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LESSONS LEARNED: Despite the initial optimism for using immune checkpoint inhibition in the treatment of multiple myeloma, subsequent clinical studies have been disappointing. Preclinical studies have suggested that priming the immune system with various modalities in addition to checkpoint inhibition may overcome the relative T-cell exhaustion or senescence; however, in this small data set, radiotherapy with checkpoint inhibition did not appear to activate the antitumor immune response. BACKGROUND: Extramedullary disease (EMD) is recognized as an aggressive subentity of multiple myeloma (MM) with a need for novel therapeutic approaches. We therefore designed a proof-of-principle pilot study to evaluate the synergy between the combination of the anti-PD-L1, avelumab, and concomitant hypofractionated radiotherapy. METHODS: This was a single-arm phase II Simon two-stage single center study that was prematurely terminated because of the COVID-19 pandemic after enrolling four patients. Key eligibility included patients with relapsed/refractory multiple myeloma (RRMM) who had exhausted or were not candidates for standard therapy and had at least one lesion amenable to radiotherapy. Patients received avelumab until progression or intolerable toxicity and hypofractionated radiotherapy to a focal lesion in cycle 2. Radiotherapy was delayed until cycle 2 to allow the avelumab to reach a study state, given the important observation from previous studies that concomitant therapy is needed for the abscopal effect. RESULTS: At a median potential follow-up of 10.5 months, there were no objective responses, one minimal response, and two stable disease as best response. The median progression-free survival (PFS) was 5.3 months (95% confidence interval [CI]: 2.5-7.1 months), and no deaths occurred. There were no grade ≥3 and five grade 1-2 treatment-related adverse events. CONCLUSION: Avelumab in combination with radiotherapy for patients with RRMM and EMD was associated with very modest systemic clinical benefit; however, patients did benefit as usual from local radiotherapy. Furthermore, the combination was very well tolerated compared with historical RRMM treatment regimens.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Mieloma Múltiple , Anciano , Anciano de 80 o más Años , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/radioterapia , Pandemias , Proyectos PilotoRESUMEN
The imbalance between ultrafiltration volume (UF) and vascular refilling is considered a major cause for intradialytic hypotension. Recent studies report a noninvasive method to estimate vascular refilling (VREF ) by determining absolute blood volume (ABV). It was the aim of the study to analyze variations in ABV in a group of hemodialysis (HD) patients and examine VREF . Thirty one stable chronic HD patients were studied, aged 71.07 ± 13.31 years. Dialysis duration and UF requirements were based on physician prescription. VREF was calculated as: VREF = VUF - ΔV where ΔV is ABV variation during dialysis treatment. ABV at the beginning of the dialysis was 6.00 ± 2.39 L (92.82 ± 33.17 ml/kg) and at the end 5.38 ± 2.32 L (82.07 ± 31.41 ml/kg). Prescribed UF was 2.64 ± 0.83 L. Mean VREF was 2.05 ± 0.80 L, with a refilling fraction of 75.75 ± 12.79%. VREF was strongly correlated with UF volume (r2 0.877), and with pre-dialysis volume overload (r2 0.617). Patients under beta-blocker treatment showed significantly lower FREF . ABV measurement is an easy and noninvasive method that allows us to study VREF during HD. We found a strong correlation between VREF and UF.
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BACKGROUND: Vascular refilling occurs to preserve hemodynamic stability during hemodialysis (HD). Recent studies report a feasible and noninvasive method to determine absolute blood volume (ABV), and estimate vascular refilling during HD. The objective of this study is to analyze if lowering dialysate temperature modifies variations in ABV during HD. METHODS: The study was performed in 50 patients under HD. During two different sessions, relative blood volume was assessed using dialysate temperatures of 35.5°C (cool dialysate) and 36.5°C (neutral dialysate). ABV and vascular refilling were calculated using Kron et al methodology. RESULTS: Thirty-nine intradialytic morbid events (IMEs) were observed in 30 patients, 14 under cool dialysate and 25 during neutral dialysate. We did not found statistically differences in ABV or in refilling volume between cool and neutral temperature. When analyzing apart only those patients who presented IME, we observed lower drop in ABV in the 35.5°C dialysate treatments (0.57 L) versus 36.5°C dialysate treatments (0.71 L). When cool dialysate was used, the vascular refilling fraction tended to be higher, but data did not turn statistically significant. CONCLUSIONS: In selected groups of patients the use of cool dialysate induces lower ABV variations that could improve hemodynamic stability during HD treatments.
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Soluciones para Diálisis , Hipotensión , Presión Sanguínea , Volumen Sanguíneo , Humanos , Hipotensión/etiología , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , TemperaturaRESUMEN
To date, an endonasal approach has not been described that combines different incisions to provide exposure of all of the key anatomical structures, allowing for adequate, comprehensive visualization of the nasal architecture including the complete quadrangular cartilage and its extension with the upper lateral cartilages, including the caudal septal border from the ventral border and anterior nasal spine to the anterior septal angle, the scroll, and internal nasal valve.The endonasal approach that Fausto Lopez-Infante designed, the FLI technique, combines several basic known endonasal incisions that together allow excellent access and great visualization of the intranasal surgical field, enables extensive septal work, and preserves the natural anatomy of the dorsum as well as the tip support structures.This technique and approach to nasal surgery are based on an understanding of anatomy, allow standardization of the surgery, and make it reproducible. It is an outstanding option with excellent cosmetic and functional results.
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Rinoplastia , Cartílago , Humanos , Tabique Nasal/cirugíaRESUMEN
The biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P) are interlinked by primary production, respiration and decomposition in terrestrial ecosystems. It has been suggested that the C, N and P cycles could become uncoupled under rapid climate change because of the different degrees of control exerted on the supply of these elements by biological and geochemical processes. Climatic controls on biogeochemical cycles are particularly relevant in arid, semi-arid and dry sub-humid ecosystems (drylands) because their biological activity is mainly driven by water availability. The increase in aridity predicted for the twenty-first century in many drylands worldwide may therefore threaten the balance between these cycles, differentially affecting the availability of essential nutrients. Here we evaluate how aridity affects the balance between C, N and P in soils collected from 224 dryland sites from all continents except Antarctica. We find a negative effect of aridity on the concentration of soil organic C and total N, but a positive effect on the concentration of inorganic P. Aridity is negatively related to plant cover, which may favour the dominance of physical processes such as rock weathering, a major source of P to ecosystems, over biological processes that provide more C and N, such as litter decomposition. Our findings suggest that any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P. These changes would uncouple the C, N and P cycles in drylands and could negatively affect the provision of key services provided by these ecosystems.
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Clima Desértico , Desecación , Ecosistema , Geografía , Suelo/química , Silicatos de Aluminio/análisis , Biomasa , Carbono/análisis , Carbono/metabolismo , Ciclo del Carbono , Arcilla , Cambio Climático , Modelos Teóricos , Nitrógeno/análisis , Nitrógeno/metabolismo , Ciclo del Nitrógeno , Monoéster Fosfórico Hidrolasas/análisis , Monoéster Fosfórico Hidrolasas/metabolismo , Fósforo/análisis , Fósforo/metabolismo , Plantas/metabolismoRESUMEN
When viewing the most famous smiles in history (Figure 1), two constants become apparent: a smooth perioral surface and oral commissures that are turned upward (or horizontal as a minimum). Patients are often fixated on improving both the marionette lines and the downward oral commissures as these distractions are one of the most noticeable areas in the aging face to the average person. In addition, the downward turn of the oral commissures gives an impression of sadness. Unfortunately, the anatomy of this area makes non-surgical treatments less than satisfactory, and unpredictable in many cases. The senior author has developed a novel technique to treat the marionette lines and turn the corner of the mouth upward that has been named the Happy Face treatment. The key for a successful outcome is the assessment of the perioral anatomy and the understanding of the physio dynamics of the jowl to produce a Mona Lisa smile and a Happy Face.
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Técnicas Cosméticas , Cara/anatomía & histología , Músculos Faciales/cirugía , Rejuvenecimiento , Envejecimiento de la Piel , Estética , Músculos Faciales/anatomía & histología , Femenino , Humanos , Resultado del TratamientoRESUMEN
Respiratory immunization is an attractive way to generate systemic and mucosal protective memory responses that are required for preventing mucosally transmitted infections. However, the molecular and cellular mechanisms for controlling memory T cell responses remain incompletely understood. In this study, we investigated the role of respiratory macrophage (MΦ) in regulating CD4 T cell responses to recombinant adenovirus-based (rAd) vaccines. We demonstrated that rAd intranasal (i.n.) vaccination induced migration and accumulation of respiratory MΦ and circulatory monocytes in the mediastinal lymph nodes and lung parenchyma. Under the influence of respiratory MΦ CD4 T cells exhibited slow proliferation kinetics and an increased tendency of generating central memory, as opposed to effector memory, CD4 T cell responses in vitro and in vivo. Correspondingly, depletion of MΦ using clodronate-containing liposome prior to i.n. immunization significantly enhanced CD4 T cell proliferation and increased the frequency of CD4 memory T cells in the airway lumen, demonstrating that MΦ initially serve as a negative regulator in limiting generation of mucosal tissue-resident memory CD4 T cells. However, clodronate-containing liposome delivery following i.n. immunization markedly reduced the frequencies of memory CD4 T cells in the airway lumen and spleen, indicating that respiratory MΦ and potentially circulating monocytes are critically required for maintaining long-term memory CD4 T cells. Collectively, our data demonstrate that rAd-induced mucosal CD4 T memory responses are regulated by respiratory MΦ and/or monocytes at multiple stages.
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Linfocitos T CD4-Positivos/inmunología , Pulmón/inmunología , Macrófagos Alveolares/inmunología , Vacunas Sintéticas/inmunología , Adenoviridae/genética , Animales , Comunicación Celular , Movimiento Celular , Proliferación Celular , Células Cultivadas , Ácido Clodrónico/administración & dosificación , Femenino , Inmunidad Mucosa , Memoria Inmunológica , Macrófagos Alveolares/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , VacunaciónRESUMEN
BACKGROUND AND AIMS: Currently, eradication of Barrett's epithelium is preferably achieved using radiofrequency ablation (RFA) or spray cryoablation (SCA). However, both modalities suffer from drawbacks such as the need for sizing, multiple deployment steps, large controller units (RFA), imprecise dosing and need for gas-venting (SCA). The new Cryoballoon Focal Ablation System (CbFAS) may address these limitations. This study assessed the safety, feasibility, and dose response of the CbFAS in patients with flat Barrett's epithelium with or without dysplasia. PATIENTS AND METHODS: In this multicenter, prospective non-randomized trial, 39 patients were each treated with one or two ablations of 6, 8, or 10 seconds. Symptoms were assessed immediately and 2 days post-cryoablation. Follow-up endoscopy was performed 6-8 weeks post-procedure to assess response. Outcome parameters were incidence of adverse events, pain, esophageal stricture formation, and ablation response by cryogen dose. RESULTS: Of 62 ablations, 56 (10 with 6 seconds, 28 with 8 seconds, 18 with 10 seconds) were successfully performed. Six ablations failed because of device malfunction (n=3) and procedural or anatomic issues (n=3). Median procedure time was 7 minutes (interquartile range [IQR] 4-10). No major adverse events occurred; six patients experienced a minor mucosal laceration requiring no intervention. Mild pain was reported by 27% of patients immediately after cryoablation and by 14% after 2 days. No strictures were evident at follow-up.â Full squamous regeneration was seen in 47 treated areas (6 [60%] of the 6-second areas; 23 [82%] of the 8-second areas; 18 [100%] of 10-second areas). CONCLUSIONS: Focal cryoablation of Barrett's epithelium with the CbFAS is feasible and safe, resulting in squamous regeneration in the majority of patients.
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Esófago de Barrett , Criocirugía , Esofagoscopía , Esófago , Dolor Postoperatorio/diagnóstico , Anciano , Esófago de Barrett/diagnóstico , Esófago de Barrett/cirugía , Criocirugía/efectos adversos , Criocirugía/instrumentación , Criocirugía/métodos , Esofagoscopía/efectos adversos , Esofagoscopía/instrumentación , Esofagoscopía/métodos , Esófago/patología , Esófago/cirugía , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Resultado del TratamientoRESUMEN
Free-living amoebae have been found in soil, air and a variety of aquatic environments, but few studies have been conducted on industrial wastewater and none on wastewater from the textile industry. The aim of this study was to determine the presence and distribution of free-living amoebae in a biological treatment system that treats textile industrial wastewater. Samples were taken from input, aeration tank, sedimentation tank and output. Samples were centrifuged at 1200g for 15min, the sediment was seeded on non-nutritive agar with Enterobacter aerogenes (NNE) and the plates were incubated at 30 and 37°C. Free-living amoebae were present in all stages of the treatment system. The highest number of amoebic isolates was found in the aeration tank and no seasonal distribution was observed during the year. A total of 14 amoeba genera were isolated: Acanthamoeba, Echinamoeba, Korotnevella, Mayorella, Naegleria, Platyamoeba, Saccamoeba, Stachyamoeba, Thecamoeba, Vahlkampfia, Vannella, Vermamoeba, Vexillifera and Willaertia. The most frequently found amoebae were Acanthamoeba and Vermamoeba which were found in all treatment system stages. The constant presence and diversity of free-living amoebae in the treatment system were important findings due to the characteristics of the wastewater from the textile plant in terms of the residue content from colorants, fixers, carriers, surfactants, etc., used in fabric dyeing and finishing processes. The factors that determined the presence and distribution of amoebae in the activated sludge system were their capacity to form cysts, which allowed them to resist adverse conditions; food availability; an average temperature of 27-33°C; dissolved oxygen in average concentrations above 2mg/L, and pH in a range of 5.9-7.1.
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Amoeba/aislamiento & purificación , Residuos Industriales , Industria Textil , Aguas Residuales/parasitología , Amoeba/clasificación , Concentración de Iones de Hidrógeno , México , TemperaturaRESUMEN
Objective: Educators often lack the knowledge and resources to assist students with acquired brain injury (ABI). TeachABI, an education module, was created to help elementary school teachers support students with ABI in classrooms. This study examined the adaptability of TeachABI for high school educators. Methods: A qualitative descriptive study explored high school educators' (n = 9) experiences reviewing TeachABI and its adaptability for high school through semi-structured interviews. The interview guide was informed by implementation and adaptation frameworks. Transcripts were examined using directed content analysis. Results: Teachers felt TeachABI was a good foundation for creating a high school-based education module. Adaptations were highlighted, such as streamlining content (e.g., mental health) and strategies (e.g., supporting test taking), to better meet educator needs. Conclusions: Using implementation science and adaptation frameworks provided a structured approach to explore the adaptive elements of TeachABI. The module was perceived as a suitable platform for teaching high school educators about ABI. Innovation: TeachABI is an innovative, user informed education module, providing a multi-modal (e.g., case study, videos) and replicable approach to learning about ABI. Applying frameworks from different fields provides concepts to consider when tailoring resources to align with educator needs (e.g., grade, class environment) and facilitate innovation uptake.
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Chronic wasting disease (CWD) has become a major concern among those involved in managing wild and captive cervid populations. CWD is a fatal, highly transmissible spongiform encephalopathy caused by an abnormally folded protein, called a prion. Prions are present in a number of tissues, including feces and urine in CWD infected animals, suggesting multiple modes of transmission, including animal-to-animal, environmental, and by fomite. CWD management is complicated by the lack of practical, non-invasive, live-animal screening tests. Recently, there has been a focus on how the volatile odors of feces and urine can be used to discriminate between infected and noninfected animals in several different species. Such a tool may prove useful in identifying potentially infected live animals, carcasses, urine, feces, and contaminated environments. Toward this goal, dogs were trained to detect and discriminate CWD infected individuals from non-infected deer in a laboratory setting. Dogs were tested with novel panels of fecal samples demonstrating the dogs' ability to generalize a learned odor profile to novel odor samples based on infection status. Additionally, dogs were transitioned from alerting to fecal samples to an odor profile that consisted of CWD infection status with a different odor background using different sections of gastrointestinal tracts. These results indicated that canine biodetectors can discriminate the specific odors emitted from the feces of non-infected versus CWD infected white-tailed deer as well as generalizing the learned response to other tissues collected from infected individuals. These findings suggest that the health status of wild and farmed cervids can be evaluated non-invasively for CWD infection via monitoring of volatile metabolites thereby providing an effective tool for rapid CWD surveillance.
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Ciervos , Heces , Odorantes , Enfermedad Debilitante Crónica , Animales , Enfermedad Debilitante Crónica/diagnóstico , Enfermedad Debilitante Crónica/transmisión , Enfermedad Debilitante Crónica/orina , Odorantes/análisis , Heces/química , Priones/análisis , PerrosRESUMEN
Transplantation (KTx) is considered to be the best renal replacement therapy, and improving its outcomes remains a primary challenge. KTx ureteral stenting has been used to prevent urological complications, but there is no consensus on the timing of stent removal, and literature regarding routine ultrasonography after ureteric stent removal (RUSUS) to detect complications is lacking. Point-of-care ultrasound has been gaining drive in the medical community in recent years, including nephrologists. We aimed to define the incidence of urological complications diagnosed with RUSUS, if those findings changed patient's management and ultrasound utility. Contrary to previously published data, in our cohort RUSUS allowed a timely diagnosis and early treatment of urological complications, a key factor for successful transplantation. KTx point-of-care ultrasound is a cost-effective and reproducible test that provides relevant information to guide clinical decisions, seeming most efficient when performed approximately 2 weeks post ureteral stent removal. Interventional nephrologists can promptly perform these examinations, reducing waiting times and improving graft and patient's survival.
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Complicaciones Posoperatorias , Uréter , Humanos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Uréter/diagnóstico por imagen , Uréter/cirugía , Stents , Riñón , UltrasonografíaRESUMEN
This study investigated the novel application of Fe-TiO2-allophane catalysts with 6.0 % w/w of iron oxide and two TiO2 proportions (10 % and 30 % w/w) for degrading atrazine (ATZ) using the heterogeneous dual-effect (HDE) process under sunlight. Comparative analyses with Fe-allophane and TiO2-allophane catalysts were conducted in both photocatalysis (PC) and HDE processes. FTIR spectra reveal the unique hydrous feldspathoids structure of allophane, showing evidence of new bond formation between Si-O groups of allophane clays and iron hydroxyl species, as well as Si-O-Ti bonds that intensified with higher TiO2 content. The catalysts exhibited an anatase structure. In Fe-TiO2-allophane catalysts, iron oxide was incorporated through the substitution of Ti4+ by Fe3+ in the anatase crystal lattice and precipitation on the surface of allophane clays, forming small iron oxide particles. Allophane clays reduced the agglomeration and particle size of TiO2, resulting in an enhanced specific surface area and pore volume for all catalysts. Iron oxide incorporation decreased the band gap, broadening the photoresponse to visible light. In the PC process, TiO2-allophane achieves 90 % ATZ degradation, attributed to radical species from the UV component of sunlight. In the HDE process, Fe-TiO2-allophane catalysts exhibit synergistic effects, particularly with 30 % w/w TiO2, achieving 100 % ATZ degradation and 85 % COD removal, with shorter reaction time as TiO2 percentage increased. The HDE process was performed under less acidic conditions, achieving complete ATZ degradation after 6 h without iron leaching. Consequently, Fe-TiO2-allophane catalysts are proposed as a promising alternative for degrading emerging pollutants under environmentally friendly conditions.
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Classical swine fever (CSF) remains one of the most economically significant viral diseases affecting domestic pigs and wild boars worldwide. To develop a safe and effective vaccine against CSF, we have constructed a triple gene-deleted pseudorabies virus (PRVtmv)-vectored bivalent subunit vaccine against porcine circovirus type 2b (PCV2b) and CSFV (PRVtmv+). In this study, we determined the protective efficacy of the PRVtmv+ against virulent CSFV challenge in pigs. The results revealed that the sham-vaccinated control group pigs developed severe CSFV-specific clinical signs characterized by pyrexia and diarrhea, and became moribund on or before the seventh day post challenge (dpc). However, the PRVtmv+-vaccinated pigs survived until the day of euthanasia at 21 dpc. A few vaccinated pigs showed transient diarrhea but recovered within a day or two. One pig had a low-grade fever for a day but recovered. The sham-vaccinated control group pigs had a high level of viremia, severe lymphocytopenia, and thrombocytopenia. In contrast, the vaccinated pigs had a low-moderate degree of lymphocytopenia and thrombocytopenia on four dpc, but recovered by seven dpc. Based on the gross pathology, none of the vaccinated pigs had any CSFV-specific lesions. Therefore, our results demonstrated that the PRVtmv+ vaccinated pigs are protected against virulent CSFV challenge.
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Circovirus , Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Herpesvirus Suido 1 , Linfopenia , Trombocitopenia , Vacunas Virales , Porcinos , Animales , Herpesvirus Suido 1/genética , Vacunas Virales/genética , Proteínas del Envoltorio Viral , Anticuerpos Antivirales , Sus scrofa , DiarreaRESUMEN
BACKGROUND: The authors present a retrospective, comparative, and analytical cohort study, that aimed to prove the utility of unilateral or asymmetrical bony wedge resection to straighten the twisted nose as applied in let-down and push-down methods. The study involved objective angle measurements preoperatively and postoperatively on frontal view photographs. METHODS: Preoperative and postoperative angle measurements were made on frontal view photographs of 78 patients with twisted noses classified as type C and type I. Angles of deviation were obtained using Scion Image software, measured in degrees. Statistical analysis was performed using Excel v15.13.3. RESULTS: Forty-two patients had twisted nose type C and 28 patients had twisted nose type I. The mean age was 19 years. There was an 81% improvement ratio for twisted nose type C and 79% for twisted nose type I, and the angle correction for each type of nasal deformity was statistically significant ( P < 0.01). The majority of postoperative results were classified as excellent to good, with the exception of four cases with bad outcomes, including two patients with type C and two with type I deviations. CONCLUSIONS: Unilateral or asymmetrical bony wedge resection is a modification of the let-down rhinoplasty technique. This study demonstrates statistically significant improvements in straightening twisted noses among patients with or without preoperative hump and preserving the nasal dorsum. The authors found this modification better suited for type C deviations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
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Rinoplastia , Humanos , Adulto Joven , Adulto , Rinoplastia/métodos , Estudios de Cohortes , Estudios Retrospectivos , Tabique Nasal/cirugía , Resultado del Tratamiento , Nariz/cirugíaRESUMEN
BACKGROUND: Although relationship between dialysate sodium concentration and hemodynamic stability has been well studied over the years, outcomes of absolute blood volume (ABV) maintenance and vascular refilling volume (Vref ) modifications were not included, as its analysis has not been easily accessible to direct investigation. However, recent studies report a simple and feasible methodology to assess ABV and Vref during hemodialysis (HD) treatments. It is the aim of this study to analyze whether sodium concentration in dialysate modifies ABV drop and Vref . METHODS: The study was performed in 19 patients under HD. During three different sessions, sodium concentration in dialysate was randomized to three different profiles: low sodium concentration (LNa, 138 mEq/L), neutral sodium concentration (NNa, 140 mEq/L), and high sodium concentration (HNa, 143 mEq/L). ABV and Vref were calculated using Kron et al methodology. RESULTS: Predialysis values of the measured parameters showed similar results for the three profiles. Sodium concentration showed an effect on ABV drop, Vref, and vascular refilling fraction (Fref ). Pair-wise comparison revealed mean ABV decreased 0.21 L less when using HNa profile versus LNa profile (p = 0.027), a mean Vref increase of 0.39 L (p = 0.038), and a mean Fref increase of 9.94% (p = 0.048). CONCLUSIONS: This study shows that the use of HNa profiles increases Vref and Fref and reduces ABV drop during dialysis treatments when compared to LNa profiles.
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Soluciones para Diálisis , Sodio , Volumen Sanguíneo , Humanos , Diálisis Renal/métodosRESUMEN
BACKGROUND: ß-Blockers are the most frequently prescribed cardioprotective drugs in hemodialysis (HD) patients, despite their weak evidence. We sought to evaluate the effects of ß-blockers on vascular refilling during HD treatments and examine whether carvedilol, for being noncardioselective and poorly dialyzable, associates more impact than others. METHODS: The study was performed in a cohort of maintenance HD patients from a tertiary center. All patients had previous ß-blocker prescription. We conducted a prospective crossover study and measured vascular refilling volume (Vref) and vascular refilling fraction (Fref) in 2 circumstances: under ß-blocker treatment (ßb profile) and without ß-blocker effect (non-ßb profile). RESULTS: Twenty patients were included, 10 of whom were treated with carvedilol. Predialysis values were comparable between the 2 profiles. Although the ßb profile showed lower Vref and higher ABV drop, these differences did not reach statistical significance. Data showed an increase in Fref in the non-ßb profile (70.01 ± 6.80% vs. 63.14 ± 11.65%; p = 0.015). The ßb profile associated a significantly higher risk of intradialytic hypotension (IDH) (risk ratio 2.40; 95% CI: 1.04-5.55). When analyzing separately the carvedilol group, patients dialyzed under drug effect experienced a significant impairment in Vref, Fref, and refilling rate. CONCLUSIONS: Administering ß-blockers before HD associated a higher risk of IDH and a decrease in Fref. Patients dialyzed under carvedilol effect showed an impaired refilling, probably related to its noncardioselectivity and lower dializability.
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Antagonistas Adrenérgicos beta , Carvedilol , Diálisis Renal , Antagonistas Adrenérgicos beta/efectos adversos , Carvedilol/efectos adversos , Estudios Cruzados , Humanos , Hipotensión , Estudios ProspectivosRESUMEN
BACKGROUND: High-risk birth is a public health problem that generates atypical parenting practices. This study aimed to identify these practices to construct and validate a scale to measure parenting factors and attitudes in children with high-risk birth parents. METHODS: The instrument was applied to an intentional non-probabilistic sample of 701 parents of children with high-risk births (age range 17-64 years). The scale consists of 56 items, each with five Likert-type response options. RESULTS: As a result of the factor analysis with Varimax rotation, the final version was divided into two subscales: factors and attitudes associated with parenting skills. In the first, with 36 items and six factors (low educational skills, overprotection, and permissive parenting, dissatisfaction with the parental role, stress in raising a child with a high-risk birth, tri-generational disapproval of the parental role, and positive support from the extended family), a Cronbach's alpha value of 0.90 was obtained, explaining 53.16 of the variance. In the second subscale, with 30 items grouped in four factors (parenting beliefs, negative coping with high-risk birth, self-validation in parenting, and parental resilience to the experience of high-risk birth parenting), a Cronbach's alpha of 0.82 was obtained, explaining 48.08 of the variance. CONCLUSIONS: We suggest that this scale be applied together with others that measure theoretically related variables.
INTRODUCCIÓN: El nacimiento de alto riesgo es un problema de salud pública que genera prácticas de crianza atípicas. El objetivo de este estudio fue identificar estas prácticas para construir y validar una escala para medir factores y actitudes de la crianza en los padres de niños con nacimiento de alto riesgo. MÉTODOS: La escala consta de 56 reactivos con cinco opciones de respuesta tipo Likert. El instrumento se aplicó a una muestra no probabilística de 701 padres de niños con nacimiento de alto riesgo (rango de edad: 17-64 años). RESULTADOS: Como resultado del análisis factorial con rotación Varimax, la versión final se dividió en dos subescalas: factores y actitudes asociados con la crianza. En la primera, con 36 reactivos y seis factores (bajas habilidades educativas, sobreprotección y crianza permisiva, insatisfacción ante el rol parental ejercido, estrés ante la crianza de un niño con nacimiento de alto riesgo, desaprobación trigeneracional en el rol parental y apoyo positivo de la familia extensa), se obtuvo un valor alfa de Cronbach de 0.90, explicando el 53.16 de la varianza. En la segunda subescala, con 30 reactivos y cuatro factores (creencias ante la crianza, afrontamiento negativo ante el nacimiento de alto riesgo, autovalidación en la crianza y resiliencia parental ante la experiencia de la crianza y el nacimiento de alto riesgo), se obtuvo un valor alfa de Cronbach de 0.82, explicando el 48.08 de la varianza. CONCLUSIONES: Se sugiere la aplicación de esta escala junto con otras que midan variables teóricamente relacionadas.
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Responsabilidad Parental , Padres , Adolescente , Adulto , Actitud , Niño , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
In the United States non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting an estimated 80 to 100 million people. It occurs in every age group, but predominantly in people with risk factors such as obesity and type 2 diabetes. NAFLD is marked by fat accumulation in the liver leading to liver inflammation, which may lead to scarring and irreversible damage progressing to cirrhosis and liver failure. In animal models, genetic ablation of the protein G0S2 leads to alleviation of liver damage and insulin resistance in high fat diets. The research presented in this paper aims to aid in rational based drug design for the treatment of NAFLD by providing a pathway for a solution state NMR structure of G0S2. Here we describe the expression of G0S2 in an E. coli system from two different constructs, both of which are confirmed to be functionally active based on the ability to inhibit the activity of Adipose Triglyceride Lipase. In one of the constructs, preliminary NMR spectroscopy measurements show dominant alpha-helical characteristics as well as resonance assignments on the N-terminus of G0S2, allowing for further NMR work with this protein. Additionally, the characterization of G0S2 oligomers are outlined for both constructs, suggesting that G0S2 may defensively exist in a multimeric state to protect and potentially stabilize the small 104 amino acid protein within the cell. This information presented on the structure of G0S2 will further guide future development in the therapy for NAFLD.
Asunto(s)
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Espectroscopía de Resonancia Magnética , Enfermedad del Hígado Graso no Alcohólico/enzimología , Animales , HumanosRESUMEN
Free-living amoebae are widely distributed in aquatic environments and their hygienic, medical and ecological relationships to man are increasingly important. The purpose of this study was to isolate free-living amoebae from water-hyacinth root (Eichhornia crassipes) and the water of an urban lake in Mexico City. Five grams of wet root were seeded on non-nutritive agar with Enterobacter aerogenes (NNE). Water samples were concentrated by centrifugation at 1200g for 15min and the pellet was seeded on NNE. Of the 16 isolated genera, 10 were detected in both habitats. The most frequent were Vannella in root and Acanthamoeba and Naegleria in water. The total number of isolates and genera isolated from root was higher than that isolated from water. The differences between root and water are probably due to the morphological characteristics of water-hyacinth root, which provides a large habitat and refuge area for many organisms.