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OBJECTIVE: To investigate the overall effect of whey protein supplementation on skeletal muscle mass in adults with type 2 diabetes mellitus (T2DM). METHODS: Systematic review of reports on corporal muscle mass from clinical trials that assessed the use of whey protein supplementation by means of validated techniques in patients with T2DM. PubMed, SCOPUS, Web of Science, LILACS, and SciELO databases were searched up to April 2022. Risk of bias was assessed by the Cochrane Collaboration Risk of Bias tool. We conducted a qualitative synthesis of information. RESULTS: Four studies (424 participants) that met the selection criteria were identified out of 1,787 records. Of these, 3 studies assessed the total muscle mass using dual-energy X-ray absorptiometry (DXA), and 1 reported changes to the transverse diameter of the vastus lateralis muscle with ultrasound imaging. In the intervention groups, DXA assessments demonstrated an increase in total muscle mass in 3 studies and in the appendicular muscle mass in 2. Changes to the proportion of muscle mass were not seen in the DXA studies and only a discrete difference was seen in the comparative groups studied by ultrasound imaging. CONCLUSION: Following the administration of whey protein supplementation in patients with T2DM, a partially positive effect was seen in skeletal muscle mass gain with a moderate certainty of evidence.
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Diabetes Mellitus Tipo 2 , Suplementos Dietéticos , Músculo Esquelético , Proteína de Suero de Leche , Adulto , Humanos , Absorciometría de Fotón , Administración Oral , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Músculo Esquelético/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteína de Suero de Leche/administración & dosificaciónAsunto(s)
Enfermedad de Crohn , Glomerulonefritis por IGA , Infliximab , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/efectos adversos , Infliximab/uso terapéutico , Infliximab/administración & dosificación , Glomerulonefritis por IGA/tratamiento farmacológico , Masculino , Adulto , Femenino , Factores de Tiempo , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/administración & dosificación , Persona de Mediana EdadRESUMEN
Introduction: Extensive research has explored the incorporation of humor in therapy, revealing its potential positive effects on clients' mental well-being and personal growth. However, limited research exists on how coaching could benefit from humor as an intervention and how its utilization impacts the interaction processes and outcomes for both the coachee and coach. Therefore, our research focuses on the use and effects of spontaneous humor within professional dialogues. This paper aims to extract insights from academic literature on humor in adjacent fields and apply these insights to the context of coaching. Methods: This paper offers implications for coaching theory and practice, alongside a proposed research agenda. The initial phase involves analyzing reviews on humor in professional contexts, and coaching. Secondly, following the PRISMA guidelines for review, we identified 13 empirical studies, which address the role of humor in counseling, psychotherapy, and mentoring. Results and discussion: Our findings suggest that humor serves as a valuable tool for establishing and deepening the working alliance, fostering adaptive coping mechanisms in clients, and enhancing the cognitive and behavioral process. Moreover, humor is shown to be advantageous for professionals in navigating challenging client relationships. These findings hold significance for the realm of coaching practice as well. In light of these insights, we propose the integration of humor use in education toolkits for coaching professionals.
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BACKGROUND: In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. METHODS: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020. RESULTS: A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004). CONCLUSIONS: Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.
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Huésped Inmunocomprometido , Tuberculosis , Humanos , Estudios de Casos y Controles , Niño , Masculino , Femenino , Adolescente , Europa (Continente)/epidemiología , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Preescolar , Lactante , Prueba de Tuberculina , Antituberculosos/uso terapéuticoRESUMEN
Genetic studies indicate that breast cancer can be divided into several basic molecular groups. One of these groups, termed IntClust-2, is characterized by amplification of a small portion of chromosome 11 and has a median survival of only five years. Several cancer-relevant genes occupy this portion of chromosome 11, and it is thought that overexpression of a combination of driver genes in this region is responsible for the poor outcome of women in this group. In this study we used a gene editing method to knock out, one by one, each of 198 genes that are located within the amplified region of chromosome 11 and determined how much each of these genes contributed to the survival of breast cancer cells. In addition to well-known drivers such as CCND1 and PAK1 , we identified two different genes ( SERPINH1 and P4HA3 ), that encode proteins involved in collagen synthesis and organization. Using both in vitro and in vivo functional analyses, we determined that P4HA3 and/or SERPINH1 provide a critical driver function on IntClust-2 basic processes, such as viability, proliferation, and migration. Inhibiting these enzymes via genetic or pharmacologic means reduced collagen synthesis and impeded oncogenic signaling transduction in cell culture models, and a small-molecule inhibitor of P4HA3 was effective in treating 11q13 tumor growth in an animal model. As collagen has a well-known association with tissue stiffness and aggressive forms of breast cancer, we believe that the two genes we identified provide an opportunity for a new therapeutic strategy in IntClust-2 breast cancers.
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Calcium carbonate (CaCO3) is abundant on Earth, is a major component of marine biominerals and thus of sedimentary and metamorphic rocks and it plays a major role in the global carbon cycle by storing atmospheric CO2 into solid biominerals. Six crystalline polymorphs of CaCO3 are known-3 anhydrous: calcite, aragonite, vaterite, and 3 hydrated: ikaite (CaCO3·6H2O), monohydrocalcite (CaCO3·1H2O, MHC), and calcium carbonate hemihydrate (CaCO3·½H2O, CCHH). CCHH was recently discovered and characterized, but exclusively as a synthetic material, not as a naturally occurring mineral. Here, analyzing 200 million spectra with Myriad Mapping (MM) of nanoscale mineral phases, we find CCHH and MHC, along with amorphous precursors, on freshly deposited coral skeleton and nacre surfaces, but not on sea urchin spines. Thus, biomineralization pathways are more complex and diverse than previously understood, opening new questions on isotopes and climate. Crystalline precursors are more accessible than amorphous ones to other spectroscopies and diffraction, in natural and bio-inspired materials.
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Antozoos , Nácar , Animales , Carbonato de Calcio/química , Minerales/química , CristalizaciónRESUMEN
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
RAC1P29S is the third most prevalent hotspot mutation in sun-exposed melanoma. RAC1 alterations in cancer are correlated with poor prognosis, resistance to standard chemotherapy, and insensitivity to targeted inhibitors. Although RAC1P29S mutations in melanoma and RAC1 alterations in several other cancers are increasingly evident, the RAC1-driven biological mechanisms contributing to tumorigenesis remain unclear. Lack of rigorous signaling analysis has prevented identification of alternative therapeutic targets for RAC1P29S-harboring melanomas. To investigate the RAC1P29S-driven effect on downstream molecular signaling pathways, we generated an inducible RAC1P29S expression melanocytic cell line and performed RNA-sequencing (RNA-seq) coupled with multiplexed kinase inhibitor beads and mass spectrometry (MIBs/MS) to establish enriched pathways from the genomic to proteomic level. Our proteogenomic analysis identified CDK9 as a potential new and specific target in RAC1P29S-mutant melanoma cells. In vitro, CDK9 inhibition impeded the proliferation of in RAC1P29S-mutant melanoma cells and increased surface expression of PD-L1 and MHC Class I proteins. In vivo, combining CDK9 inhibition with anti-PD-1 immune checkpoint blockade significantly inhibited tumor growth only in melanomas that expressed the RAC1P29S mutation. Collectively, these results establish CDK9 as a novel target in RAC1-driven melanoma that can further sensitize the tumor to anti-PD-1 immunotherapy.
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Melanoma , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Proteómica , Melanocitos , Carcinogénesis , Línea Celular , Quinasa 9 Dependiente de la Ciclina , Proteína de Unión al GTP rac1/genéticaRESUMEN
Background and objectives: Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue. The combination of trabectedin plus low-dose radiation therapy (T-XRT) demonstrated a response rate of 60% in phase I/II trial, while real-life data achieved 32.5% ORR, probably due to a more relaxed timing between treatments. These results were obtained in progressing and advanced STS. In this study, the merged databases (trial plus real life) have been analyzed, with a special focus on leiomyosarcoma patients. Design and methods: As responses were seen in a wide range of sarcoma histologies (11), this study planned to analyze whether leiomyosarcoma, the largest subtype with 26 cases (30.6%) in this series, exhibited a better clinical outcome with this therapeutic strategy. In addition, four advanced and progressing leiomyosarcoma patients, all with extraordinarily long progression-free survival of over 18 months, were collected. Results: A total of 847 cycles of trabectedin were administered to 85 patients, with the median number of cycles per patient being 7 (1-45+). A trend toward a longer progression-free survival (PFS) was observed in leiomyosarcoma patients with median PFS (mPFS) of 9.9 months [95% confidence interval (CI): 1.1-18.7] versus 5.6 months (95% CI: 3.2-7.9) for the remaining histologies, p = 0.25. When leiomyosarcoma and liposarcoma were grouped, this difference reached statistical significance, probably due to the special sensitivity of myxoid liposarcoma. The mPFS for L-sarcomas was 12.7 months (95% CI: 7-18.5) versus 4.3 months (95% CI: 3.3-5.3) for the remaining histologies, p = 0.001. Cases with long-lasting disease control are detected among leiomyosarcoma patients. Conclusion: Even when extraordinarily long-lasting responses do exist among leiomyosarcoma patients treated with T-XR, we were unable to demonstrate a significant difference favoring leiomyosarcoma patients in clinical outcomes.
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Humanos , Femenino , Persona de Mediana Edad , Nalgas/lesiones , Trastornos Migrañosos/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Quistes/cirugía , Echinococcus granulosus/microbiología , Equinococosis/diagnóstico , Enfermedades Transmisibles , Examen Físico , Microbiología , Pacientes InternosRESUMEN
Un hombre de 57 años acudió a urgencias con astenia, mareo y tos con expectoración purulenta. Ingresó a cargo del Servicio de Neumología, y se objetivó en la imagen de tomografía axial computarizada un espacio aéreo grande en el lóbulo superior derecho. Esta lesión se atribuyó a un absceso pulmonar y se aisló Streptomyces albus en las muestras respiratorias. El género Streptomyces a menudo causa infecciones de la piel y tejidos blandos. Bacteriemia, neumonía y otros cuadros son raros. En nuestro caso, el paciente presentó un absceso pulmonar de gran tamaño, a pesar de los escasos síntomas descritos. La presentación del caso es atípica, dado que S. albus no suele causar abscesos pulmonares de manera aislada. (AU)
A 57-year-old man presented with asthenia, dizziness, and cough with purulent expectoration. He was admitted to the Pulmonology Unit, and a big air space in the right upper lobe was observed in computed tomography, which was characterized as a lung abscess, and Streptomyces albus was isolated. Streptomyces usually causes superficial skin and soft tissue infections. Bacteriemia, pneumonia, and other diseases are rarely seen. Our case is presented as a big lung abscess; nonetheless, our patient was paucisymptomatic. This case presentation describes the unusual phenomenon of a lung abscess caused by S. albus solely. (AU)
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Humanos , Masculino , Persona de Mediana Edad , Absceso Pulmonar/diagnóstico por imagen , Streptomyces , Tomografía Computarizada por Rayos XRESUMEN
Antecedentes: Los pacientes en hemodiálisis padecen, debido a su diagnóstico y tratamiento, mayores niveles de ansiedad y depresión que la población general. El objetivo de esta investigación es conocer el impacto emocional generado por la COVID-19 en pacientes hemodializados. Método: Estudio transversal analítico en una muestra total de 88 pacientes mayores de 18 años que reciben hemodiálisis entre abril de 2021 y marzo de 2022. Se recogen variables sociodemográficas y clínicas incluyendo aquellas relacionadas con COVID-19. A todos los pacientes se les administran las escalas HADS y Kessler-10. Resultados: La puntuación media de la escala HADS-A fue de 5,3 (±3,732), de la HADS-D de 5,45 (±4,052) y de la Kessler-10 de 20,11(±7,499). Se observaron diferencias significativas entre aislados y no aislados en las escalas clínicas HADS-A (p=,002) y HADS-D (p=,005). Igualmente, aquellos pacientes con antecedentes psicopatológicos fueron significativamente más jóvenes (p=,014) y con una mayor puntuación en las escalas HADS-D (p=,016) y Kessler-10 (p=,035) que aquellos sin antecedentes. Conclusiones: No hubo asociación entre infección por COVID-19 y la clínica ansioso-depresiva en pacientes hemodializados. El aislamiento, en estos pacientes, no se asocia a la aparición de clínica psicopatológica, mientras que el hecho de haber presentado antecedentes psicopatológicos previos se asocia a su desarrollo.(AU)
Background: Hemodialysis patients suffer, due to their diagnosis and treatment, higher levels of anxiety and depression than the general population. The aim of this research is to know the emotional impact generated by COVID-19 in hemodialysis patients. Method: Analytical cross-sectional study in a total sample of 88 patients over 18 years of age receiving hemodialysis between April 2021 and March 2022. Sociodemographic and clinical variables including those related to COVID-19 are collected. All patients were administered the HADS and Kessler-10 scales. Results: The mean score of the HADS-A scale was 5.3(±3.732) of the HADS-D 5.45 (±4.052) and of the Kessler-10 20.11(±7.499). Significant differences were observed between isolated and non-isolated patients in the clinical scales HADS-A (p=.002) and HADS-D (p=.005). Likewise, those patients with a psychopathological history were significantly younger (p=.014) and scored higher on the HADS-D (p=.016) and Kessler-10 (p=.035) scales than those without a history. Conclusions: There was no association between COVID-19 infection and anxious-depressive symptoms in hemodialyzed patients. Isolation, in these patients, was not associated with the appearance of psychopathological symptoms, while the fact of having a previous history of psychopathology was associated with their development.(AU)
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Cambio Social , Impacto Psicosocial , /psicología , Trastornos Mentales , Diálisis Renal/psicología , Estudios Transversales , Salud Mental , /complicaciones , /epidemiología , Psiquiatría , Depresión , Ansiedad , Pacientes/psicologíaRESUMEN
Mixed matrix membranes (MMMs) provide the opportunity to test new porous materials in challenging applications. A series of low-cost porous organic polymer (POPs) networks, possessing tunable porosity and high CO2 uptake, has been obtained by aromatic electrophilic substitution reactions of biphenyl, 9,10-dihydro-9,10-dimethyl-9,10-ethanoanthracene (DMDHA), triptycene and 1,3,5-triphenylbenzene (135TPB) with dimethoxymethane (DMM). These materials have been characterized by FTIR, 13C NMR, WAXD, TGA, SEM, and CO2 uptake. Finally, different loadings of these POPs have been introduced into Matrimid, Pebax, and chitosan:polyvinyl alcohol blends as polymeric matrices to prepare MMMs. The CO2/CH4 separation performance of these MMMs has been evaluated by single and mixed gas permeation experiments at 4 bar and room temperature. The effect of the porosity of the porous fillers on the membrane separation behavior and the compatibility between them and the different polymer matrices on membrane design and fabrication has been studied by Maxwell model equations as a function of the gas permeability of the pure polymers, porosity, and loading of the fillers in the MMMs. Although the gas transport properties showed an increasing deviation from ideal Maxwell equation prediction with increasing porosity of the POP fillers and increasing hydrophilicity of the polymer matrices, the behavior of biopolymer-based CS:PVA MMMs approached that of Pebax-based MMMs, giving scope to not only new filler materials but also sustainable polymer choices to find a place in membrane technology.
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A new set of microporous organic polymers (POPs) containing diphosphine derivatives synthesized by knitting via Friedel-Crafts has been attained. These amorphous three-dimensional materials have been prepared by utilizing diphosphines, 1,3,5-triphenylbenzene, and biphenyl as nucleophile aromatic groups, dimethoxymethane as the electrophilic linker, and FeCl3 as a promoting catalyst. These polymer networks display moderate thermal stability and high microporosity, boasting BET surface areas above 760 m2/g. They are capable of coordinating with palladium acetate, using the phosphine derivative as an anchoring center, and have proven to be highly efficient catalysts in Suzuki-Miyaura coupling reactions involving bromo- and chloroarenes under environmentally friendly (using water and ethanol as solvents) and aerobic conditions. These supported catalysts have achieved excellent turnover numbers (TON) and turnover frequencies (TOF), while maintaining good recyclability without significant loss of activity or Pd leaching after five consecutive reaction cycles.
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BACKGROUND: The scientific literature was reviewed to determine the state of the art regarding innovative educational practices that employ mobile health applications with the aim of establishing healthy habits in the adolescent population, following a strategy based on spiral curriculum. METHODS: The search was conducted in the WOS, Scopus and PubMed databases, discarding any articles that were not published in English, Spanish or French. The search was limited to studies performed in the last 6 years, that is, from 1 January 2017 to 18 March 2023. RESULTS: From the initial sample of 132 articles selected, the final sample included 9 articles that met the eligibility criteria after a more exhaustive analysis. This systematic review identified one application (11.11%) with topics about sex and reproductive health, two applications (22.22%) that tackled mental health, six applications (66.66%) with topics about nutrition, three applications (33.33%) that contemplate physical activity, and two applications (22.22%) with aspects related to the prevention of harmful habits. The results show a positive relationship between the use of mobile health applications used as innovative didactic resources and the establishment of healthy habits in the adolescent population. CONCLUSIONS: Digital devices have been incorporated to the lives of humans as fundamental tools for their daily living. Specifically, adolescents are especially attracted to mobile phones. If this resource is used in this population to improve health, it is possible to attain very satisfactory objectives. The results of this review indicate that these devices can be used as a didactic resource in the promotion of health by implementing healthy habits at early ages, thereby contributing to the prevention of chronic diseases in future adulthood.
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Teléfono Celular , Aplicaciones Móviles , Adolescente , Humanos , Adulto , Escolaridad , Curriculum , HábitosRESUMEN
Introduction: The ζ subunit is a potent inhibitor of the F1FO-ATPase of Paracoccus denitrificans (PdF1FO-ATPase) and related α-proteobacteria different from the other two canonical inhibitors of bacterial (ε) and mitochondrial (IF1) F1FO-ATPases. ζ mimics mitochondrial IF1 in its inhibitory N-terminus, blocking the PdF1FO-ATPase activity as a unidirectional pawl-ratchet and allowing the PdF1FO-ATP synthase turnover. ζ is essential for the respiratory growth of P. denitrificans, as we showed by a Δζ knockout. Given the vital role of ζ in the physiology of P. denitrificans, here, we assessed the evolution of ζ across the α-proteobacteria class. Methods: Through bioinformatic, biochemical, molecular biology, functional, and structural analyses of several ζ subunits, we confirmed the conservation of the inhibitory N-terminus of ζ and its divergence toward its C-terminus. We reconstituted homologously or heterologously the recombinant ζ subunits from several α-proteobacteria into the respective F-ATPases, including free-living photosynthetic, facultative symbiont, and intracellular facultative or obligate parasitic α-proteobacteria. Results and discussion: The results show that ζ evolved, preserving its inhibitory function in free-living α-proteobacteria exposed to broad environmental changes that could compromise the cellular ATP pools. However, the ζ inhibitory function was diminished or lost in some symbiotic α-proteobacteria where ζ is non-essential given the possible exchange of nutrients and ATP from hosts. Accordingly, the ζ gene is absent in some strictly parasitic pathogenic Rickettsiales, which may obtain ATP from the parasitized hosts. We also resolved the NMR structure of the ζ subunit of Sinorhizobium meliloti (Sm-ζ) and compared it with its structure modeled in AlphaFold. We found a transition from a compact ordered non-inhibitory conformation into an extended α-helical inhibitory N-terminus conformation, thus explaining why the Sm-ζ cannot exert homologous inhibition. However, it is still able to inhibit the PdF1FO-ATPase heterologously. Together with the loss of the inhibitory function of α-proteobacterial ε, the data confirm that the primary inhibitory function of the α-proteobacterial F1FO-ATPase was transferred from ε to ζ and that ζ, ε, and IF1 evolved by convergent evolution. Some key evolutionary implications on the endosymbiotic origin of mitochondria, as most likely derived from α-proteobacteria, are also discussed.
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OBJECTIVES: Neck recurrence of papillary thyroid cancer (PTC) is frequently detected after initial surgery. The management of these lesions may include rescue surgery (RS) or minimally invasive techniques in selected patients, but comparative studies evaluating the effectiveness and safety of these techniques are lacking. In this paper, we compared ultrasound-guided ethanol ablation (EA) in selected patients to RS in a matched cohort. METHODS: We retrospectively compared 41 patients and 41 matched PTC patients without known distant metastases, who underwent ultrasound-guided EA or RS (matched reference group), who had 63 and 75 thyroid bed and/or lymph node confirmed PTC recurrences during a median follow-up of 72.8 and 89.6 months, respectively. The primary outcome was time until structural recurrence, compared using Kaplan-Meier survival curves. The secondary outcomes included time until biochemical recurrence, plasma thyroglobulin (Tg) levels, American Thyroid Association (ATA) response-to-therapy categories by the last available observation, and treatment-derived complications in each group. RESULTS: No significant differences were found between the EA and RS groups for time until structural recurrence (log-rank test, P=0.94). The time until biochemical recurrence was also similar (P=0.51); and the plasma Tg concentration reduction and proportions of patients in the ATA reclassification categories were also similar. A significantly higher proportion of patients in the RS group presented treatment-derived complications (29.27% vs. 9.75%, P<0.05). CONCLUSION: In this retrospective analysis, the treatment of PTC neck recurrence with EA in selected patients was comparable to RS in a matched reference group for the long-term risk of structural or biochemical relapse, but with a lower risk of treatment-derived complications. These. RESULTS: support the effectiveness and safety of this minimally invasive technique in the management of selected patients with recurrent PTC.
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RAC1P29S is the third most prevalent hotspot mutation in sun-exposed melanoma. RAC1 alterations in cancer are correlated with poor prognosis, resistance to standard chemotherapy, and insensitivity to targeted inhibitors. Although RAC1P29S mutations in melanoma and RAC1 alterations in several other cancers are increasingly evident, the RAC1-driven biological mechanisms contributing to tumorigenesis remain unclear. Lack of rigorous signaling analysis has prevented identification of alternative therapeutic targets for RAC1P29S-harboring melanomas. To investigate the RAC1P29S-driven effect on downstream molecular signaling pathways, we generated an inducible RAC1P29S expression melanocytic cell line and performed RNA-sequencing (RNA-seq) coupled with multiplexed kinase inhibitor beads and mass spectrometry (MIBs/MS) to establish enriched pathways from the genomic to proteomic level. Our proteogenomic analysis identified CDK9 as a potential new and specific target in RAC1P29S-mutant melanoma cells. In vitro, CDK9 inhibition impeded the proliferation of in RAC1P29S-mutant melanoma cells and increased surface expression of PD-L1 and MHC Class I proteins. In vivo, combining CDK9 inhibition with anti-PD-1 immune checkpoint blockade significantly inhibited tumor growth only in melanomas that expressed the RAC1P29S mutation. Collectively, these results establish CDK9 as a novel target in RAC1-driven melanoma that can further sensitize the tumor to anti-PD-1 immunotherapy.
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Men with alcohol and/or other drug use problems (ADUPs) court-mandated to attend intervention programs for intimate partner violence (IPV) perpetrators have been identified as a high-risk, highly resistant group of IPV perpetrators, as they present lower treatment adherence and higher dropout and recidivism rates. Previous research suggests that IPV perpetrators with ADUPs may require tailored interventions to address their specific risk factors. The present systematic review was conducted using PRISMA guidelines to identify the specific risk factors in men with and without ADUPs on entry to court-mandated perpetrator programs. The following databases were searched from inception to November 2021: Web of Science, PsycINFO, and Scopus. There was a screening of 3,995 records, and 29 quantitative studies were included in the review. Risk factors present in males court-mandated to perpetrator programs were grouped into four categories: sociodemographic risk factors, personality disorders and psychological adjustment, social-relational risk factors, and risk factors related to attitudes towards women. Results indicated that the main risk factors in IPV perpetrators with ADUPs, compared to those without, were higher clinical symptomatology (e.g., anger and impulsivity), personality disorders, poorer executive functions, having experienced more stressful life events, higher exposure to childhood trauma, lower intimate social support, and higher responsibility attributed to the offenders' personal context. These results contribute to a deeper understanding of the complex phenomenon of IPV and ADUPs, and could help to inform key targets for perpetrator programs that may improve the well-being of their (ex)partners and increase the effectiveness of intervention programs for IPV perpetrators.
Los hombres que presentan consumo problemático de alcohol y otras drogas (CPAD) y que acuden por mandato judicial a programas de intervención para agresores de pareja constituyen un grupo de agresores resistentes a la intervención y de alto riesgo, ya que presentan una menor adherencia al tratamiento y una mayor frecuencia de abandono y reincidencia. La investigación previa indica que los participantes con CPAD pueden necesitar intervenciones adaptadas en las que se traten los factores de riesgo específicos. La presente revisión sistemática se ha llevado a cabo siguiendo las directrices PRISMA con el fin de conocer los factores de riesgo específicos en participantes con y sin CPAD al inicio de la intervención. La búsqueda bibliográfica se realizó en las siguientes bases de datos hasta noviembre del 2021: Web of Science, PsycINFO y Scopus. Se examinaron 3,995 estudios, incluyéndose 29 estudios cuantitativos en la revisión. Los factores de riesgo de los hombres que acudieron por mandato judicial a intervenciones con agresores de pareja se agrupan en cuatro categorías: sociodemográficos, trastornos de la personalidad y ajuste psicológico, sociorrelacionales y relativos a las actitudes hacia la mujer. Los resultados indican que los principales factores de riesgo en agresores de pareja con CPAD, comparados con aquellos que no tienen este problema, se caracterizan por una mayor sintomatología clínica (e.g., ira e impulsividad), trastornos de la personalidad, deficiencias en las funciones ejecutivas, mayor exposición a hechos vitales estresantes, trauma en la infancia, menor apoyo social íntimo y mayor tendencia a atribuir la responsabilidad de la conducta violenta a su contexto personal. Estos resultados contribuyen a una comprensión más profunda de la compleja relación entre la violencia de pareja y el CPAD y de los objetivos clave de los programas para agresores, con el fin de aumentar el bienestar de la (ex)pareja y la eficacia de dichos programas.