Child type 1 diabetes associated with mother vaginal bacteriome and mycobiome.

Mother vaginal microbes contribute to microbiome of vaginally delivered neonates. Child microbiome can be associated with autoimmune diseases, such as type 1 diabetes (T1D). We collected vaginal DNA samples from 25 mothers with a vaginally delivered child diagnosed with T1D and samples from 24 control mothers who had vaginally delivered a healthy child and analyzed bacteriome and mycobiome of the samples. The total DNA of the samples was extracted, and ribosomal DNA regions (16S for bacteria, ITS2 for fungi) were amplified, followed by next-generation sequencing and machine learning. We found that alpha-diversity of bacteriome was increased (P < 0.002), whereas alpha-diversity of mycobiome was decreased (P < 0.001) in mothers with a diabetic child compared to the control mothers. Beta-diversity analysis suggested differences in mycobiomes between the mother groups (P = 0.001). Random forest models were able to effectively predict diabetes and control status of unknown samples (bacteria: 0.86 AUC, fungi: 0.96 AUC). Our data indicate several fungal genera and bacterial metabolic pathways of mother vaginal microbiome to be associated with child T1D. We suggest that early onset of T1D in a child has a relationship with altered mother vaginal microbiome and that both bacteriome and mycobiome contribute to this shift.

Combining olfactory test and motion analysis sensors in Parkinson's disease preclinical diagnosis: a pilot study.

OBJECTIVES: Preclinical diagnosis of Parkinson's disease (PD) is nowadays a topic of interest as the neuropathological process could begin years before the appearance of motor symptoms. Several symptoms, among them hyposmia, could precede motor features in PD. In the preclinical phase of PD, a subclinical reduction in motor skills is highly likely. In this pilot study, we investigate a step-by-step method to achieve preclinical PD diagnosis. MATERIAL AND METHODS: We used the IOIT (Italian Olfactory Identification Test) to screen a population of healthy subjects. We identified 20 subjects with idiopathic hyposmia. Hyposmic subjects underwent an evaluation of motor skills, at baseline and after 1 year, using motion analysis sensors previously created by us. RESULTS: One subject showed significant worsening in motor measurements. In this subject, we further conducted a dopaminergic challenge test monitored with the same sensors and, finally, he underwent [123 I]-FP/CIT (DaTscan) SPECT brain imaging. The results show that he is probably affected by preclinical PD. CONCLUSIONS: Our pilot study suggests that the combined use of an olfactory test and motor sensors for motion analysis could be useful for a screening of healthy subjects to identify those at a high risk of developing PD.

Louis Appia (1818-98): military surgeon and member of the International Committee of the Red Cross.

From Appia's writings we compose a view on his contribution to international medical relief in warfare, to the establishment of the Red Cross and the Geneva Convention, and to surgical procedures on the battlefield. Much information comes from his work on the Battle of San Martino e Solferino in June 1859 on the subject of which he wrote seven letters. We report also on his role during the Garibaldinian Campaign in 1866 and his work in Europe as a member of the International Committee of the Red Cross (ICRC).

[The pacifism of Henry Dunant]. / Il pacifismo di Henry Dunant.

From various writings of the founder of the International Red Cross and above all from his late work L'avenir sanglant it is deduced as the Dunant anticipating and prophetically interpreting the curse of the war is an internationalist (for some aspects a romantic anarchist) and a convinced pacifist. We show therefore how much has been false and backbiters the defamations that followed to the attribution of the first Nobel prize for the peace.

Rewriting of the biography of Henry Dunant, the founder of the International Red Cross.

This paper presents quite a different version of the origins of the Red Cross from that officially recognised. On the basis of historical documents and statements of authors who are critical and attentive to the detail of the circumstances and events which gave rise to the Red Cross, it is possible to discern a surprising historical truth.

Lifestyle-related risk factors for Parkinson's disease: a population-based study.

OBJECTIVES: To investigate the association of major lifestyle-related risk factors with the prevalent cases of Parkinson's disease (PD) identified by the Italian Longitudinal Study on Aging. METHODS: A total of 5632 individuals randomly selected from the population registers of eight centers were screened for parkinsonism using both a questionnaire and a neurologic examination. Screened positives underwent a structured clinical work-up for the diagnosis of parkinsonism and parkinsonism subtypes. RESULTS: We identified 113 prevalent cases of PD. Age, male gender, and pesticide-use license were significantly related to PD. Heavy smoking was inversely related to PD. Age (OR = 1.1; 95% CI, 1.06-1.15) and pesticide-use license (OR = 3.7; 95% CI, 1.6-8.6) kept their significant correlation with the disease in the multivariate analysis to adjust for all the variables under investigation. Multivariate analyses were made for men and women separately: pesticide exposure was positively associated with PD only in men. CONCLUSIONS: Pesticide exposure might represent a candidate for environmental factors involved in PD.

Lipoprotein(a) and cognitive performances in an elderly white population: Cross-sectional and follow-up data.

BACKGROUND AND PURPOSE: Elevated lipoprotein(a) [Lp(a)] serum levels have been associated with an increased risk of vascular diseases, and preliminary observations suggest that they are a risk factor for vascular dementia. The relationship between Lp(a) levels and cognitive performances in the general population has never been investigated. Our aim was to evaluate the effect of elevated Lp(a) levels on cognitive functions in the elderly. METHODS: Cognitive performances were assessed by means of the Mini-Mental State Examination (MMSE), the Babcock Short Story, and the Matrix Test in a population sample of 435 white subjects aged 65 to 84 years who were evaluated at baseline and after 3 years. Lp(a) levels were determined by ELISA. RESULTS: No statistically significant difference was found in neuropsychological test scores between subjects with and without elevated Lp(a) levels, although subjects with elevated Lp(a) levels had slightly better cognitive performances. This difference reached a statistical significance level only in a subscore of the Matrix Test (number of correct responses) when adjusted for age, sex, education, smoking, and history of stroke. At follow-up, no statistically significant difference was found in cognitive performances between subjects with and without elevated Lp(a) serum levels in either univariate or multivariate analyses. Subjects with and without elevated Lp(a) showed a similar decline rate during follow-up. CONCLUSIONS: In this sample of elderly white subjects, elevated Lp(a) levels were not associated with poorer cognitive performances or with an increased rate of cognitive decline. Elevated Lp(a) levels do not appear to be a major determinant of cognitive impairment in the elderly.

Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project).

BACKGROUND AND PURPOSE: The role of atrial fibrillation (AF) as a determinant of stroke outcome is not well established. Studies focusing on this topic relied on relatively small samples of patients, scarcely representative of the older age groups. We aimed at evaluating clinical characteristics, care, and outcome of stroke associated with AF in a large European sample. METHODS: In a European Concerted Action involving 7 countries, 4462 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin scale). RESULTS: AF was present in 803 patients (18.0%). AF patients, compared with those without AF, were older, were more frequently female, and more often had experienced a previous myocardial infarction; they were less often diabetics, alcohol consumers, and smokers (all P:<0.001). At 3 months, 32.8% of the AF patients were dead compared with 19.9% of the non-AF patients (P:<0.001). With control for baseline variables, AF increased by almost 50% the probability of remaining disabled (multivariate odds ratio 1.43, 95% CI 1.13 to 1.80) or handicapped (multivariate odds ratio 1.51, 95% CI 1.13 to 2.02). Before stroke, only 8.4% of AF patients were on anticoagulants. The chance of being anticoagulated was reduced by 4% per year of increasing age. AF patients underwent CT scan and other diagnostic procedures less frequently and received less physiotherapy or occupational therapy. CONCLUSIONS: Stroke associated with AF has a poor prognosis in terms of death and function. Prevention and care of stroke with AF is a major challenge for European health systems.

Lipoprotein(a) serum levels and vascular diseases in an older Caucasian population cohort. Italian Longitudinal Study on Aging (ILSA).

OBJECTIVE: To investigate elevated lipoprotein(a) [Lp(a)] levels as a risk factor for stroke, myocardial infarction, angina, intermittent claudication, and combination of the above in a cohort of unselected older individuals. DESIGN: Population cohort from one of the eight centers participating in the Italian Longitudinal Study on Aging (ILSA). SETTING: General community. PARTICIPANTS: A subsample of 446 subjects (M/F: 231/ 215, mean age: 74.5 +/- 5.7 years) of the original, randomly selected, population cohort of 704 individuals, 65 to 84 years of age, free-living or institutionalized in the Impruneta Municipality, area of Florence, Italy. MEASUREMENTS: Conventional vascular risk factors and vascular diseases defined following a two-step procedure (screening phase and confirmation on positives) using standard and validated criteria. Lp(a) levels determined by an ELISA method. RESULTS: No association was observed between elevated Lp(a) levels alone and any of the examined vascular diseases (stroke, myocardial infarction, angina, and intermittent claudication). In contrast, examining the interactions between elevated Lp(a) and conventional vascular risk factors, when elevated Lp(a) was combined with a history of smoking, a marked increase in the risk of vascular diseases combined (odds ratio [OR]: 4.12; 95% confidence interval [CI]: 1.27-13.40) was observed, much higher than that expected based on the additive effect of smoking and elevated Lp(a) alone. CONCLUSIONS: With the cautions due to the cross-sectional design of the study and the limited statistical power, these results suggest a possible synergistic effect between elevated Lp(a) levels and other pro-atherogenic factors such as smoking on the risk of vascular diseases in older individuals.

Parkinson's disease and parkinsonism in a longitudinal study: two-fold higher incidence in men. ILSA Working Group. Italian Longitudinal Study on Aging.

OBJECTIVE: To determine the incidence of parkinsonism and PD in the Italian elderly, and to explore the relation with age and gender. METHODS: In eight Italian municipalities, a population-based, parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were directly contacted (screening and clinical examination). Cohort members who had died were studied using death certificates, clinical records, and information gathered from relatives and general practitioners. Parkinsonism diagnosis and subtyping were made according to specified diagnostic criteria. RESULTS: The cohort consisted of 4,341 individuals (65 to 84 years of age): 596 died before the examination, 2,863 (76.4% of the survivors) completed the screening procedure, and 882 refused to participate. The authors found 68 incident cases of parkinsonism: 42 PD (62%), 7 drug-induced parkinsonism (10%), 8 parkinsonism in dementia (12%), 8 vascular parkinsonism (12%), and 3 parkinsonism, unspecified (5.8%). Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 84 years, adjusted to the 1992 Italian population, was 529.7 (95% CI, 400.5 to 658.9) for parkinsonism, and 326.3 (95% CI, 224.1 to 427.5) for PD. Incidence rates for both parkinsonism and PD increased with age in both men and women; men had higher rates in every age group. Age-adjusted relative risk in men compared with women was 1.66 (95% CI, 1.02 to 2.70) for parkinsonism and 2.13 (95% CI, 1.11 to 4.11) for PD. CONCLUSIONS: Incidence of parkinsonism and PD increased with age, PD was the most common type of parkinsonism, and men had a risk of developing PD twice that of women.

Multisite inhibition of Pinus pinea isocitrate lyase by phosphate.

Our results show that the phosphate ion is a nonlinear competitive inhibitor of Pinus pinea isocitrate lyase. In addition, this compound induces a sigmoidal response of the enzyme, which usually exhibits standard Michaelis-Menten kinetics. This peculiar behavior of P. pinea isocitrate lyase could be explained by a dimer (two-site) model, in which phosphate binds cooperatively, but the affinity of the vacant site for substrate (the magnesium-isocitrate complex) remains the same. As a result, the interaction of phosphate with free enzyme produces an inhibitor-enzyme-inhibitor species that is of significant importance in determining reaction rate; a possible regulatory role of the glyoxylate cycle by inorganic phosphate is suggested. The mode of phosphate inhibition is consistent with both the mechanism for magnesium ion activation of P. pinea isocitrate lyase and its site heterogeneity. Our results explain the cooperative effects observed by some authors in kinetic studies of isocitrate lyase carried out in phosphate buffers and also account for the higher K(m) values determined by using such assay systems. Phosphate buffer should be avoided in performing isocitrate lyase kinetics.

Stroke in the very old : clinical presentation and determinants of 3-month functional outcome: A European perspective. European BIOMED Study of Stroke Care Group.

BACKGROUND AND PURPOSE: The oldest old represent the fastest-growing segment of the elderly population in developed countries. Knowledge of age-specific aspects of stroke is essential to establish diagnostic and therapeutic pathways and to set up prevention and rehabilitation programs. We sought to evaluate stroke features and functional outcome in patients aged >/=80 years compared with the younger age groups. METHODS: In a European Union Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month disability (Barthel Index) and handicap (Rankin Scale). RESULTS: Overall, 3141 patients (69.8%) were aged <80 years, and 1358 (30.2%) were aged >/=80 years. At baseline, female sex, prestroke institutionalization, and a worse prestroke Rankin score were significantly more frequent in the older patients, as were coma, paralysis, swallowing problems, and urinary incontinence in the acute phase (all P values <0.001). Brain imaging and other diagnostic tools were significantly less used in the older patients. Paralysis, swallowing problems, and incontinence during hospitalization independently predicted 3-month disability or handicap in both groups. For the older patients, prestroke institutionalization proved a further strong and independent determinant of 3-month disability (odds ratio, 2.33; 95% CI, 1.22 to 4.45) and handicap (odds ratio, 7.04; 95% CI, 1.62 to 30. 69). CONCLUSIONS: In the very old, both medical and sociodemographic factors may significantly influence stroke outcome, showing peculiar characteristics. Knowledge of these determinants may reduce the burden on health systems, improving quality of care.

Enzyme kinetic parameters are not altered by microgravity.

This paper deals with a microgravity experiment concerning the EMEC project (Effect of Microgravity on Enzymatic Catalysis), performed during the parabolic flight of the sounding rocket MASER 7, launched from the base of Esrange (Kiruna, Sweden) on May 3, 1996. The experiment consisted of performing, in a microgravity environment, a number of velocity measurements of an enzyme (isocitrate lyase) catalyzed reaction at different substrate concentrations, to calculate the kinetic parameters (Km and Vmax), which were compared with those obtained at standard gravity, with identical instrumentation. The experimental hardware, the EMEC module, expressly set up by Officine Galileo (Firenze, Italy) with the financial support of the European Space Agency, was a multichannel fibre-optics radiometer, equipped with an automatic injection system, that allowed to measure simultaneously the transmittance changes in 16 reaction cells. The results indicated that under the experimental conditions applied, microgravity has no appreciable effect on the enzyme kinetic constants.

Joseph Daquin, Piedmontese Savoyard physician, a "not well-known chiarugi".

We present a critical review of La philosophie de la folie, second edition, published in 1804. Joseph Daquin's thoughts and clinical activity in the psychiatric field are described. Daquin's ideas about various forms of madness and the different therapeutic, moral, physical treatments, his anatomical studies, successes and failures are presented. Several clinical cases are described. The author's view of the moon's influence on madness is described. Finally it is shown how very important was the human person and the moral treatment of madness for Daquin, in contrast with the current opinion at the end of 1700.

Incidence and determinants of poststroke dementia as defined by an informant interview method in a hospital-based stroke registry.

BACKGROUND AND PURPOSE: Inconsistent information about incidence and determinants of poststroke dementia might be related to patient attrition, partly because of nonapplicability of formal neuropsychological testing to a large proportion of patients registered in a definite setting. METHODS: Using a proxy-informant interview based on ICD-10 criteria, we determined dementia at stroke onset and 1 year after stroke in the 339 patients who survived, were available for follow-up, and were not demented at stroke onset of 635 patients entered over a 1-year period in a stroke registry taken at 2 community hospitals in Florence, Italy. RESULTS: Of the 339 patients, 57 (16.8%) proved to have poststroke dementia. These patients were older, more frequently female, and more often (multivariate odds ratio, 2.35; 95% CI, 1.21 to 4.58) had atrial fibrillation than those without dementia. Aphasia and the clinical features expressing the severity of the stroke event in the acute phase predicted poststroke dementia. CONCLUSIONS: In a hospital-based nonselected series of stroke survivors, despite the use of a method with low sensitivity for defining dementia, our study confirms that dementia is a frequent sequela of stroke and is mainly predicted by stroke severity. Certain determinants could be controlled in the prestroke phase, thus reducing its risk.

Gravitational effects on biological systems.

The possible effects of the earth's gravitational field on biological systems have been studied from a quantitative point of view, focusing the attention to a very simple system, a solution containing proteins, which biochemists might use in experiments. Gravity has been compared with other forces which are known to influence protein activity, including thermic agitation, weak electrostatic interactions, Van der Waals forces and viscous dissipation. Comparisons have been described in terms of the energy of the interaction per mole, referring to some physically simple cases and substances of biological interest. From this study it is evident that the earth's gravitational energy should be taken into account when considering the chemical behaviour of solutions containing substances that have high molecular weight, such as a typical protein, since its value is comparable to other weak interactions. Moreover, since solutions represent the basis of much more complex biological processes taking place inside cells, the influence of gravity should extend also to cellular biochemical behaviour, especially in presence of altered gravity, both in microgravity (such as on satellites orbiting around the earth), and in macrogravity (such as in a centrifugating biological system).