concern about the potential risks and negative impacts of releasing ENMs into the environment is under investigation. For this reason, methodologies to estimate the probable mass concentrations of ENMs released in different regions of the world have been developed. As a first attempt to estimate the probable mass flows of nanosized titanium dioxide (nano-TiO2) released in Mexico, we developed a Probabilistic Material Flow Analysis (PMFA) for 2015. The model describes probabilistic mass flows of released nano-TiO2 during the life cycle of sunscreens, coatings, ceramic, and other nano-enabled products, including the flows through the solid waste and wastewater management systems, as well as the transfer of nano-TiO2 to three environmental compartments (atmosphere, topsoil, and surface water). The PMFA incorporates the uncertainty related to the input data. We observed that the most significant nano-TiO2 flows occur to the surface water, landfill, and soil compartments, targeted as the main "hot-spots", where living organisms could be more exposed to this material. Further improvements in the model are needed due to some data gaps at some life cycle stages, for instance, solid waste management and reused wastewater manipulation for irrigation purposes. Finally, the model developed in this study can be adjusted to assess other ENM releases and can be beneficial for further investigation in fate modeling and environmental risk assessment.

Albumin-targeting of an oxaliplatin-releasing platinum(iv) prodrug results in pronounced anticancer activity due to endocytotic drug uptake in vivo.

Oxaliplatin is a very potent platinum(ii) drug which is frequently used in poly-chemotherapy schemes against advanced colorectal cancer. However, its benefit is limited by severe adverse effects as well as resistance development. Based on their higher tolerability, platinum(iv) prodrugs came into focus of interest. However, comparable to their platinum(ii) counterparts they lack tumor specificity and are frequently prematurely activated in the blood circulation. With the aim to exploit the enhanced albumin consumption and accumulation in the malignant tissue, we have recently developed a new albumin-targeted prodrug, which supposed to release oxaliplatin in a highly tumor-specific manner. In more detail, we designed a platinum(iv) complex containing two maleimide moieties in the axial position (KP2156), which allows selective binding to the cysteine 34. In the present study, diverse cell biological and analytical tools such as laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS), isotope labeling, and nano-scale secondary ion mass spectrometry (NanoSIMS) were employed to better understand the in vivo distribution and activation process of KP2156 (in comparison to free oxaliplatin and a non-albumin-binding succinimide analogue). KP2156 forms very stable albumin adducts in the bloodstream resulting in a superior pharmacological profile, such as distinctly prolonged terminal excretion half-life and enhanced effective platinum dose (measured by ICP-MS). The albumin-bound drug is accumulating in the malignant tissue, where it enters the cancer cells via clathrin- and caveolin-dependent endocytosis, and is activated by reduction to release oxaliplatin. This results in profound, long-lasting anticancer activity of KP2156 against CT26 colon cancer tumors in vivo based on cell cycle arrest and apoptotic cell death. Summarizing, albumin-binding of platinum(iv) complexes potently enhances the efficacy of oxaliplatin therapy and should be further developed towards clinical phase I trials.

Efficient production of fatty acid methyl esters by a wastewater-isolated microalgae-yeast co-culture.

Improving the competitiveness of biodiesel production by microalgae cultures requires the application of several strategies to obtain a high content of lipids, rapid biomass growth and a capacity to adapt to different kinds of environment, with the aim of using non-renewable nutrient sources. Therefore, the use of an individual indigenous microalgae strain or a consortium from natural or anthropogenic sites is now considered an alternative for biofuel production. This study examined the temporal behaviour of secondary metabolites produced by a native microalgae and yeast consortium isolated from wastewater, which was characterized by a genetic identification method based on the MiSeq system. The predominant species in the consortium was Scenedesmus obliquus, representing 68% of the organisms. In addition, the consortium contained a number of yeast species, including Candida pimensis (43%), Arthroderma vanbreuseghemii (23%), Diaporthe aspalathi/Diaporthe meridionalis (25%) and Hericium americanum (3%). This indigenous co-culture of microalgae and yeast showed biomass productivity of 0.06 g l-1 day-1, with a content of 30% (w/w) carbohydrates, 4% (w/w) proteins and 55% (w/w) lipids. Transesterification of the extracted lipids produced fatty acid methyl esters (FAMEs), which were analysed by gas chromatography (GC). The FAMEs included methyl pentadecanoate (1.90%), cis-10-pentanedecanoic acid methyl ester (1.36%), methyl palmitate (2.64%), methyl palmitoleate (21.36%), methyl oleate (64.95%), methyl linolenate (3.83%) and methyl linolelaidate (3.95%). This composition was relevant for biodiesel production based on the co-culture of indigenous microalgae and yeast consortia.

[Concentration of titanium in respiratory tissue obtained from autopsies in Mexico city residents]. / Concentración de titanio en tejido respiratorio obtenido de autopsias en residentes de la ciudad de México.

OBJETIVOS.: To quantify the levels of titanium (Ti) in respiratory tissue obtained by autopsy in people who resided in Mexico City. MATERIALS AND METHODS.: An exploratory study was conducted in which 216 samples of respiratory tissue from pulmonary lobes and peribronchial lymph nodes were obtained from legal medical autopsies of 36 corpses with a minimum of two years of residence in Mexico City. Histopathological analyses of the samples were performed and the Ti existing in them was quantified by induction plasma coupled to atomic absorption spectrophotometry. RESULTS.: The amount of Ti in respiratory tissue was distributed between 0 micrograms of Ti in dry tissue (µg Ti/g ts) and 39.7 µg Ti/g ts; the presence of Ti was identified as distributed in up to six times a higher quantity in the lymph nodes than in pulmonary lobes. Cluster analysis showed that the sample consisted of four groups of individuals grouped according to the amount and distribution of Ti in the lower respiratory tract, age, body mass index, place and time of residence in Mexico City. CONCLUSIONS: . Due to the distribution pattern observed, Ti found in respiratory tissue samples may come from urban air; the amount of Ti in conjunction with other elements may be the cause of respiratory pathologies.

OBJETIVOS.: Cuantificar la cantidad de titanio (Ti) en tejido respiratorio obtenidas por autopsia en personas que residieron en la Ciudad de México. MATERIALES Y MÉTODOS.: Se realizó un estudio exploratorio en el cual se obtuvieron 216 muestras de tejido respiratorio de lóbulos pulmonares y nódulos linfáticos peribronquiales, procedentes de autopsias médico legales de 36 cadáveres con antecedente de haber residido un mínimo de dos años en la Ciudad de México. Se realizaron análisis histopatológicos de las muestras y se cuantificó el Ti existente en ellas mediante plasma de inducción acoplado a la espectrofotometría de absorción atómica. RESULTADOS.: La cantidad de Ti en tejido respiratorio se distribuyó entre 0 microgramos de Ti en tejido seco (µg Ti/g ts) y 39,7 µg Ti/g ts, se identificó la presencia de Ti distribuido hasta en seis veces mayor cantidad en los nódulos linfáticos que en lóbulos pulmonares. El análisis de conglomerados mostró que la muestra estaba conformada por cuatro grupos de individuos agrupados de acuerdo a la cantidad y distribución del Ti en el tracto respiratorio bajo, a la edad, índice de masa corporal, lugar y tiempo de residencia en la ciudad de México. CONCLUSIONES.: Debido al patrón de distribución observado el Ti encontrado en las muestras de tejido respiratorio podría provenir del aire urbano, la cantidad de Ti en conjunto con otros elementos podría ser causante de patologías respiratorias.

Preclinical studies on metal based anticancer drugs as enabled by integrated metallomics and metabolomics.

Resistance development is a major obstacle for platinum-based chemotherapy, with the anticancer drug oxaliplatin being no exception. Acquired resistance is often associated with altered drug accumulation. In this work we introduce a novel -omics workflow enabling the parallel study of platinum drug uptake and its distribution between nucleus/protein and small molecule fraction along with metabolic changes after different treatment time points. This integrated metallomics/metabolomics approach is facilitated by a tailored sample preparation workflow suitable for preclinical studies on adherent cancer cell models. Inductively coupled plasma mass spectrometry monitors the platinum drug, while the metabolomics tool-set is provided by hydrophilic interaction liquid chromatography combined with high-resolution Orbitrap mass spectrometry. The implemented method covers biochemical key pathways of cancer cell metabolism as shown by a panel of >130 metabolite standards. Furthermore, the addition of yeast-based 13C-enriched internal standards upon extraction enabled a novel targeted/untargeted analysis strategy. In this study we used our method to compare an oxaliplatin sensitive human colon cancer cell line (HCT116) and its corresponding resistant model. In the acquired oxaliplatin resistant cells distinct differences in oxaliplatin accumulation correlated with differences in metabolomic rearrangements. Using this multi-omics approach for platinum-treated samples facilitates the generation of novel hypotheses regarding the susceptibility and resistance towards oxaliplatin.

[Aluminium in the lower respiratory tract of people living in México City]. / Aluminio en el Tracto Respiratorio Bajo de Residentes de la Ciudad de México.

OBJECTIVE: Investigating the presence of aluminium (Al) and respiratory pathologies in the lower respiratory tract of people who had lived in Mexico City for a minimum of two years. METHODS: 250 respiratory tissue samples were obtained from pulmonary lobes, lymph nodes, bronchial and hilum regions during 36 individuals' autopsies. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used for quantifying Al; the samples has been previously dried, ground and digested. RESULTS: 13 different pathologies were identified but only three of them (pulmonary emphysema, bronchitis and anthracosis) were correlated with the presence of Al, an element being distributed in very variable concentrations (range: 2.7 to 836.1 micrograms of Al per gram of dry tissue (ì g Al/g ts)). The amount of Al found in lobes, bronchial and hilum regions was much smaller than that found in lymph nodes; such difference was statistically significant. Multivariate analysis by conglomerates revealed that the sample consisted of three classes of individuals, grouped according to the amount and distribution of Al in the lower respiratory tract, age, time spent living in Mexico City and the presence of pathologies. CONCLUSIONS: The Al found in the lower respiratory tract of residents of Mexico City would thus seem to have come from the air. The amount of Al and its distribution pattern depended on the time and place of residence and can lead to respiratory illness.

Infectious disease evaluations in a psychiatric unit, an observational study / Visitas infectológicas a una unidad psiquiátrica, un estudio observacional

Patients in adult psychiatric wards present infectious complications or pathologies that mimic an infectious condition, and there is little information on this subject. OBJECTIVES: To know the frequency and infectious and non-infectious complications treated by infectious disease specialists in a psychiatric intensive-care hospitalization unit for adults and their outcomes. METHODS: Observational study between 2016 and 2021. RESULTS: 37 patients with 41 events were evaluated. Almost half of the visits to these events originated from an antimicrobial stewardship program (46.3%). In 68.3% of the events, complementary studies were requested; in 14.6%, referral to other specialties; in 26.8%, an antimicrobial treatment was started; and in 75%, modifications were made to previous schemes. An infectious cause was identified in 30 of 41 events (73.2%) that included the following conditions: respiratory (31.7%), skin (9.8%), urinary (7.3%), gynecological (2.4%), one case of bacteremia with unknown source (2.4%), sequential infections (4.9%) and HIV therapy dropouts (7.3%). In the 11 remaining events, non-infectious causes were identified (26.8%): pulmonary thromboembolism, drug hepatotoxicity, false positive VDRL and HIV tests, steroid-induced psychosis in an HIV patient with thrombocytopenia, fever without etiology, residual positive SARS-CoV-2 PCR test, low O2 pulse oximetry due to oversedation and neuroleptic malignant syndrome. There was no mortality. CONCLUSIONS: Patients in psychiatric hospitalization wards suffer from a great diversity of infectious problems during their stay with conditions that simulate infections. An antibiotic surveillance system can detect half of these conditions. The infectious diseases visits allow for advising or reorienting of the study and modifying the antibiotic treatment.

Los pacientes en salas de hospitalización psiquiátricas de adultos presentan complicaciones infecciosas o patologías que simulan un cuadro infeccioso y existe escasa información sobre este tema. OBJETIVOS: Conocer la frecuencia y tipo de complicaciones infecciosas y no infecciosas atendidas por especialistas de infectología en un Servicio de hospitalización psiquiátrica de cuidados intensivos de adultos y sus desenlaces. MÉTODOS: Estudio observacional entre el 2016 y 2021. RESULTADOS: Se visitaron 37 paciente con 41 eventos. Casi la mitad de las visitas en estos eventos se originó por seguimiento de antimicrobianos (46,3%). En el 68,3% de los eventos se solicitaron estudios complementarios, en 14,6% la opinión de otras especialidades, en 26,8% se inició un tratamiento antimicrobiano y en 75% se hicieron modificaciones a esquemas previos. En 30 de 41 eventos se identificó una causa infecciosa (73,2%) que incluyeron las siguientes condiciones: respiratorias (31,7%), cutáneas (9,8%), urinarias (7,3%), ginecológicas (2,4%), bacteremia sin foco (2,4%), infecciones secuenciales (4,9%) y abandonos de terapia en pacientes VIH (7,3%). En los 11 eventos restantes se identificaron causas no infecciosas (26,8%): tromboembolismo pulmonar, hepatotoxicidad por drogas, test VDRL y VIH falsos positivos, psicosis por esteroides en un paciente VIH con trombocitopenia, fiebre sin etiología, PCR SARS-CoV-2 positiva residual, desaturación de O2 por sedación y síndrome neuroléptico maligno. No hubo mortalidad en esta serie. CONCLUSIONES: Los pacientes en salas de hospitalización psiquiátrica sufren de una gran diversidad de problemas infecciosos durante su estadía junto a cuadros que simulan infecciones. Un sistema de vigilancia antibiótica permite detectar la mitad de estas condiciones. Las visitas infectológicas permiten asesorar o reorientar el estudio y modificar el tratamiento antibiótico.

The impact of whole human blood on the kinetic inertness of platinum(iv) prodrugs - an HPLC-ICP-MS study.

The potential advantage of platinum(iv) complexes as alternatives to classical platinum(ii)-based drugs relies on their kinetic stability in the body before reaching the tumor site and on their activation by reduction inside cancer cells. In this study, an analytical workflow has been developed to investigate the reductive biotransformation and kinetic inertness of platinum(iv) prodrugs comprising different ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of platinum(iv) complexes in blood pellets and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion. An analytical approach based on reversed-phase (RP)-ICP-MS was used to monitor the parent compound and the formation of metabolites using two different extraction procedures. The ligand coordination sphere of the platinum(iv) complexes had a significant impact on their accumulation in red blood cells and on their degree of kinetic inertness in whole human blood. The most lipophilic platinum(iv) compound featuring equatorial chlorido ligands showed a pronounced penetration into blood cells and a rapid reductive biotransformation. In contrast, the more hydrophilic platinum(iv) complexes with a carboplatin- and oxaliplatin-core exerted kinetic inertness on a pharmacologically relevant time scale with notable amounts of the compound accumulated in the plasma fraction.

An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity in vivo.

The design of targeted platinum(iv) prodrugs is a very promising approach to enhance the low selectivity of platinum(ii) drugs towards cancerous tissue in order to reduce the impact on healthy tissue and, consequently, the often severe side-effects. Herein, we report a set of mono-functionalized cis- and oxaliplatin-based platinum(iv) complexes bearing a maleimide moiety, which allows selective binding to serum albumin in the bloodstream. This leads not only to a prolonged plasma half-life by avoidance of fast renal clearance, but also to preferential accumulation of the drug in the tumor tissue due to the EPR-effect. Additionally, analogous succinimide-functionalized derivatives were prepared to verify the influence of the maleimide moiety. First experiments showed that all the maleimide compounds are stable and also possess good albumin-binding properties in whole serum. Further analytical studies on in vivo samples proved the highly increased plasma half-life, as well as tumor accumulation of the maleimide-functionalized substances. In vivo antitumor experiments with CT-26-bearing mice showed that, in contrast to the cisplatin derivatives, the oxaliplatin-based complexes had exceptionally better activity than the free drug resulting in the cure of the majority of treated mice. Subsequent analysis suggested that a distinctly faster reduction as well as reduced tumor accumulation of the cisplatin derivative might explain the worse performance compared to the oxaliplatin(iv) complexes. Taken together, a novel lead platinum(iv) complex with outstanding antitumor activity is presented, which will now be further developed towards clinical phase I trials.

Concentración de titanio en tejido respiratorio obtenido de autopsias en residentes de la ciudad de México / Concentration of titanium in respiratory tissue obtained from autopsies in Mexico city residents

RESUMEN Objetivos. Cuantificar la cantidad de titanio (Ti) en tejido respiratorio obtenidas por autopsia en personas que residieron en la Ciudad de México. Materiales y métodos. Se realizó un estudio exploratorio en el cual se obtuvieron 216 muestras de tejido respiratorio de lóbulos pulmonares y nódulos linfáticos peribronquiales, procedentes de autopsias médico legales de 36 cadáveres con antecedente de haber residido un mínimo de dos años en la Ciudad de México. Se realizaron análisis histopatológicos de las muestras y se cuantificó el Ti existente en ellas mediante plasma de inducción acoplado a la espectrofotometría de absorción atómica. Resultados. La cantidad de Ti en tejido respiratorio se distribuyó entre 0 microgramos de Ti en tejido seco (µg Ti/g ts) y 39,7 µg Ti/g ts, se identificó la presencia de Ti distribuido hasta en seis veces mayor cantidad en los nódulos linfáticos que en lóbulos pulmonares. El análisis de conglomerados mostró que la muestra estaba conformada por cuatro grupos de individuos agrupados de acuerdo a la cantidad y distribución del Ti en el tracto respiratorio bajo, a la edad, índice de masa corporal, lugar y tiempo de residencia en la ciudad de México. Conclusiones. Debido al patrón de distribución observado el Ti encontrado en las muestras de tejido respiratorio podría provenir del aire urbano, la cantidad de Ti en conjunto con otros elementos podría ser causante de patologías respiratorias.

ABSTRACT Objetivos. To quantify the levels of titanium (Ti) in respiratory tissue obtained by autopsy in people who resided in Mexico City. Materials and Methods. An exploratory study was conducted in which 216 samples of respiratory tissue from pulmonary lobes and peribronchial lymph nodes were obtained from legal medical autopsies of 36 corpses with a minimum of two years of residence in Mexico City. Histopathological analyses of the samples were performed and the Ti existing in them was quantified by induction plasma coupled to atomic absorption spectrophotometry. Results. The amount of Ti in respiratory tissue was distributed between 0 micrograms of Ti in dry tissue (µg Ti/g ts) and 39.7 µg Ti/g ts; the presence of Ti was identified as distributed in up to six times a higher quantity in the lymph nodes than in pulmonary lobes. Cluster analysis showed that the sample consisted of four groups of individuals grouped according to the amount and distribution of Ti in the lower respiratory tract, age, body mass index, place and time of residence in Mexico City. Conclusions . Due to the distribution pattern observed, Ti found in respiratory tissue samples may come from urban air; the amount of Ti in conjunction with other elements may be the cause of respiratory pathologies.

Reconstrucción dentoalveolar con implantes dentales mediante la técnica de levantamiento de seno maxilar / Dentoalveolar reconstruction with dental implants using the technique of maxillary sinus lifting

La colocación de implantes en el sector posterosuperior con frecuencia debe enfrentar casos de atrofia de reborde maxilar y neumatización del seno maxilar, para los cuales una de las técnicas hoy en día empleada es la elevación del piso del seno maxilar mediante el aumento vertical del piso antral. Se reporta el caso de un paciente femenino de 60 años con exodoncias previas, diagnóstico de edentulismo parcial bimaxilar y neumatización del seno maxilar derecho. Se realizó como tratamiento el levantamiento del seno maxilar y la colocación de implantes a nivel postero superior izquierdo empleando la técnica mencionada. Se describe y documenta la premedicación quirúrgica, el momento operatorio, postoperatorio y el seguimiento exitoso del caso luego de seis meses del tratamiento...

The placement of implants in the posterior superior area of the mouth often has to face cases of maxillary ridge atrophy and pneumatization of the maxillary sinus, for which one of the techniques actually used is the elevation of the maxillary sinus floor by vertical increase of the antral floor. It is reported the case of a female patient of 60 years old with previous extractions, bimaxillarypartial edentulism diagnosis and pneumatization of the right maxillary sinus. Treatment was performed at the left posterior superior area for sinus lift and implant placement using the above technique. It is described and documented surgical premedication, surgical approach, postoperative conditions and the successful follow up of the case after six months of the theraphy...

Organizing pneumonia in patients with severe respiratory failure due to novel A (H1N1) influenza.

The authors describe two cases that developed organizing pneumonia (OP) associated with novel influenza A(H1N1) virus. These patients were admitted to intensive care unit (ICU) because of severe respiratory failure. After initial clinical improvement, both patients worsened their condition during their second week of ICU stay, presenting fever, increasing in inflammatory parameters and worsening in oxygen exchange and respiratory mechanics. Chest x-rays and computed tomographies showed an increment on lung infiltrates, given by areas of consolidation and ground glass opacification. Although broad-spectrum antibiotics were administered, patients showed no improvement. All cultures, including bronchoalveolar lavage samples, were negative. In both cases, an open lung biopsy was performed, and histopathological examination of the specimen was compatible with OP. Both patients were successfully treated with high-dose corticoids. The aim of this report is to alert about the possibility of OP associated with novel influenza virus in patients with severe respiratory failure.