The degeneration of locus coeruleus occurring during Alzheimer’s disease clinical progression: a neuroimaging follow-up investigation

\ua9 The Author(s) 2024.The noradrenergic nucleus Locus Coeruleus (LC) is precociously involved in Alzheimer’s Disease (AD) pathology, and its degeneration progresses during the course of the disease. Using Magnetic Resonance Imaging (MRI), researchers showed also in vivo in patients the disruption of LC, which can be observed both in Mild Cognitively Impaired individuals and AD demented patients. In this study, we report the results of a follow-up neuroradiological assessment, in which we evaluated the LC degeneration overtime in a group of cognitively impaired patients, submitted to MRI both at baseline and at the end of a 2.5-year follow-up. We found that a progressive LC disruption can be observed also in vivo, involving the entire nucleus and associated with clinical diagnosis. Our findings parallel neuropathological ones, which showed a continuous increase of neuronal death and volumetric atrophy within the LC with the progression of Braak’s stages for neurofibrillary pathology. This supports the reliability of MRI as a tool for exploring the integrity of the central noradrenergic system in neurodegenerative disorders

Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials

Objective To evaluate the benefits and harms of low dose aspirin in people with diabetes and no cardiovascular disease

Oral contraceptives and cancers of the breast and of the female genital tract. Interim results from a case-control study.

We analysed data from a case-control investigation conducted in Milan, Northern Italy, to evaluate the relation between the use of combination oral contraceptives and the risk of cancers of the breast, ovary, endometrium and cervix uteri. For the present analysis, 776 cases of histologically confirmed breast cancer, 406 of epithelial ovarian cancer and 170 of endometrial cancer aged under 60 were compared with a group of 1,282 subjects below age 60 admitted for a spectrum of acute conditions apparently unrelated to oral contraceptive use or to any of the known or potential risk factors for the diseases under study. Likewise, 225 cases of invasive cervical cancer were compared with 225 age-matched inpatient controls, and 202 cases of cervical intra-epithelial neoplasia with 202 outpatient controls identified in the same screening clinics. The age-adjusted relative risk estimates for ever vs. never use of combination oral contraceptives were 1.04 (95% confidence interval (CI) 0.73-1.37) for breast cancer, 0.68 (95% CI = 0.48-0.97) for epithelial ovarian cancer, 0.50 (95% CI = 0.23-1.12) for endometrial cancer, 1.49 (95% CI = 0.88-2.55) for cervical cancer and 0.77 (95% CI = 0.50-1.18) for cervical intra-epithelial neoplasia. The risk of ovarian cancer decreased and that of invasive cervical cancer increased with longer duration of use. Neither duration of oral contraceptive use nor time since first or last use significantly altered a user's risk of other neoplasms considered. Likewise, analysis of sub-groups of age, parity or other potentially important covariates did not show any important interaction, and allowance for them by means of logistic regression did not materially modify any of the results. These data confirm that combination oral contraceptives confer some protection against ovarian and endometrial cancers but may increase the risk of invasive cervical cancer if used for several years, and indicate that the past or current pattern of oral contraceptive use in Italy is unlikely materially to affect the risk of breast cancer

Non-medical risk factors as avoidable determinants of excess mortality in children with chronic kidney disease. A prospective cohort study in Nicaragua, a model low income country

Background: The widely recognized clinical and epidemiological relevance of the socioeconomic determinants of health-disease conditions is expected to be specifically critical in terms of chronic diseases in fragile populations in low-income countries. However, in the literature, there is a substantial gap between the attention directed towards the medical components of these problems and the actual adoption of strategies aimed at providing solutions for the associated socioeconomic determinants, especially in pediatric populations. We report a prospective outcome study on the independent contribution and reciprocal interaction of the medical and socioeconomic factors to the hard end-point of mortality in a cohort of children with chronic kidney disease in Nicaragua. Methods and Findings: Every child (n = 309) diagnosed with chronic kidney disease (CKD) and referred to the tertiary unit of Pediatric Nephrology in Managua (Nicaragua) from a network of nine hospitals serving 80% of the country's pediatric population was registered between January 2005 and December 2013. The three main socioeconomic determinants evaluated were family income, living conditions and the family's level of education. Further potential determinants of the outcomes included duration of exposure to disease, CKD stage at the first visit as suggested by the KDOQI guidelines in children, the time it took the patients to reach the reference centre and rural or urban context of life. Well-defined and systematically collected medical and socioeconomic data were available for 257 children over a mean follow-up period of 2.5\ub12.5 years. Mortality and lost to follow-up were considered as outcome endpoints both independently and in combination, because of the inevitably progressive nature of the disease. A high proportion (55%) of children presented in the advanced stages of CKD (CKD stage IV and V) at the first visit. At the end of follow-up, 145 (57%) of the 257 cohort children were alive, 47 (18%) were lost to follow-up and 65 (25%) had died. Cox regression analysis showed an independent contribution to mortality of CKD stage at diagnosis and of level of education, with overlapping HR values (HR and 95%CI: 2.66; 1.93-3.66 and 2.72; 1.71-4.33, respectively). Conclusions: The unfavourable socioeconomic and cultural background of the pediatric study cohort and the severity of kidney damage at diagnosis were the key determinants of the clinical risk conditions at baseline and of the mortality outcome. Long-term structural interventions on such backgrounds must be adopted to assure effectiveness of medical care and to assure an earlier diagnosis of CKD in these patients. The translation-extension of our results is currently underway with an agenda which includes: 1) better integration of chronic pediatric conditions into primary care strategies to promote prevention and early timely referral; 2) the consideration of socioeconomic conditions as a mandatory component of the packages of best-care; 3) the formulation and flexible adaptation of guidelines and educational programs, based on the information generated by a context-specific, epidemiological monitoring of needs and outcomes, guaranteed by an effective database

Prevalence of Defaecatory Disorders in Morbidly Obese Patients Before and After Bariatric Surgery

BACKGROUND: The prevalence of obesity is increasing worldwide and has lately reached epidemic proportions in western countries. Several epidemiological studies have consistently shown that both overweight and obesity are important risk factors for the development of various functional defaecatory disorders (DDs), including faecal incontinence and constipation. However, data on their prevalence as well as effectiveness of bariatric surgery on their correction are scant. The primary objective of this study was to estimate the effect of morbid obesity on DDs in a cohort of patients listed for bariatric surgery. We also evaluated preliminary results of the effects of sleeve gastrectomy on these disorders. PATIENTS AND METHODS: A questionnaire-based study was proposed to morbidly obese patients having bariatric surgery. Data included demographics, past medical, surgical and obstetrics histories, as well as obesity related co-morbidities. Wexner Constipation Score (WCS) and the Faecal Incontinence Severity Index (FISI) questionnaires were used to evaluate constipation and incontinence. For the purpose of this study, we considered clinically relevant a WCS ≥5 and a FISI score ≥10. The same questionnaires were completed at 3 and 6 months follow-up after surgery. RESULTS: A total of 139 patients accepted the study and 68 underwent sleeve gastrectomy and fully satisfied our inclusion criteria with a minimum follow-up of 6 months. Overall, mean body mass index (BMI) at listing was 47 ± 7 kg/m(2) (range 35-67 kg/m(2)). Mean WCS was 4.1 ± 4 (range 0-17), while mean FISI score (expressed as mean±standard deviation) was 9.5 ± 9 (range 0-38). Overall, 58.9% of the patients reported DDs according to the above-mentioned scores. Twenty-eight patients (20%) had WCS ≥5. Thirty-five patients (25%) had a FISI ≥10 while 19 patients (13.7%) reported combined abnormal scores. Overall, DDs were more evident with the increase of obesity grade: Mean BMI decreased significantly from 47 ± 7 to 36 ± 6 and to 29 ± 4 kg/m(2) respectively at 3 and 6 months after surgery (p < 0.0001). According to the BMI decrease, the mean WCS decreased from 3.7 ± 3 to 3.1 ± 4 and to 1.6 ± 3 respectively at 3 and 6 months (p = 0.02). Similarly, the FISI score decreased from 10 ± 8 to 3 ± 4 and to 1 ± 2 respectively at 3 and 6 months (p = 0.0001). CONCLUSIONS: Defaecatory disorders are common in morbidly obese patients. The risk of DDs increases with BMI. Bariatric surgery reduces DDs, mainly faecal incontinence, and these findings correlated with BMI reduction

Direct comparison of B-Type Natriuretic Peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data

Background: The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NTproBNP in patients with chronic and stable HF. Methods: We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves. Results: NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P 0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P 0.032) or hospitalization for HF (P 0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696. Conclusions: The natriuretic peptides BNP and NTproBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

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Evaluation of self-absorption of manganese emission lines in Laser Induced Breakdown Spectroscopy measurements

This paper is part of a more general study aimed to the determination of the best experimental procedures for reliable quantitative measurements of Fe-Mn alloys by LIBS. In this work, attention is pointed on the self-absorption processes, whose effect deeply influences the LIBS measurements, reflecting in non-linear calibration curves. The effect of self-absorption on the line intensity can be quantified by defining a self absorption coefficient, that measures the deviation of the line intensity from the linear extrapolation of the curve of growth in the optically thin regime. The authors demonstrated in a previous paper that self absorption coefficients could be calculated once the electron density of the plasma is known and the Stark coefficients of the lines are available. However, when the Stark coefficients of the lines of interest are not known, a different approach is needed. In this work a new method for evaluation of self absorption coefficients in LIBS measurements is presented, which does not require the knowledge of Stark coefficients. In order to understand the basic principles and setting out the theoretical tools that will be used for the analysis o f the alloys, a preliminary study was done on pure Mn; LIBS spectra were acquired in different experimental conditions, at different laser energies and different delays after the laser irradiation o f the sample. Moreover, collinear double pulse measurements were also performed. Analytical relations were derived and experimental procedures devised for evaluation o f the self absorption coefficients of several Mn lines, which are important for characterization and control of the experimental conditions in which the analysis is performed

Evaluation of self-absorption of manganese emission lines in laser induced breakdown spectroscopy measurements

This paper is part o f a more general study aimed to the determination o f the best experimental procedures for reliable quantitative measurements o f F e-M n alloys by LIBS. In this work, attention is pointed on the self-absorption processes, whose effect deeply influences the LIBS measurements, reflecting in non-linear calibration curves. The effect o f self-absorption on the line intensity can be quantified by defining a self absorption coefficient, that measures the deviation o f the line intensity from the linear extrapolation o f the curve o f growth in the optically thin regime. The authors demonstrated in a previous paper that self absorption coefficients could be calculated once the electron density o f the plasma is known and the Stark coefficients o f the lines are available. However, when the Stark coefficients o f the lines o f interest are not known, a different approach is needed. In this work a new method for evaluation o f self absorption coefficients in LIBS measurements is presented, which does not require the knowledge o f Stark coefficients. In order to understand the basic principles and setting out the theoretical tools that w ill be used for the analysis o f the alloys, a preliminary study was done on pure Mn; LIBS spectra were acquired in different experimental conditions, at different laser energies and different delays after the laser irradiation o f the sample. Moreover, collinear double pulse measurements were also performed. Analytical relations were derived and experimental procedures devised for evaluation o f the self absorption coefficients o f several Mn lines, which are important for characterization and control o f the experimental conditions in which the analysis is performed.Facultad de Ingenierí