Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.

Effect of resin-modified glass-ionomer cement lining and composite layering technique on the adhesive interface of lateral wall.

UNLABELLED: Interface integrity can be maintained by setting the composite in a layering technique and using liners. OBJECTIVE: The aim of this in vitro study was to verify the effect of resin-modified glass-ionomer cement (RMGIC) lining and composite layering technique on the bond strength of the dentin/resin adhesive interface of lateral walls of occlusal restorations. MATERIAL AND METHODS: Occlusal cavities were prepared in 52 extracted sound human molars, randomly assigned into 4 groups: Group 2H (control) - no lining + two horizontal layers; Group 4O: no lining + four oblique layers; Group V-2H: RMGIC lining (Vitrebond) + two horizontal layers; and Group V-4O: RMGIC lining (Vitrebond) + four oblique layers. Resin composite (Filtek Z250, 3M ESPE) was placed after application of an adhesive system (Adper™ Single Bond 2, 3M ESPE) dyed with a fluorescent reagent (Rhodamine B) to allow confocal microscopy analysis. The teeth were stored in deionized water at 37oC for 24 hours before being sectioned into 0.8 mm slices. One slice of each tooth was randomly selected for Confocal Laser Scanning Microscopy (CLSM) analysis. The other slices were sectioned into 0.8 mm x 0.8 mm sticks to microtensile bond strength test (MPa). Data were analyzed by two-way ANOVA and Fisher's test. Results There was no statistical difference on bond strength among groups (p>0.05). CLSM analysis showed no significant statistical difference regarding the presence of gap at the interface dentin/resin among groups. CONCLUSIONS: RMGIC lining and composite layering techniques showed no effect on the microtensile bond strength and gap formation at the adhesive interface of lateral walls of high C-factor occlusal restorations.

Effect of resin-modified glass-ionomer cement lining and composite layering technique on the adhesive interface of lateral wall

Interface integrity can be maintained by setting the composite in a layering technique and using liners. Objective The aim of this in vitro study was to verify the effect of resin-modified glass-ionomer cement (RMGIC) lining and composite layering technique on the bond strength of the dentin/resin adhesive interface of lateral walls of occlusal restorations. Material and Methods Occlusal cavities were prepared in 52 extracted sound human molars, randomly assigned into 4 groups: Group 2H (control) – no lining + two horizontal layers; Group 4O: no lining + four oblique layers; Group V-2H: RMGIC lining (Vitrebond) + two horizontal layers; and Group V-4O: RMGIC lining (Vitrebond) + four oblique layers. Resin composite (Filtek Z250, 3M ESPE) was placed after application of an adhesive system (Adper™ Single Bond 2, 3M ESPE) dyed with a fluorescent reagent (Rhodamine B) to allow confocal microscopy analysis. The teeth were stored in deionized water at 37oC for 24 hours before being sectioned into 0.8 mm slices. One slice of each tooth was randomly selected for Confocal Laser Scanning Microscopy (CLSM) analysis. The other slices were sectioned into 0.8 mm x 0.8 mm sticks to microtensile bond strength test (MPa). Data were analyzed by two-way ANOVA and Fisher's test. Results There was no statistical difference on bond strength among groups (p>0.05). CLSM analysis showed no significant statistical difference regarding the presence of gap at the interface dentin/resin among groups. Conclusions RMGIC lining and composite layering techniques showed no effect on the microtensile bond strength and gap formation at the adhesive interface of lateral walls of high C-factor occlusal restorations. .

Necesidad de médicos especialistas en establecimientos de salud del sector salud / Need for medical specialists in health establishments in the health sector

La presente publicación describe dos estudios que se aproximan a la necesidad de médicos especialistas, uno de ellos para el ámbito público, y el otro para el ámbito de EsSalud y Fuerzas Armadas. Ámbos, vistos en conjunto, nos brindan una visión fundamental para poder diseñar estrategias de cierre de brechas que vayan más allá de los indicadores globales de densidad de recursos humanos, y que nos lleven al nivel de establecimiento, del momento de la verdad del contacto entre el paciente y el profesional que lo atiende(AU)

Necesidad de médicos especialistas en establecimientos de salud del sector salud / Need for medical specialists in health establishments in the health sector

La presente publicación describe dos estudios que se aproximan a la necesidad de médicos especialistas, uno de ellos para el ámbito público, y el otro para el ámbito de EsSalud y Fuerzas Armadas. Ámbos, vistos en conjunto, nos brindan una visión fundamental para poder diseñar estrategias de cierre de brechas que vayan más allá de los indicadores globales de densidad de recursos humanos, y que nos lleven al nivel de establecimiento, del momento de la verdad del contacto entre el paciente y el profesional que lo atiende.

Autopsy-confirmed Alzheimer's disease versus clinically diagnosed Alzheimer's disease in the Cache County Study on Memory and Aging: a comparison of quantitative MRI and neuropsychological findings.

Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically diagnosed using the same antemortem criteria will provide further evidence of the utility and accuracy of neuropsychological assessments at the time of diagnosis, as well as the efficacy of quantitative magnetic resonance imaging (qMRI) in demonstrating gross neuropathological changes associated with the disease. The Cache County Study of Aging provides a unique opportunity to determine how closely AD subjects with only the clinical diagnosis match similarly diagnosed AD subjects but with postmortem confirmation of the disease. qMRI volumes of various brain structures, as well as neuropsychological outcome measures from an expanded battery, were obtained in 31 autopsy-confirmed AD subjects and 45 clinically diagnosed AD subjects. Of the various qMRI variables examined, only total temporal lobe volume was different, where those with postmortem confirmation had reduced volume. No significant differences between the two groups were found with any of the neuropsychological outcome measures. These findings confirm the similarity in neuroimaging and neuropsychological assessment findings between those with just the clinical diagnosis of AD and those with an autopsy-confirmed diagnosis in the moderate-to-severe stage of the disease at the time of diagnosis.

Comparison of clinical and neuropathologic diagnoses of Alzheimer's disease in 3 epidemiologic samples.

BACKGROUND: Studies of dementia in populations avoid many of the selection biases in clinical samples but require special evaluation and diagnostic methods to obtain high participation rates. To address this issue, we developed a unique in-home dementia assessment. We assessed validity of these assessments using neuropathologic confirmation of the clinical diagnosis in 3 epidemiologic samples. METHODS: Subjects were 175 participants in 3 ongoing studies of dementia. Two were population based and identified dementia by cognitive screening. The third study sought volunteers via advertisements. Dementia evaluations were then conducted at the participants' residences by specially trained nurses and psychometricians. Evaluation results were interpreted, and preliminary diagnoses were assigned by a geropsychiatrist or neurologist and a psychologist. Final diagnoses were assigned by a consensus panel of neurologists, geropsychiatrists, and psychologists. We compared the clinical diagnoses with the gold-standard neuropathologic diagnoses for those participants who subsequently underwent autopsy. RESULTS: Among the demented, the sensitivity of a clinical diagnosis of probable or possible Alzheimer's disease (AD) was 93% across the 3 studies. The rate of overall diagnostic agreement was 81%. Measures of agreement did not differ meaningfully across varying levels of dementia severity. CONCLUSIONS: Rates of neuropathologic confirmation for clinical AD diagnoses in these studies were similar to those reported from clinic-based samples. These results support the validity of clinical diagnoses of AD from a structured in-home assessment of community dwelling and institutionalized individuals using relatively economical methods of dementia screening and assessment.

Population-based study of medical comorbidity in early dementia and "cognitive impairment, no dementia (CIND)": association with functional and cognitive impairment: The Cache County Study.

OBJECTIVE: Authors investigated medical comorbidity in persons with dementia and "Cognitive Impairment, No Dementia" (CIND). METHODS: The Cache County Study is an ongoing population-based study of the epidemiology of dementia, the risk factors for conversion from CIND to dementia, and the progression of dementia. As part of the study's first incidence wave, persons with dementia (N=149), CIND (N=225), or without cognitive impairment (N=321) were identified and studied. Participants received comprehensive clinical evaluations and were rated on the General Medical Health Rating (GMHR), a global measure of seriousness of medical comorbidity. Participants and informants also completed the Mini-Mental State Exam and provided self-report information about comorbid medical conditions and functioning in activities of daily living. RESULTS: There were few differences in number or type of comorbid medical conditions between persons with CIND and dementia, but persons with dementia were prescribed more medications. Stroke was more common in dementia participants, but other illnesses common in old age were not significantly different across cognitive groups. Medical comorbidity was more serious in both dementia and CIND, such that both groups were less likely to have "little to no" comorbidity. Seriousness of medical comorbidity was significantly associated with worse day-to-day functioning and cognition. CONCLUSIONS: Persons with CIND and dementia have more serious medical comorbidity than comparable persons without cognitive impairment. This comorbidity may play a role in the progression of CIND and dementia. Future studies should investigate the role of medical comorbidity and its treatment on dementia onset or progression, as well as the mechanisms mediating its neuropathologic effects.