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BACKGROUND: The SunSafe Student Ambassador Program (SSSAP) in Australia uses the peer-to-peer learning environment to educate high-school students about sun-safety. AIMS: To assess whether the SSSAP would improve knowledge, attitudes and behaviours towards sun safety in high-school students and whether this would be sustained at 3 months. METHODS: An assessment survey was delivered before, immediately after and 3 months after participation in the SSSAP in 2019. RESULTS: In total, 503 participants completed the pre-presentation survey, 274 completed the post-presentation survey, and 218 completed both. Immediately following presentation, the total composite score for all 18 knowledge questions increased from a mean ± SD of 11.8 ± 3.5 to 13.8 ± 4.7 (P < 0.001). There was strong evidence for an improvement in one attitude-based question 'Is it healthy to have a tan?' (P < 0.01) and one behaviour question about wearing sunscreen daily (P = 0.02). After 3 months, 235 students were matched to their pre-presentation survey. The composite score of all knowledge questions had improved from 11.2 ± 3.5 to 12.1 ± 4.5 (out of a total of 18) (P < 0.01). There was also an improvement in two attitude questions 'Do you feel better when you have a tan?' (P = 0.03) and 'Is it healthy to have a tan?' (very strong evidence: P < 0.001), and evidence for a reduction in time spent outdoors on a weekday (P = 0.04). CONCLUSION: The SSSAP was associated with improvements in knowledge, attitude and behaviour towards sun safety immediately and at 3 months post-presentation. Further research is required to determine whether these positive effects are sustained and whether they ultimately reduce skin cancers.
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Baño de Sol , Protectores Solares , Humanos , Australia , Conocimientos, Actitudes y Práctica en Salud , Estudios Prospectivos , Estudiantes , Protectores Solares/uso terapéuticoRESUMEN
For patients who do not achieve adequate disease control on biologic monotherapy, or monotherapy with an oral-systemic agent such as methotrexate, combination biologic therapy may be considered. To the best of our knowledge, we report the first case assessing the safety and efficacy of the combination of an interleukin-23 (IL-23) inhibitor (risankizumab) with a tumour necrosis factor-α (TNF-α) inhibitor (golimumab) in the treatment of psoriasis and psoriatic arthritis. After twelve months of treatment with risankizumab and golimumab, our patient experienced a significant improvement in his psoriasis and psoriatic arthritis without any adverse effects to date.
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Anticuerpos Monoclonales/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Artritis Psoriásica/complicaciones , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Afecciones Crónicas Múltiples , Psoriasis/complicaciones , Calidad de VidaRESUMEN
Ischaemic post-conditioning (IPoC) is a clinical applicable procedure to reduce reperfusion injury. Non-responsiveness to IPoC possibly caused by co-morbidities limits its clinical attractiveness. We analysed differences in the expression of mitochondrial proteins between IPoC responder (IPoC-R) and non-responder (IPoC-NR). Eighty rats were randomly grouped to sham, ischaemia/reperfusion (I/R), IPoC or ischaemic pre-conditioning (IPC, as positive cardioprotective intervention) in vivo. Infarct sizes were quantified by plasma troponin I levels 60 minutes after reperfusion. After 7 days, rats were sacrificed and left ventricular tissue was taken for post hoc analysis. The transcriptome was analysed by qRT-PCR and small RNA sequencing. Key findings were verified by immunoblots. I/R increased plasma troponin I levels compared to Sham. IPC reduced troponin I compared to I/R, whereas IPoC produced either excellent protection (IPoC-R) or no protection (IPoC-NR). Twenty-one miRs were up-regulated by I/R and modified by IPoC. qRT-PCR analysis revealed that IPoC-R differed from other groups by reduced expression of arginase-2 and bax, whereas the mitochondrial uncoupling protein (UCP)-2 was induced in IPC and IPoC-R. IPoC-R and IPoC-NR synergistically increased the expression of non-mitochondrial proteins like VEGF and SERCA2a independent of the infarct size. Cardiac function was more closely linked to differences in mitochondrial proteins than on regulation of calcium-handling proteins. In conclusion, healthy rats could not always be protected by IPoC. IPoC-NR displayed an incomplete responsiveness which is reflected by different changes in the mitochondrial transcriptome compared to IPoC-R. This study underlines the importance of mitochondrial proteins for successful long-term outcome.
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Perfilación de la Expresión Génica , Poscondicionamiento Isquémico , Mitocondrias/genética , Mitocondrias/metabolismo , Transcriptoma , Animales , Biomarcadores , Biología Computacional/métodos , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Poscondicionamiento Isquémico/métodos , MicroARNs/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/diagnóstico , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Ratas , Troponina I/metabolismoRESUMEN
Proprotein convertase subtilisin kexin type 9 (PCSK9) is in the focus of cardiovascular research due to its role in hepatic low density lipoprotein (LDL) clearance. However, extrahepatic expression of PCSK9 such as in cardiomyocytes and its regulation by oxidized LDL (oxLDL) put notion on extrahepatic effects of PCSK9 as well. This study was aimed to reveal the role of PCSK9 in oxLDL-dependent regulation of cardiomyocyte function. Adult rat and mouse ventricular cardiomyocytes and isolated perfused hearts were used. OxLDL was applied to increase PCSK9 expression in cardiomyocytes. Cell function was analyzed by load-free cell shortening as well as left ventricular developed pressure of isolated hearts. OxLDL decreased shortening in wild-type-derived mouse cardiomyocytes but not in those isolated from PCSK9 knockout mice. Overexpression of human PCSK9 in rat cardiomyocytes reduced shortening in the absence of oxLDL. Addition of recombinant PCSK9 mimicked these effects. In cardiomyocytes, oxLDL induced PCSK9 release into the supernatant. Inhibition of PCSK9 by Pep 2-8 or alirocumab attenuated the oxLDL-induced loss of cardiomyocyte shortening. Cardiomyocytes express surfeit locus protein 4 (SURF-4), a protein required for PCSK9 secretion in human embryonic kidney cells (HEK 293 T), and silencing of SURF-4 reduced the oxLDL effects on cardiomyocytes. In isolated perfused rat hearts PCSK9 inhibition by alirocumab improved the function. In addition, left ventricular function of isolated hearts from PCSK9 knockout mice was increased under basal conditions as well as at 10 min and 120 min of reperfusion following 45 min of ischemia. Collectively, the data show that cardiomyocytes express and release PCSK9 that acts in an autocrine way on cardiomyocytes and impairs their function.
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Comunicación Autocrina , Miocitos Cardíacos/enzimología , Proproteína Convertasa 9/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Comunicación Autocrina/efectos de los fármacos , Células Hep G2 , Humanos , Preparación de Corazón Aislado , Lipoproteínas LDL/farmacología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Contracción Miocárdica , Miocitos Cardíacos/efectos de los fármacos , Inhibidores de PCSK9 , Proproteína Convertasa 9/genética , Ratas Wistar , Inhibidores de Serina Proteinasa/farmacología , Transducción de Señal , Función Ventricular Izquierda , Presión VentricularRESUMEN
The leading cause of death in pulmonary arterial hypertension (PAH) is right ventricular (RV) failure (RVF). Reactive oxygen species (ROS) have been suggested to play a role in the development of RV hypertrophy (RVH) and the transition to RVF. The hydrogen peroxide-generating protein p66shc has been associated with left ventricular (LV) hypertrophy but its role in RVH is unclear. The purpose of this study was to determine whether genetic deletion of p66shc affects the development and/or progression of RVH and RVF in the pulmonary artery banding (PAB) model of RV pressure overload. The impact of p66shc on mitochondrial ROS formation, RV cardiomyocyte function, as well as on RV morphology and function were studied three weeks after PAB or sham operation. PAB in wild type mice did not affect mitochondrial ROS production or RV cardiomyocyte function, but induced RVH and impaired cardiac function. Genetic deletion of p66shc did also not alter basal mitochondrial ROS production or RV cardiomyocyte function, but impaired RV cardiomyocyte shortening was observed following PAB. The development of RVH and RVF following PAB was not affected by p66shc deletion. Thus, our data suggest that p66shc-derived ROS are not involved in the development and progression of RVH or RVF in PAH.
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Cardiomegalia/metabolismo , Ventrículos Cardíacos/metabolismo , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/metabolismo , Animales , Cardiomegalia/etiología , Células Cultivadas , Ventrículos Cardíacos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias Cardíacas/metabolismo , Miocitos Cardíacos/metabolismo , Hipertensión Arterial Pulmonar/complicaciones , Especies Reactivas de Oxígeno/metabolismo , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/genéticaRESUMEN
BACKROUND: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak. METHODS: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher. RESULTS: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1% (95% confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95% CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95% CI, 13.0 to 23.2), whereas 100% of these vaccinees (95% CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95% CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation,0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation,-0.06; P=0.43). CONCLUSIONS: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9% of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students. (Funded by Princeton University and others.).
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Brotes de Enfermedades/prevención & control , Meningitis Meningocócica/inmunología , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo B/inmunología , Anticuerpos Antibacterianos/sangre , Femenino , Humanos , Masculino , Meningitis Meningocócica/epidemiología , Meningitis Meningocócica/prevención & control , New Jersey/epidemiología , Estudios Seroepidemiológicos , Estados Unidos/epidemiología , Universidades , Adulto JovenRESUMEN
BACKGROUND: The BD MAX™ Enteric Bacterial Panel (BDM-EBP) is designed and FDA-cleared to detect Salmonella, Shigella, Campylobacter, and Shiga toxin genes stx1/2 from stool samples. However, rectal swabs, which are not FDA-cleared for clinical testing with the BDM-EBP, are common specimens received from pediatric patients for enteric pathogen testing. The purpose of this study was to evaluate the ability of the BDM-EBP to detect stool pathogens from rectal swabs. METHODS: Routine cultures, Shiga toxin testing, and molecular testing with BDM-EBP were performed on 272 sequential rectal swabs collected from August 2015 to December 2015. Discrepant test results were resolved using Verigene® Enteric Pathogens Nucleic Acid Test (EP). 36 challenge samples (13 Salmonella spp., 3 Shigella spp., 10 Campylobacter spp., and 10 Shiga toxin positive Escherichia coli) were tested using reference strains (American Type Culture Collection) and previous patient isolates diluted to103-104 cfu/ml in saline then added to Sample Buffer Tube (SBT) with negative stool matrix delivered via a swab. Limit of detection testing was performed by serial 10 fold dilutions in saline then added to SBT with negative stool matrix provided via a swab. RESULTS: A total of 272 rectal swab specimens were evaluated and 89 were positive by culture and/or MAX EBP. All discrepant results were BDM-EBP positive and culture negative. 21 of 31 (68%) of the apparent false positive BDM-EBP discrepant results resolved as positive with Nanosphere's Verigene® EP. After resolution of the discordant results, the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are as follows for each target: Salmonella (n = 4) 100%, PPA and 100%, NPA; Shigella (n = 79) 100%, PPA and 95.3%, NPA; Campylobacter (n = 4) 100%, PPA and 99.6%, NPA; and Shiga toxin producing organisms (n = 2) 100%, PPA and 100%, NPA. 8.8% of the patient samples did not initially yield a result on the BDM-System. Upon repeat, half of the problematic samples resolved, and 4.4% of the total specimen tested did not yield a result. All organisms in the challenge samples were detected. Limits of detection for BDM-EBP testing of rectal swabs were as follows (in cfu/ml in SBT): Salmonella-1.44 × 102; Shigella-5.10 × 100; Campylobacter-1.51 × 101; and Shiga Toxin-1.13 ×103. CONCLUSION: Rectal swabs are acceptable samples for detecting Salmonella, Shigella, Campylobacter, and Shiga toxin using BDM-EBP.
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BACKGROUND: Conventional bacterial stool culture is one of the more time-consuming tests in a routine clinical microbiology laboratory. In addition, less than 5 % of stool cultures yield positive results. A molecular platform, the BD MAX™ System (BD Diagnostics, Sparks, MD) offers the potential for significantly more rapid results and less hands-on time. Time-motion analysis of the BD MAX Enteric Bacterial Panel (EBP) (BD Diagnostics, Quebec, Canada) on the BD MAX System was compared to conventional stool culture in the microbiology laboratory of a tertiary care pediatric hospital. METHODS: The process impact analysis of time-motion studies of conventional cultures were compared to those of EBP with 86 stool specimens. Sample flow, hands-on time, processing steps, and overall turnaround time were determined and analyzed. Data were obtained and analyzed from both standard operating procedures and direct observation. A regression analysis was performed to ensure consistency of measurements. Time and process measurements started when the specimens were logged into the accessioning area of the microbiology laboratory and were completed when actionable results were generated. RESULTS: With conventional culture, negative culture results were available from 41:14:27 (hours:minutes:seconds) to 54:17:19; with EBP, positive and negative results were available from 2:28:40 to 3:33:39. CONCLUSIONS: This study supports the suggestion that use of the EBP to detect commonly encountered stool pathogens can result in significant time savings and a shorter time-to-result for patients with acute bacterial diarrhea.
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A large fraction of submicron atmospheric aerosol particles contains both organic material and inorganic salts. As the relative humidity cycles in the atmosphere and the water content of the particles correspondingly changes, these mixed particles can undergo a range of phase transitions, possibly including liquid-liquid phase separation. If liquid-liquid phase separation occurs, the gas-particle partitioning of atmospheric semivolatile organic compounds, the scattering and absorption of solar radiation, and the reactive uptake of gas species on atmospheric particles may be affected, with important implications for climate predictions. The actual occurrence of liquid-liquid phase separation within individual atmospheric particles has been considered uncertain, in large part because of the absence of observations for real-world samples. Here, using optical and fluorescence microscopy, we present images that show the coexistence of two noncrystalline phases for real-world samples collected on multiple days in Atlanta, GA as well as for laboratory-generated samples under simulated atmospheric conditions. These results reveal that atmospheric particles can undergo liquid-liquid phase separations. To explore the implications of these findings, we carried out simulations of the Atlanta urban environment and found that liquid-liquid phase separation can result in increased concentrations of gas-phase NO(3) and N(2)O(5) due to decreased particle uptake of N(2)O(5).
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Centrosomes and spindle pole bodies (SPBs) are important for mitotic spindle formation and serve as cellular signaling platforms. Although centrosomes and SPBs differ in morphology, many mechanistic insights into centrosome function have been gleaned from SPB studies. In the fission yeast Schizosaccharomyces pombe, the α-helical protein Ppc89, identified based on its interaction with the septation initiation network scaffold Sid4, comprises the SPB core. High-resolution imaging has suggested that SPB proteins assemble on the Ppc89 core during SPB duplication, but such interactions are undefined. Here, we define a connection between Ppc89 and the essential pericentrin Pcp1. Specifically, we found that a predicted third helix within Ppc89 binds the Pcp1 pericentrin-AKAP450 centrosomal targeting (PACT) domain complexed with calmodulin. Ppc89 helix 3 contains similarity to present in the N-terminus of Cep57 (PINC) motifs found in the centrosomal proteins fly SAS-6 and human Cep57 and also to the S. cerevisiae SPB protein Spc42. These motifs bind pericentrin-calmodulin complexes and AlphaFold2 models suggest a homologous complex assembles in all four organisms. Mutational analysis of the S. pombe complex supports the importance of Ppc89-Pcp1 binding interface in vivo. Our studies provide insight into the core architecture of the S. pombe SPB and suggest an evolutionarily conserved mechanism of scaffolding pericentrin-calmodulin complexes for mitotic spindle formation.
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Centrosoma , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Huso Acromático , Cuerpos Polares del Huso , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Cuerpos Polares del Huso/metabolismo , Centrosoma/metabolismo , Huso Acromático/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Antígenos/metabolismo , Calmodulina/metabolismo , Unión ProteicaRESUMEN
CASE: A 10-year-old boy with osteosarcoma of the left distal femur underwent resection with compressive osseointegration endoprosthetic reconstruction, gradually resulting in a 4.5-cm leg-length difference with significant predicted progression. Two years after resection, he underwent right distal femur and proximal tibia epiphysiodesis and placement of a left femoral magnetic lengthening nail. At 2 years after lengthening and skeletal maturity, the patient has symmetric limb lengths, no pain, and returned to sports. CONCLUSION: A magnetic lengthening nail with contralateral epiphysiodesis is a viable option for correcting limb-length discrepancy after distal femur endoprosthetic reconstruction in a pediatric patient.
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Neoplasias Óseas , Procedimientos de Cirugía Plástica , Masculino , Humanos , Niño , Extremidad Inferior , Fémur/cirugía , Neoplasias Óseas/cirugía , Fenómenos MagnéticosRESUMEN
AIM: We conducted a systematic review and evidence gap mapping to explore the existing supportive care interventions and their impact on well-being outcomes for melanoma patients and caregivers. METHODS: We searched MEDLINE, Embase, Web of Science Index Medicus, CINAHL, Lilacs, CENTRAL (Cochrane Library) and PsycINFO in December 2022, including interventional studies assessing the effectiveness of any supportive care intervention among melanoma patients and/or their caregivers. FINDINGS: Twenty studies were included in this review. These studies consisted of randomised controlled trials (n = 11, 55%), pre-post studies (n = 7, 35%) and quasi-experimental trials (n = 2, 10%). All studies originated from high-income countries and focused primarily on melanoma patients, with no studies identified that focused solely on caregivers. Educational interventions were the most common (n = 7, 35%), followed by psychoeducational interventions (n = 6, 30%) and psychotherapeutic interventions (n = 4, 20%). Nearly all included studies (n = 18, 90%) reported a positive effect of the intervention on the primary outcome of interest; however, most studies (n = 17, 85%) were judged to be at moderate or high risk of bias. Due to heterogeneity of study designs, intervention characteristics and outcome measures, meta-analysis was not conducted. IMPLICATIONS: Supportive care interventions have positive impacts on melanoma patient well-being outcomes, while being acceptable and feasible to conduct. More research is needed regarding supportive care interventions for melanoma caregivers. Future research should focus on eliminating sources of bias through rigorous methodology, with the development of standardised outcome measures for psychosocial outcomes to facilitate future meta-analyses.
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Cuidadores , Melanoma , Humanos , Cuidadores/psicología , Melanoma/terapia , Sistemas de Apoyo Psicosocial , SesgoRESUMEN
Significance: Uncoupling proteins (UCPs) are a family of proteins that allow proton leakage across the inner mitochondrial membrane. Although UCP1, also known as thermogenin, is well known and important for heat generation in brown adipose tissue, striated muscles express two distinct members of UCP, namely UCP2 and UCP3. Unlike UCP1, the main function of UCP2 and UCP3 does not appear to be heat production. Recent Advances: Interestingly, UCP2 is the main isoform expressed in cardiac tissues, whereas UCP3 is the dominant isoform in skeletal muscles. In the past years, researchers have started to investigate the regulation of UCP2 and UCP3 expression in striated muscles. Furthermore, concepts about the proposed functions of UCP2 and UCP3 in striated muscles are developed but are still a matter of debate. Critical Issues: Potential functions of UCP2 and UCP3 in striated muscles include a role in protection against mitochondria-dependent oxidative stress, as transporter for pyruvate, fatty acids, and protons into and out of the mitochondria, and in metabolic sensing. In this context, the different isoform expression of UCP2 and UCP3 in the skeletal and cardiac muscle may be related to different metabolic requirements of the two organs. Future Directions: The level of expression of UCP2 and UCP3 in striated muscles changes in different disease stages. This suggests that UCPs may become drug targets for therapy in the future. Antioxid. Redox Signal. 37, 324-335.
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Canales Iónicos , Proteínas Mitocondriales , Tejido Adiposo Pardo/metabolismo , Canales Iónicos/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas Desacopladoras Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , ARN Mensajero/metabolismo , Proteína Desacopladora 2/metabolismo , Proteína Desacopladora 3/genética , Proteína Desacopladora 3/metabolismoRESUMEN
BACKGROUND: The main treatment of primary cutaneous melanoma is surgery. This review aims to assess the width of excision margin that minimises the risk of adverse outcome from surgery, locoregional recurrence, distant recurrence, and death. METHODS: PRISMA guidelines were followed. MEDLINE, EMBASE, and four other databases were searched by using the term "melanoma", "margin", and limiting the search to randomised clinical trials (RCTs). RESULTS: Seven RCTs involving 4579 patients data were analysed. No statistically significant difference was found in locoregional recurrence RR 1.09 (95%CI 0.98-1.22, p = 0.12), local recurrence RR 1.20 (95%CI 0.66-2.21, p = 0.55), in-transit metastasis RR1.30 (95%CI 0.86-1.97, p = 0.21), regional nodal metastasis RR 1.04 (95%CI 0.91-1.18, p = 0.56), distant metastasis RR 0.95 (95%CI 0.72-1.24, p = 0.68), death RR 1.00 (95%CI 0.93-1.07, p = 0.97), death from melanoma RR 1.11 (95%CI 0.96-1.28, p = 0.16), wound infection RR 1.22 (95%CI 0.68-2.17, p = 0.50), and wound dehiscence RR 0.96 (95%CI 0.54-1.71, p = 0.88) when narrow (1-2 cm) versus wide (3-5 cm) excision margins were compared. In contrast, patients with narrow excision margins had a significant reduction in complex surgical reconstruction RR 0.30 (95%CI 0.19-0.49, p < 00001). When studies were excluded because of high risk of bias the only significant difference was death due to melanoma RR 1.25 (95%CI1.01-1.55, P = 0.04). CONCLUSIONS: No significant difference between narrow and wide excision margins in locoregional or distant recurrence, metastasis, death, or death due to melanoma. Wide margins (2-5 cm) increased the need for surgical reconstruction. Further studies are needed to assess optimal excision margins with regards to Breslow thickness and other prognostic factors and are in progress.
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Márgenes de Escisión , Melanoma/patología , Melanoma/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Humanos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Melanoma Cutáneo MalignoRESUMEN
Preterm birth is a major contributor to neonatal mortality and morbidity. While the causes of preterm birth remain incompletely understood, infection is a major risk factor, and chorioamnionitis is commonly observed. Chorioamnionitis is characterized by inflammation and neutrophil infiltration of the fetal membranes (FM). We recently reported that human FMs which had been exposed to low levels of bacterial lipopolysaccharide (LPS) recruit neutrophils and activate them, increasing their secretion of pro-inflammatory cytokines, degranulation of myeloperoxidase (MPO), and release of neutrophil extracellular traps (NETs). Herein, we demonstrate that conditioned media (CM) from viral dsRNA (Poly(I:C))-stimulated FMs also increased neutrophil migration, and induced the secretion of inflammatory IL-8 and the release of NETs. Furthermore, CM from FMs stimulated by a combination of bacterial LPS and Poly(I:C) augmented neutrophil NET release, compared to CM from FMs stimulated with either Poly(I:C) or LPS alone. NETs induced by FMs exposed to Poly(I:C), with or without LPS, were released and degraded quicker than those induced by resting or LPS-stimulated FM-CM. These findings indicate that FMs exposed to viral dsRNA promote neutrophil recruitment, activation and NET formation, similar to FMs exposed to bacterial LPS alone. However, in response to FM polymicrobial stimulation the levels and kinetics of NET release are augmented. This work builds upon our understanding of how infections at the maternal-fetal interface may affect neutrophil function.
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Corioamnionitis/inmunología , Membranas Extraembrionarias/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Nacimiento Prematuro/inmunología , Células Cultivadas , Quimiotaxis/inmunología , Corioamnionitis/microbiología , Corioamnionitis/patología , Medios de Cultivo Condicionados/metabolismo , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Membranas Extraembrionarias/citología , Membranas Extraembrionarias/microbiología , Membranas Extraembrionarias/patología , Femenino , Humanos , Lipopolisacáridos/inmunología , Activación Neutrófila , Neutrófilos , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/patología , Nacimiento Prematuro/microbiología , Nacimiento Prematuro/patología , Cultivo Primario de Células , ARN Bicatenario , ARN Viral/inmunologíaRESUMEN
BACKGROUND: Maintaining normocapnia during mechanical ventilation in anesthetized children during laparoscopic surgeries is highly recommended. There is a debate regarding the use of capnography (ETCO2) as a trend monitor for evaluation of arterial carbon dioxide levels (PaCO2). We analyzed the relationship between ETCO2 and PaCO2 with time in elective pediatric laparoscopic surgeries. METHODS: This study was a prospective observational cohort analysis of 116 paired comparisons between PaCO2 and ETCO2 computed from 29 children (ASA I, 12-72 months). Arterial blood samples were withdrawn before, at 15 minutes and 30 minutes during pneumoperitoneum and 1 minute after deflation. ETCO2 value was recorded simultaneously, while arterial blood was withdrawn. PaCO2-ETCO2 relationship was evaluated by Pearson's correlation coefficients and Bland Altman Method of agreement. RESULTS: Out of the 116 comparisons analyzed, a PaCO2-ETCO2 difference beyond 0 to ≤ 5 mmHg was recorded in 71 comparisons (61.2%) with negative difference in 34 comparisons (29.3%). A positive significant correlation between PaCO2 and ETCO2 was recorded before (r = 0.617, p = 0.000) and at 15 minutes (r = 0.582, p = 0.001), with no significant correlation at 30 minutes (r = 0.142, p = 0.461), either after deflation (r = 0.108, p = 0.577). Bland-Altman plots showed agreement between ETCO2 and PaCO2 before inflation with mean PaCO2-ETCO2 difference 0.14 ± 5.6 mmHg (limits of 95% agreement -10.84-11.2, simple linear regression testing p-value 0.971), with no agreement at 15 minutes (0.51 ± 7.15, -13.5-14.5, p = 0.000), 30 minutes. (2.62 ± 7.83, -12.73-17.97, p = 0.000), or after deflation (1.81 ± 6.56, -10.93-14.55, p = 0.015). CONCLUSION: Usage of capnography as a trend monitor in pediatric laparoscopic surgeries may not be a reliable surrogate for PaCO2 levels. TRIAL REGISTRATION: Clinical Trials. gov (Identifier: NCT03361657).
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Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of UCP-2, UCP-3, GLUT-4, and PCSK9. Hypertension was associated with lower levels of UCP-2 and PCSK9 mRNA in the M. gastrocnemius, but increased expression of GLUT-1 and GLUT-4 in the M. soleus. Exercise down-regulated UCP-3 in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of UCP-2 in the M. soleus. Exercise increased the expression of GLUT-1 in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine IL-6 and that of GLUT-1 were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.
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This paper presents the studies of one and two component particles using a CO(2) laser for vaporization and VUV ionization in an ion trap mass spectrometer. The degree of fragmentation for a one component system was demonstrated to be a function of CO(2) laser energy. In a two component system, the degree of fragmentation was shown to be a function of the particle composition. This observation indicates that the analysis of mixed particles may be far more complicated than anticipated for a two step process with soft vaporization. In addition to showing that fragmentation is a function of CO(2) laser energy and particle composition, we also show that a key parameter that determines the extent of fragmentation is the energy absorbed by the particle during desorption. The ionization delay profile in a one component system is also shown to be strongly dependent on the vaporization energy. In a two component system, the delay profile is shown to strongly depend on the composition of the particle. The combined data suggest that the key parameter that governs the delay profile is the energy absorbed by the particle during desorption. This finding has implications for potential field measurements. Finally, for a two component system where the absorption crosssections are different, the change in the degree of fragmentation with particle composition resulted in a non-linear dependence of ion signal on composition. This makes any attempt at quantification difficult.
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Aerosoles/química , Espectrometría de Masas/instrumentación , Diseño de Equipo , Alcoholes Grasos/química , Iones/química , Rayos Láser , Espectrometría de Masas/métodos , Ácido Oléico/química , VolatilizaciónRESUMEN
INTRODUCTION: Cohorts from the electronic health record are often defined by the Current Procedural Terminology (CPT) codes. The error prevalence of CPT codes for patients receiving surgical treatment of metastatic disease of the femur has not been investigated, and the predictive value of coding ontologies to identify patients with metastatic disease of the femur has not been adequately discussed. METHODS: All surgical cases at a single academic tertiary institution from 2010 through 2015 involving prophylactic stabilization of the femur or fixation of a pathologic fracture of the femur were identified using the CPT and International Classification of Disease (ICD) codes. A detailed chart review was conducted to determine the procedure performed as documented in the surgical note and the patient diagnosis as documented in the pathology report, surgical note, and/or office visit notes. RESULTS: We identified 7 CPT code errors of 171 prophylactic operations (4.1%) and one error of 71 pathologic fracture fixation s(1.4%). Of the 164 prophylactic operations that were coded correctly, 87 (53.0%) had metastatic disease. Of the 70 pathologic operations that were coded correctly, 41 (58%) had metastatic disease. DISCUSSION: The error prevalence was low in both prophylactic stabilization and pathologic fixation groups (4.1% and 1%, respectively). The structured data (CPT and ICD-9 codes) had a positive predictive value for patients having metastatic disease of 53% for patients in the prophylactic stabilization group and 58% for patients in the pathologic fixation group. The CPT codes and ICD codes assessed in this analysis do provide a useful tool for defining a population in which a moderate proportion of individuals have metastatic disease in the femur at an academic medical center. However, verification is necessary.
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Current Procedural Terminology , Fracturas Espontáneas , Fémur , Fijación de Fractura , Humanos , Clasificación Internacional de EnfermedadesRESUMEN
Isolated adult rat ventricular cardiomyocytes (ARVC) adapt to the two-dimensional surface of culture dishes once they are isolated from the three-dimensional heart tissue. This process mimics aspects of cardiac adaptation to pressure overload and requires an initial breakdown of sarcomeric structures. The present study therefore aimed to identify key steps in this remodeling process. ARVC were cultured under serum-free or serum-supplemented conditions and their sizes and shapes were analyzed as well as apoptosis and the ability to disintegrate their sarcomeres. ARVC require serum-factors in order to adapt to cell culture conditions. More ARVC survived if they were able to breakdown their sarcomeres and mononucleated ARVC, which were smaller than binucleated ARVC, had a better chance to adapt. During the early phase of adaptation, proteasome subunit low molecular weight protein (LMP)-2 was induced. Inhibition of LMP-2 up-regulation by siRNA attenuated the process of successful adaptation. In vivo, LMP-2 was induced in the left ventricle of spontaneously hypertensive rats during the early phase of adaptation to pressure overload. In conclusion, the data suggest that breakdown of pre-existing sarcomeres is optimized by induction of LMP-2 and that it is required for cardiac remodeling processes, for example, occurring during pressure overload.