Perinatal outcome in anti-NMDAr encephalitis during pregnancy-a systematic review with individual patients' data analysis.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. METHODS: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. RESULTS: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. CONCLUSIONS: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment.

Neutrophil, lymphocyte count, and neutrophil to lymphocyte ratio predict multimorbidity and mortality-results from the Baltimore Longitudinal Study on Aging follow-up study.

Immunosenescence is the age-related changes in the immune system, namely, progressively higher levels of circulating inflammatory markers, characteristics changes of circulating immune subset cells and altered immune function. The neutrophil to lymphocyte ratio (NL ratio) has been identified as a prognostic indicator for neoplastic disease progression, in predicting chronic degenerative diseases, and as a potential indirect marker of healthy aging. This study aims to examine the longitudinal association of neutrophil, lymphocyte absolute count, and their ratio with longitudinal risk for multimorbidity and mortality. The Baltimore Longitudinal Study of Aging (BLSA) is an open observational cohort study of community-dwelling volunteers that are followed every 1-4 years depending on their age. The sample considered in the study consists of 1769 participants (5090 follow-ups) with completed data for physical examination, health history assessment, and donated a blood sample. The NL ratio increased with age and was associated with a higher risk of mortality, while a lower NL ratio was inversely correlated with multimorbidity. Neutrophils increased with aging and an increase in their absolute number predicted mortality risk. However, the absolute number of lymphocytes was associated with age only in a cross-sectional analysis. In conclusion, this study supports the importance of the NL ratio and absolute neutrophil count as markers of aging health status, and as significant predictors of all-cause mortality and multimorbidity in aging individuals. It remains to be demonstrated whether interventions contrasting these trends in circulating cells may result in improved health outcomes.

Beyond Inflammaging: The Impact of Immune System Aging on Age-Related Muscle Decline, Results From the InCHIANTI Study.

Aging is characterized by chronic low-level inflammation and is associated with geriatric syndromes such as sarcopenia and frailty. Our aim was to evaluate the longitudinal variation of muscle area, muscle quality, and muscle strength, relative to the variation of leukocyte-derived markers, and to assess the presence of a pathway of associations among derived leukocyte ratios, and the components of muscle health. The InCHIANTI is a longitudinal cohort study of aging that began in 1998 with follow-up visits every 3 years. Out of the 1 453 participants enrolled at baseline, this study includes 1 179 participants with complete data. Muscle strength was assessed by hand grip strength test, whereas muscle density and fat area were considered as indirect markers of muscle quality, derived from peripheral quantitative computed tomography of the calf. Muscle area was associated with neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, and body mass index (BMI). Muscle density variation over time was inversely associated with age, comorbidities, and BMI, while being positively associated with monocyte-to-lymphocyte ratio (ML-ratio) and male gender. Fat area was inversely associated with age, interleukine-6 (IL-6), male gender, and NL-ratio, while being positively associated with ML-ratio, comorbidities, and BMI. Handgrip strength decreased with age, IL-6 levels, comorbidities, and NL-ratio, but increased with ML-ratio, being male, and having a higher BMI. In a path-analysis model, ML-ratio positively correlates with muscle mass, density, and strength, while NL-ratio only correlates inversely with muscle mass and density. NL-ratio and ML-ratio are associated with aging and may be implicated in age-related mechanisms that affect body composition and muscle strength. These ratios may represent a link between aging of the immune system and decline of muscle health with aging. However, further studies are needed to identify their usefulness for early detection of sarcopenia, myosteatosis, and frailty in the older adult.

Urinary and Daily Assumption of Polyphenols and Hip-Fracture Risk: Results from the InCHIANTI Study.

A high polyphenol intake has been associated with higher bone-mineral density. In contrast, we recently demonstrated that the urinary levels of these micronutrients were associated with the long-term accelerated deterioration of the bone. To expand on the health consequences of these findings, we assessed the association between urinary level and dietary intake of polyphenols and the 9-year risk of hip fractures in the InCHIANTI study cohort. The InCHIANTI study enrolled representative samples from two towns in Tuscany, Italy. Baseline data were collected in 1998 and at follow-up visits in 2001, 2004, and 2007. Of the 1453 participants enrolled at baseline, we included 817 participants in this study who were 65 years or older at baseline, donated a 24 hour urine sample, and underwent a quantitative computerized tomography (pQCT) of the tibia. Fracture events were ascertained by self-report over 9 years of follow-up. Thirty-six hip fractures were reported over the 9-year follow-up. The participants who developed a hip fracture were slightly older, more frequently women, had a higher dietary intake of polyphenols, had higher 24-hour urinary polyphenols excretion, and had a lower fat area, muscle density, and cortical volumetric Bone Mineral Density (vBMD) in the pQCT of the tibia. In logistic regression analyses, the baseline urinary excretion of total polyphenols, expressed in mg as a gallic acid equivalent, was associated with a higher risk of developing a hip fracture. Dietary intake of polyphenols was not associated with a differential risk of fracture. In light of our findings, the recommendation of an increase in dietary polyphenols for osteoporosis prevention should be considered with caution.

Choroidal Changes in Blood Flow in Patients with Intermediate AMD after Oral Dietary Supplement Based on Astaxanthin, Bromelain, Vitamin D3, Folic Acid, Lutein, and Antioxidants.

Background and Objectives: The aim of this study was to investigate the impact of oral administration of the combination of astaxanthin (AXT), lutein, folic acid, vitamin D3, and bromelain with antioxidants on choroidal blood flow in patients with age-related intermediate macular degeneration (AMD). Materials and Methods: Patients affected by intermediate AMD and treated with daily oral nutritional supplement with AXT, bromelain, vitamin D3, folic acid, lutein, and antioxidants for a period of at least 6 months were included in this retrospective study. A control group homogenous for age and sex was also included in the analysis. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA) evaluation. Outcome measures were choroidal thickness (CHT) and choriocapillary vessel density (CCVD) after six months of AXT assumption. Results: CCVD values showed statistically significant difference between cases and controls at baseline (p < 0.001) and in the cases during follow-up (p < 0.001). The CHT measurements showed statistically significant difference between cases and controls (p = 0.002) and in the cases during follow-up (p < 0.001). Conclusions: The combined use of structural OCT and OCTA allows for a detailed analysis in vivo of perfusion parameters of the choriocapillaris and choroid and evaluation of changes of choroidal blood flow after oral nutritional supplements that affect blood flow velocity.

Efficacy of Ultrasound-Guided Percutaneous Lavage and Biocompatible Electrical Neurostimulation, in Calcific Rotator Cuff Tendinopathy and Shoulder Pain, A Prospective Pilot Study.

Calcific tendinopathy of the shoulder (CTS) is the most common cause of shoulder pain. Conservative treatment is considered as the first therapeutic choice for CTS. The main objective of this study was to assess the effect of US-guided needling (UGN) compared to UGN plus Biocompatible Electrical Neurostimulation (BEN) in the treatment of the CTS. Pilot, prospective, non-interventional, monocentric, and observational study of patients treated for calcific rotator cuff tendinopathy and shoulder pain. Patients' selection, enrollment and interventions were conducted at the Chiparo Physical Medicine and Rehabilitation outpatient facility. Forty adult patients (aged 40−60 years) with a diagnosis of CTS in the acute and colliquative phase were recruited and enrolled into the study. Participants were assessed for self-perceived pain through the Numerical Rating Scale (NRS), and for functional limitation through the Shoulder Pain and Disability Index score (SPADI) at baseline (T0), after 15 days (T1), and after 40 days (T2). As a possible confounding factor between the two treatments' response, the dimension of the tendon calcification was also assessed by US-examination. Through the study, both groups improved their perceived functional performance of the arm (p-value < 0.001). AT T1, the SPADI score decreased by half in both groups, and the improvement remained stable at T2. A multiplicative effect (Time × Treatment) was demonstrated (p-value < 0.001). An improvement in the NRS score was measured at T1, and it remained stable at T2, a multiplicative effect was also reported (p-value < 0.001). The main results of this pilot study provide evidence that UGN plus BEN increases functional performance and reduces shoulder pain in individuals with CTS. Moreover, the tendon calcification dimension at the baseline and the percentage of drainage of the lesion were associated with a functional performance recovery and pain reduction detected after intervention.

Effects of activity tracker-based counselling and live-web exercise on breast cancer survivors' sleep and waking time during Italy's COVID-19 lockdown.

The aim of the study was to compare the effects of weekly personal feedback, based on objectively measured physical activity, on daily sleep in breast cancer survivors (BCS) with those of an intervention that also included online supervised physical exercise sessions (OSPES). BCS benefiting from both personal feedback and OSPES (n = 24), from pre-lockdown (T0) to the first month (T1) of the national lockdown, experienced an increase in both total (p ≤ 0.001) and restorative (p ≤ 0.001) sleep time, inverting their trend from the first month of lockdown to its end (total sleeping time T1 vs. T2 0.01 ≤ p < .001, T1 vs. T3 p ≤ 0.001; restorative sleeping time T1 vs. T2 0.05 ≤ p < .01, T1 vs. T3 p ≤ 0.001). Supportive technology, together with the reception of weekly tailored advice and OSPES seems to improve both quality and quantity of sleep.

Baker's Cyst with Knee Osteoarthritis: Clinical and Therapeutic Implications.

OBJECTIVE: Several symptoms are common to knee osteoarthritis and Baker's cyst. To what extent each condition contributes to the patient's discomfort is still a matter of debate. The aim of the present study was twofold: first, to compare the burden of symptoms in patients with isolated knee osteoarthritis and patients with knee osteoarthritis associated with Baker's cyst; second, to assess the outcomes after conservative treatments. SUBJECT AND METHODS: Patients suffering from monolateral idiopathic knee osteoarthritis were enrolled. Demographic, anthropometric and clinical data (KOOS scale) were collected. Ultrasound evaluation was performed according to standard protocols. On the basis of the clinical presentation different therapeutic options were used (fluid withdrawal, hyaluronic acid and/or steroids injections). RESULTS: One-hundred and thirty patients were included in the study (97 with isolated knee osteoarthritis, 33 with knee osteoarthritis and Baker's cyst). In basal conditions, lower scores in KOOS sub-scales were observed in patients with knee osteoarthritis associated with Baker's cyst and in patients with effusion compared with patients without effusion. At 3 months after therapy significant higher scores were observed in both groups. At 6 months the scores were unchanged in the patients without Baker's cyst, but worsened in those with Baker's cyst. CONCLUSIONS: The study shows that Baker's cysts associated with knee osteoarthritis contribute to the burden of symptoms. The conservative treatment of both conditions allows significant improvements, but in the medium term (6 months) the efficacy of the therapy declines in patients with knee osteoarthritis associated with Baker's cyst.

Effects of Activity Tracker-Based Counselling and Live-Web Exercise on Breast Cancer Survivors during Italy COVID-19 Lockdown.

BACKGROUND: To prevent and fight the increase of daily sedentary time and to promote and stimulate the positive effects of physical activity and exercise on health, both traditional interventions and new strategies are important for breast cancer survivors (BCS). The research goal was to compare the effects of weekly personal feedback, based on objectively measured physical activity, on the trends of both daily sedentary time and on the physical activity of BCS (E- group) with those of an intervention also including online supervised physical exercise sessions (E+ group), during the Italy COVID-19 lockdown. METHODS: The Italian COVID-19 emergency allowed the possibility to also observe the effects of social and personal limitations. A total of 51 BCS were studied over an 18-week period and had an objective registration of day-to-day sedentary time, physical activity, and sleep. Both subsamples received weekly or fortnight personal feedback. Data were analysed considering four key periods, according to the COVID-19 emergency steps. RESULTS: Statistical analysis showed an additive effect for sedentary time and a multiplicative effect both for light-to vigorous and light-intensity physical activities. The E- group had a high overall sedentary time and a different trend of light-to vigorous and light-intensity physical activities, with a reduction from the 1st to the 2nd periods (national and personal restrictions), showing a significant rise just at the end of the national restrictions. CONCLUSIONS: The use of an activity tracker and its accompanying app, with the reception of weekly tailored advice and supervised online physical exercise sessions, can elicit proper physical activity recomposition in BCS in the COVID-19 era.

Levetiracetam Prophylaxis Therapy for Brain Tumor-Related Epilepsy (BTRE) Is Associated With a Higher Psychiatric Burden.

Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis. Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up. Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed. Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM.

Walking training and cortisol to DHEA-S ratio in postmenopause: An intervention study.

The literature indicates that the plasma cortisol-to-dehydroepiandrosterone-sulfate (DHEA-S) ratio is a marker of health status after menopause, when a decline in both estrogen and DHEA-S and an increase in cortisol occur. An increase in the cortisol-to-DHEA-S ratio has been positively correlated with metabolic syndrome, all-cause mortality, cancer, and other diseases. The aim of this study was to investigate the effects of a walking program on the plasma cortisol-to-DHEA-S ratio in postmenopausal women. Fifty-one postmenopausal women participated in a 13-week supervised walking program, in the metropolitan area of Pescara (Italy), from June to September 2013. Participants were evaluated in April-May and September-October of the same year. The linear mixed model showed that the variation of the log10Cortisol-to-log10DHEA-S ratio was associated with the volume of exercise (p = .03). Participants having lower adherence to the walking program did not have a significantly modified log10Cortisol or log10DHEA-S, while those having the highest adherence had a significant reduction in log10Cortisol (p = .016) and a nearly significant increase in log10DHEA-S (p = .084). Walking training appeared to reduce the plasma log10Cortisol-to-log10DHEA-S ratio, although a minimum level of training was necessary to achieve this significant reduction.

Central serous chorioretinopathy treated with navigated retinal laser photocoagulation: visual acuity and retinal sensitivity.

BACKGROUND AND OBJECTIVE: To evaluate the effect of navigated retinal laser photocoagulation on visual acuity (VA) and retinal sensitivity in eyes with acute central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Prospective, noncomparative, interventional case series of 30 eyes of 29 patients with acute CSC were treated using navigated photocoagulation. Patients were monitored for 180 days. RESULTS: Mean VA improved from 0.3 ± 0.1 to 0.1 ± 0.1 logMAR (P < .001). Mean retinal sensitivity within central 8° and 4° improved from 9.4 ± 4.7 dB to 14.9 ± 3.6 dB and from 9.0 ± 5.6 dB to 14.6 ± 4.2 dB respectively (P < .001). In all cases, a decrease in mean central retinal thickness of -50.6 ± 2.9 µm (P < .001) and in mean subretinal fluid thickness of -52.0 ± 3.3 µm (P < .001) was observed during follow-up. CONCLUSION: Navigated retinal laser photocoagulation demonstrated safety and accuracy for the treatment of acute CSC. VA and retinal sensitivity evaluations showed a significant improvement associated with resolution of the subretinal fluid during follow-up.

Increased variance in germline allele-specific expression of APC associates with colorectal cancer.

BACKGROUND & AIMS: Germline variations in allele-specific expression (ASE) are associated with highly penetrant familial cancers, but their role in common sporadic cancers is unclear. ASE of adenomatous polyposis coli (APC) is associated with pathogenesis of familial adenomatous polyposis. We investigated whether moderate variations in ASE of APC contribute to common forms of colorectal cancer (CRC). METHODS: Denaturing high-performance liquid chromatography was used to analyze germline ASE of APC in blood samples from patients with CRC (cases, n = 53) and controls (n = 68). Means, medians, and variances of ASE were compared. Variants in the APC gene region also were analyzed. RESULTS: The distribution of ASE differed significantly between groups; cases had significantly larger amounts of variance than controls (P = .0004). Risk for CRC increased proportionally with the degree of deviation from the mean. The odds ratio for individuals with levels of ASE that deviated more than 1 standard deviation from the mean was 3.97 (95% confidence interval, 1.71-9.24; P = .001); for those with levels greater than 1.645 standard deviations, the odds ratio was 13.46 (95% confidence interval, 1.76-609.40; P = .005). Sequence analysis revealed that a patient with a high level of ASE who did not have a family history of CRC carried a nonsense mutation in APC (p.Arg216X). Genotype analysis of APC associated multiple single-nucleotide polymorphisms with ASE values and/or variance among cases, but not controls. Cis variants, therefore, might account for some of the variance in ASE of APC. CONCLUSIONS: Patients with CRC have a larger variance in germline levels of ASE in APC than controls; large distances from the mean ASE were associated with risk for common forms of CRC.

Antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients.

BACKGROUND: Hypertension is more prevalent among HIV-infected individuals than in the general population and contributes to increased cardiovascular risk. The angiotensin II receptor blocker telmisartan is also a partial peroxisome proliferator activated receptor-γ agonist with documented effects on glucose and lipid homeostasis. The aim of this study was to evaluate the antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients. METHODS: A total of 18 HIV-positive men treated with antiretroviral therapy and recently diagnosed with hypertension were administered 80 mg telmisartan daily. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), viroimmunological and metabolic parameters, insulin resistance, C-reactive protein, microalbuminuria, cystatin C and plasma levels of interleukin-18 and endothelin-1 were measured at baseline (T0), 1 month (T1), 3 months (T3) and 6 months (T6). RESULTS: Treatment with telmisartan not only decreased SBP and DBP levels, but also improved insulin resistance and microalbuminuria by T1. Levels of triglycerides significantly decreased and high-density lipoprotein cholesterol increased at T1, whereas total and low-density lipoprotein cholesterol levels were statistically reduced at T3 and T6. Cystatin C and endothelin-1 showed a significant reduction at T1, whereas interleukin-18 decreased at both T3 and T6. CONCLUSIONS: Telmisartan was effective in reducing blood pressure and improving lipid metabolism and renal function. Reduction of endothelin-1 might be related to an endothelial protective effect. On the basis of these findings, and because of properties unrelated to blood pressure lowering, telmisartan might be the first choice antihypertensive drug for the treatment of HIV-positive patients.

Cystatin C, adipokines and cardiovascular risk in HIV infected patients.

OBJECTIVES: To value the role of leptin, adiponectin and cystatin C in HIV infected patients treated with combined antiretroviral therapy (cART) subdivided for cardiovascular risk (CVR). METHODS: 56 HIV+ cART treated patients were screened by Framingham score and subdivided in 2 groups: A) 15 with "high" CVR (>10%) and B) 41 with "low" CVR (<10%). Viro-immunological parameters, triglycerides, total cholesterol, HDL and LDL cholesterol, blood pressure, microalbuminuria, fasting glucose, insulinemia, HOMA-IR, CRP, cystatin C, IL-18, IL-6, leptin, adiponectin, antropometric parameters and total abdominal tissue (TAT), subcutaneous (SAT) and visceral abdominal tissue (VAT) were measured. RESULTS: Group A showed statistically higher levels of parameters of glucose and lipid metabolism, cystatin-C, microalbuminuria, blood pressure and BMI. Moreover levels of IL-6, IL-18 and leptin were statistically higher in group A, whereas adiponectin was statistically increased in group B. Data showed a positive correlation between VAT, leptin levels (r=0.37, p=0.005) and IL-18 (r=0.32, p=0.01), and a negative correlation between VAT and adiponectin (r=-0.30, p=0.02). Finally group A showed statistically higher levels of cystatin C and there was a positive correlation between CVR and cystatin C (r=0.39, p=0.003). CONCLUSIONS: The main results of this study are that HIV positive subjects cART treated with "high" CVR have increased plasma levels of leptin, IL-6, IL-18 and cystatin C and hypoadiponectinemia. Moreover, the positive correlation between CVR and cystatin C found in this study for the first time in HIV positive patients, indicates that cystatin C could serve as early marker of enhanced CVR in the HIV-infected population.

Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study.

BACKGROUND: Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength. METHODS: In a representative sample of 716 men and women aged >or=65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up. RESULTS: In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones. CONCLUSIONS: Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging.

Nonfluorescent denaturing HPLC-based primer-extension method for allele-specific expression: application to analysis of mismatch repair genes.

BACKGROUND: Altered germline expression of genes may represent a powerful marker of genetic or epigenetic predisposition to cancer or other diseases. METHODS: We developed and validated a method of nonfluorescent primer extension that uses a single dideoxynucleotide and denaturing HPLC (DHPLC) to analyze the relative allele expression. We devised 5 independent assays for measuring allele-specific expression (ASE) to exploit different markers of mismatch repair genes MLH1 [mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)] and MSH2 [mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)]. We initially confirmed method reproducibility with genomic DNA (gDNA) from individuals heterozygous for a frequent single-nucleotide polymorphism in the MLH1 gene. After this preliminary validation with gDNA, we confirmed assay reproducibility with cDNA templates from control individuals. Relative allele expression was estimated by comparing the heights of the peaks corresponding to the 2 alleles. Results obtained with gDNA templates were used to normalize cDNA results. RESULTS: With these DHPLC-based primer-extension assays, we detected and confirmed a 5-fold imbalance in MLH1 allele expression in a mutation-negative patient with hereditary nonpolyposis colorectal cancer and in another patient with a modest degree of imbalance in MLH1 expression. Among control individuals, the relative expression of MLH1 alleles displayed a narrow range of variation. CONCLUSIONS: Independent DHPLC-based primer-extension assays for measuring and confirming ASE can be developed for different sequence variants of interest. This DHPLC application provides a cost-effective method for detecting ASE in cases for which conventional screening fails to detect pathogenic mutations in candidate genes and may be applicable for confirming ASE revealed by other methods, such as those used for transcriptome-wide analyses. .

Effects of vascular risk factors on balance assessed by computerized posturography in the elderly.

AIMS: The purpose of this study was to evaluate the effects of vascular risk factors, isolated or in association, on balance, as assessed by posturographic platform. METHODS: One hundred and seven elderly subjects (mean age 73.8+/-5.8), with no cognitive impairment (MMSE>24), able to perform self-care activities and to walk independently for at least 400 meters, free from major diseases. Subjective complaints were assessed by means of the Sickness Impact Profile Questionnaire. The following cardiovascular risk factors were considered: hypercholesterolemia, smoking, hypertension, glucose intolerance, and obesity. Balance tests were performed in three standardized positions (side-by-side, semi-tandem, tandem) on a vertical force platform, from which center of foot pressure positions and displacements were recorded. RESULTS: A large percentage of enrolled subjects (35.5%) complained of unsteadiness, dizziness or vertigo, but only a few (24=22.4%) reported at least one fall in the 6 months before enrolment in the study. Among the cardiovascular risk factors taken into account, only glucose intolerance and, to a lesser extent, obesity, were associated with worse performance in stabilometric tests, independent of age and sex. Subjects with 3 or more risk factors, compared with those with 2 or less showed worse performance in medio-lateral sway (p=0.001), track length (p=0.05) and elliptical area (p=0.005), in tandem position. CONCLUSIONS: The cumulative presence of cardiovascular risk factors may contribute to impairment of balance in the elderly. This effect may be due to subclinical damage of that part of the nervous system controlling balance.

Uric acid and dementia in community-dwelling older persons.

BACKGROUND: The biological action of uric acid (UA) in humans is controversial. UA is considered an antioxidant compound, but preclinical evidence suggests a proinflammatory action. Epidemiological studies found that hyperuricemia is associated with conditions leading to dementia. Our aim is to investigate the relationship between UA levels and dementia in older persons. METHODS: Cross-sectional study performed in 1,016 community-dwelling older persons participating in the InCHIANTI study. Participants underwent determination of circulating UA levels and neuropsychological evaluation. A multivariate logistic regression model was used to estimate the probability of participants belonging to the highest and middle UA tertile to be affected by dementia compared to those in the lowest tertile. RESULTS: Demented persons had higher UA levels (p = 0.001) and the prevalence of persons affected by dementia increased across UA tertiles (p < 0.0001). Independent of several confounders, persons belonging to the highest UA tertile had a threefold (OR = 3.32; 95% CI: 1.06-10.42) higher probability to suffer from a dementia syndrome while those in the middle UA tertile tended to have a higher probability of being demented compared to those in the lowest tertile. CONCLUSION: In a population-based sample, high circulating UA levels are associated with an increased likelihood to be affected by a dementia syndrome.

Low total plasma carotenoids are independent predictors of mortality among older persons: the InCHIANTI study.

BACKGROUND: Plasma carotenoids are considered a valid biological marker for fruit and vegetable dietary intake. Recent studies show that low carotenoid levels are associated with a high risk of inflammation, cancer, and cardiovascular disease. AIM OF THE STUDY: To determine whether low plasma carotenoids are associated with increased mortality among older adults. METHODS: Longitudinal study among 1,043 adults, 65 years and older, in the InCHIANTI study, a population-based cohort of adults living in the community in the Tuscany region, Italy. RESULTS: Mean total carotenoid concentration was 1.80 micromol/l. During eight years of follow-up, 310 (29.7%) of participants died. Eight-year survival was lower in the lowest compared with the highest tertile of total serum carotenoids (P < 0.0001 by Mantel-Haenszel chi-square). In a multivariate Cox proportional hazards model adjusted for age, education, smoking, body mass index, energy intake, and chronic diseases, adults in the highest tertile of plasma carotenoids at enrollment had lower mortality compared to those in the lowest tertile (Hazards Ratio obtained by considering carotenoids level as an ordinal variable 0.81, 95%; CI 0.65-0.99; P for trend = 0.046). CONCLUSIONS: Low plasma carotenoids are an independent risk factor for mortality among older adults living in the community.