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Background Palliative care for people with dementia is often sub-optimal. This is partly because of the challenging nature of dementia itself, and partly because of system failings that are particularly salient in primary care and community services. There is a need to systematize palliative care for people with dementia, to clarify where changes in practice could be made. To develop a model of palliative care for people with dementia that captures commonalities and differences across Europe, a technology development approach was adopted, using mixed methods including 1) critical synthesis of the research literature and policy documents, 2) interviews with national experts in policy, service organisation, service delivery, patient and carer interests, and research in palliative care, and 3) nominal groups of researchers tasked with synthesising data and modelling palliative care. Discussion A generic model of palliative care, into which quality indicators can be embedded. The proposed model includes features deemed important for the systematisation of palliative care for people with dementia. These are: the division of labour amongst practitioners of different disciplines; the structure and function of care planning; the management of rising risk and increasing complexity; boundaries between disease-modifying treatment and palliative care and between palliative and end-of-life care; and the process of bereavement. Summary The co-design approach to developing a generic model of palliative care for people with dementia has placed the person needing palliative care within a landscape of services and professional disciplines. This model will be explored further in the intervention phase of the IMPACT project. © 2013 Iliffe et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The economic trend in our country, as in other countries, now requires us to pay more attention to the social and economic aspects of health. Therefore, it is important to evaluate the diagnostic pathway and the socioeconomic aspects of pathologies. The Italian CTS Study Group performed a wide multicentre and multidimensional study (through a patient-, physician- and neurophysiologically oriented evaluation) on 461 idiopathic CTS patients to evaluate the clinical-neurophysiological picture and the diagnostic pathway. The whole population and the differences between the populations enrolled in the neurophysiological centres of the northern, central and southern parts of Italy were analysed. This study provided new and interesting information. As concerns the whole population, we observed different diagnostic pathways in relation to the level of schooling. As concerns the comparison of the populations, the southern centres have a population of CTS patients with higher frequency of hand stress and more severe nerve impairment.

On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life.

Owing to their intrinsic amplifying effect together with their temporal resolution, field-effect transistors (FETs) are gaining momentum for the detection of different biomolecules at ultralow concentration levels such as, for example, neurotransmitters, particularly if the concentration level of the analyte is below the detection limit of commonly used electrochemical sensing methods. We demonstrate the fabrication of a spearhead reduced graphene oxide (rGO)-based FET. The fabrication of the rGO-based FET by means of an electrochemical pulse deposition technique enables a controllable process including both the deposition and reduction of the deposited graphene oxide between two carbon nanoelectrodes to form the channel of the rGO-based FET. While using double-barrel carbon nanoelectrodes, the as-produced FETs offer new possibilities in terms of their applicability in very small volumes as well as the option of being positioned close to the desired measurement region. The fabrication process was evaluated and optimized to obtain rGO-based FETs with high performance. The as-fabricated devices were evaluated in terms of sensitivity and selectivity towards dopamine. The tested devices not only showed high sensitivity towards dopamine with a linear response ranging from 1 nM to 1μM, but also maintained a similar sensing performance in the presence of 500 μM ascorbic acid.

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic.

Objective: In developmental hip dysplasia (DDH) patients, the chronic dislocation of the femoral head with respect to the true acetabulum determines muscle contracture and atrophy, particularly of the abductor muscles, and leads to secondary osteoarthritis (OA) with severe motor dysfunction, pain and disability. The correct positioning when a total hip replacement (THR) is performed is fundamental to the recovery of gait function. Also, inadequate rehabilitation of the abductor muscles for pelvic stabilisation can be responsible for residual dysfunction. Consensus on a programme for abductor muscle strengthening in these patients is not currently available. The aim of this study was to evaluate the effectiveness of a specific program of exercises for strengthening the abductor muscles in these patients. Methods: A multicentre, prospective, randomised clinical trial was carried out in an outpatient rehabilitation setting on 103 patients given THR for DDH through a minimally-invasive anterolateral approach. Patients were randomly divided into a Study Group, including 46 patients, and a Control Group, including 57 patients. All patients underwent standard early postoperative rehabilitation. In addition, the Study Group were given an extra 2-week rehabilitation once full weight-bearing on the operated limb was allowed, aimed at strengthening the abductor muscles. All patients were evaluated preoperatively, and at about 3 and 6 months postoperatively. Clinical measures (lower limb-length differences, hip range of motion, abductor muscle strength), and functional measures (WOMAC, HHS, 10mt WT, SF-12) were taken. Results: Hip range of motion and functional outcome measures showed a progressive improvement at follow ups in both groups, significantly higher in the Study Group. In particular, abductor strength at 6 months post-op improved by 92.5% with respect to 35.7% in the Control Group. Conclusion: In addition to standard rehabilitation, a rehabilitation programme for strengthening the gluteal muscles in DDH patients who underwent THR determined an increase in muscle strength that improved functional performance and patient satisfaction.

Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.

Objectives: The aim was to report indications, technical aspects, and outcomes of a multicentre experience of late open conversions (LOCs) after endovascular abdominal aneurysm repair (EVAR), in order to identify risk factors which may influence early morbidity and mortality rates, and long term survival. Methods: Ten vascular centres retrospectively reviewed all patients requiring LOC (≥30 days from initial EVAR, undergoing total or partial endograft explantation) from 1996 to 2017. Baseline characteristics, endograft data, indications, procedural details, post-operative outcomes, and follow up data were reviewed and analysed. Results: Included patients totalled 232 (90.1% males, mean age 74.3 ± 7.9 years). The number of LOC per year significantly increased during the study period, reaching 22 in 2017 (correlation r = 0.867, p

Background The objective of this study is to report an 18-year single-center experience in the surgical and endovascular treatment of arterial complications due to self-injection in drug abuser patients. Methods This retrospective single-center study was conducted analyzing a prospectively collected database including all endovascular or surgical procedures performed from January 2007 to December 2019 for any arterial complication due to self-injection in drug abuser patient. Collected data were patient demographic and comorbidity, site and type of arterial lesion (pseudoaneurysm [PA], arteriovenous fistula [AVF]), signs of systemic or local infection, and procedural data (endovascular/surgical treatment). End points were rate of postoperative complications, reintervention rate, limb salvage, and patients’ early and long-term survival. Results In 11 patients (median age 36 years, range 27–47; male 73%), 13 arterial lesions were treated: 10 (77%) PA, 2 (15%) PA associated with AVF, and 1 (8%) isolated AVF. Arterial lesion involved common femoral artery in 5 (38%), superficial femoral artery in 4 (31%), profunda femoral artery in 1 (8%), brachial artery in 2 (15%), and subclavian artery in 1 (8%). Signs of infections were present in 9 of the 13 cases (69%). The treatment was surgical in 11 (85%) cases: 7 interposition graft (6 great saphenous vein, 1 arterial cryopreserved homograft), 2 direct reconstruction, 1 patch plasty with pericardium bovine patch, and 1 arterial ligation. Endovascular treatment was performed in 2 cases: 1 noninfected PA of the superficial femoral artery, and 1 55-mm PA of the postvertebral segment of the right subclavian artery with clinical sign of hemodynamic instability. At 1 month, postoperative complication rate was 8% (one lower limb claudication after superficial femoral artery ligation). Reintervention rate was 8% (interposition graft rupture for repeated self-injections). Limb salvage and patient survival were both 100%. Median follow-up was 5 years (range 1 month to 11.3 years); surgical group: median 8.2 years (range 2 months to 11.3 years); endovascular group: median 3.5 months (range 1–6). During follow-up, neither complications nor reinterventions occurred, and limb salvage was 100% for both groups. At 2, 4, and 6 years, overall estimated patient survival was 91%, 81%, and 81%, respectively, with no procedure-related death. Conclusions After surgical or endovascular management of arterial lesions due to self-injection in drug abuser patients, complications occur mainly in the postoperative period. During follow-up, the surgical procedures have low rate of complications, reinterventions, and procedure-related mortality, whereas for the endovascular treatment the mid-term outcomes remain unknown.

Background Insufficient evidence is available to recommend a particular strategy for the treatment of type 1a endoleaks (T1aELs) after endovascular abdominal aneurysm repair (EVAR). The aim of this study was to report outcomes of the different treatment modalities proposed for persistent and late-occurring T1aEL after EVAR. Methods A systematic review of the literature (database searched: PubMed, Web of Science, Scopus, Cochrane Library) was undertaken until August 2018. Studies about treatment of T1aEL after EVAR (excluding intraoperative treatments during the first EVAR) presenting a series of 5 or more patients with extractable outcome data (at least intraoperative and/or early results) were included. Meta-analyses of proportions were performed using a random-effects model. Results A total of 39 nonrandomized studies were included (714 patients; 88.1% males, 95% confidence interval [CI] 84.5-91.7; weighted mean age 75.76 years, 95% CI 74.11-77.4). Overall estimated technical success (TS) and clinical success (CS) rates were 93.2% (95% CI 90.5-95.8) and 88.2% (95% CI 84.5-91.9), respectively. Two hundred eighteen patients underwent proximal extension (98.1% TS, 95% CI 96.3-99.8), 131 chimney EVAR (93.9% TS, 95% CI 89.9-97.9), 97 fenestrated EVAR (86.2% TS, 95% CI 77.3-95.1), 90 open conversion (96.5% TS, 95% CI 93-100), 71 embolization (95.2% TS, 95% CI 90.4-100), 35 endostapling (57.2% TS, 95% CI 14.1-100), and 72 conservative treatment (75.4% CS, 95% CI 56.4-94.5). Estimated overall 30-day mortality was 3.2% (95% CI 1.7-4.7), and it was higher for patients undergoing open surgery (6.6%, 95% CI 1.7-11.5). Overall, endoleak resolution during the mean follow-up of 19.4 months (95% CI 15.45-23.36) was maintained in 91% of the patients (95% CI 87.7-94.3). Conclusions T1aEL repair appeared generally feasible, with good early to midterm outcomes. Different treatments are available, and the choice should be based on endoleak characteristics, aortic anatomy, and the patient's surgical risk. Conservative treatment and endoleak embolization should be considered only in selected cases, such as low-flow endoleaks and unfit patients.

In small animal practice, prostatic diseases are increasingly encountered. All dogs may experience prostatic disease, but particular care should be addressed to breeding dogs, in which prostatic affection may lead to decrease in semen quality and fertility. The most common prostatic disease is the benign prostatic hyperplasia (BPH) followed by prostatitis, prostatic neoplasia and prostate squamous metaplasia. These diseases do not have pathognomonic symptoms, therefore, making a correct diagnosis may not be easy. An accurate clinical examination and a correct diagnostic protocol are essential in order to begin the most appropriate treatment, and also to do a good prophylaxis where it is possible. BPH therapy is usually recommended when mild-severe signs are present or if symptoms disturb the patient. New therapeutic approaches, both medical and surgical, allow to maintain fertility in most animals with prostatic disorders. Prostate cancer is relatively infrequent. Elective therapy is the surgical one, but it is considered palliative and can result in important post-operative complications. The aim of this paper is to lay down the most appropriate diagnostic process describing the aetiologies of prostatic disease, their symptoms, the right investigative tools and therapy.

Objective: The aim of this observational study was to evaluate the effects of two different protein intake regimes on feeding tolerance, in-hospital growth, anthropometric data and psychomotor outcome up to 24 months corrected age (CA) in extremely low birth-weight (ELBW; birth weight < 1000 g) infants.Methods: During the period 2008-2013, 52 ELBW infants admitted at birth to two Neonatal Intensive Care Units of Emilia Romagna (Italy) were fed according to different protocols of protein fortification of human milk: an estimated protein intakes at maximum fortification levels of 3.5 gr/kg/day in the Standard Nutrition Population-SNP group (n = 26) and 4.8 g/kg/day in the Aggressive Nutrition Population-ANP group (n = 26). During hospitalization, infants' growth, biochemical indices of nutritional status, enteral intake, feeding tolerance, clinical history and morbidity were evaluated. After discharge, anthropometric data and psychomotor outcome, evaluated by Revised Griffiths Mental Development Scales (GMDS-R) 0-2 years, were assessed up to 24 months CA.Results: During hospitalization, the ANP group showed significantly higher weight (18.87 vs. 15.20 g/kg/day) and head circumference (0.70 vs. 0.52 cm/week) growth rates compared to SNP, less days of parenteral nutrition (7.36 +/- 2.7 vs. 37.75 +/- 29.6) and of hospitalization (60.0 +/- 13.3 vs. 78.08 +/- 21.32). After discharge, ANP infants had a greater head circumference compared to SNP (45.64 +/- 0.29; 46.80 +/- 0.31). Furthermore, the General Quotient of GMDS-R mean scores in the SNP group significantly decreased from 12 to 24 months CA, while no difference was seen in the ANP group.Conclusions: Increased protein intake may provide short and long term benefits in terms of growth and neurodevelopment in human milk-fed ELBW infants.

Quadriceps weakness has been associated with knee osteoarthritis (OA). High-frequency localized muscle vibration (LMV) has been proposed recently for quadriceps strengthening in patients with knee OA. The purpose of this study was (a) to investigate the clinical effectiveness of high-frequency LMV on quadriceps muscle in patients with knee OA and (b) to disentangle, by means of surface electromyography (sEMG), the underlying mechanism. Thirty patients, aged between 40 and 65 years, and clinically diagnosed with knee OA were included in this randomized, controlled, single-blinded pilot study. Participants were randomly assigned to two groups: a study group treated with LMV, specifically set for muscle strengthening (150 Hz), by means of a commercial device VIBRA, and a control group treated with neuromuscular electrical stimulation. Clinical outcome was measured using the Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, knee range of motion, Timed Up and Go test, and Stair climbing test. To assess changes in muscle activation and fatigue a subgroup of 20 patients was studied with the use of sEMG during a sustained isometric contraction. The LMV group showed a significant change in Western Ontario and McMaster Universities Osteoarthritis Index score, Visual Analogue Scale score, Timed Up and Go test, Stair Climbing Test, and knee flexion. These improvements were not significant in patients treated with neuromuscular electrical stimulation. sEMG analysis suggested an increased involvement of type II muscle fibers in the group treated with LMV. In conclusion, the present study supports the effectiveness of local vibration in muscle function and clinical improvement of patients with knee OA.

Background Apnoea of prematurity (AOP) frequently recurs in preterm infants. We have previously shown that a significant but variable proportion of AOP is induced by gastro-oesophageal reflux (GOR). Aim The aim of this study is to evaluate the efficacy of sodium alginate in reducing the frequency of GOR-related AOP. Subjects Twenty-eight preterm infants with AOP were studied by a six-hour recording of combined multichannel intraluminal impedance and pH monitoring and polysomnography, including two three-hour postprandial periods: sodium alginate was given after one single meal named as drug-given (DG) meal, while the other as drug-free (DF). Results During 165 h of registration, 715 apnoeas were recorded, 368 after-DG and 347 after-DF (p = .99); furthermore, 851 GOR episodes were detected, 315 after-DG and 536 after-DF (p = .001). No differences in the number of AOP were found between DG and DF. A significant reduction in the number of acid GORs and in acid exposure was found during DG, while the administration of sodium alginate didn't influence non-acid GOR indexes. The frequency of GOR-related apnoeas didn't differ between DG and DF. Discussion Sodium alginate doesn't reduce the total number of AOP nor GOR-related apnoeas. On the other hand, it reduces acid GOR features, while it had no effect on non-acid GOR indexes.

Background Protein content of preterm human milk (HM) is relatively low and extremely variable among mothers: thus, recommended protein intake is rarely met. Objectives To evaluate in a NICU setting if HM protein content after standard fortification meets the recommended intake, and also to check the effect of fortification on the osmolality of HM, as an index of feeding intolerance. Methods Protein content of 34 preterm HM samples was evaluated by a bedside technique (Near-Infrared-Reflectance-Analysis — NIRA); osmolality was also checked. Seventeen samples were fortified with Aptamil BMF, Milupa (Group A) and 17 with FM85, Nestle (Group B). Fortification was performed as recommended by the manufacturer (“full fortification [FF]”) and also with a lower amount of fortifier (“low-dose fortification [LF]”). After fortification, actual protein content was calculated and compared to that needed to meet recommended intake (2.33–3 g/dl), and osmolality was measured. Results After FF, protein content was above 3 g/dl in none of the samples, and below 2.33 g/dl in 16/34 samples (11 in Group A, 5 in Group B). After LF, protein content was above 3 g/dl in none of the samples and below 2.33 g/dl in 32/34 samples (15 in Group A, 17 in Group B). Osmolality exceeded 400 mOsm/kg in 19 samples after FF (10 in Group A, 9 in Group B) and in 2/34 samples after LF (1 in each group). Conclusion HM protein content after standard fortification fails to meet the recommended intake for preterm infants in approximately half of the cases.

Preterm human milk (HM) may provide insufficient energy and nutrients and thus may need to be fortified. Our aim was to determine whether fat content, protein content, and osmolality of HM before and after fortification may affect gastroesophageal reflux (GER) in symptomatic preterm infants.: Gastroesophageal reflux was evaluated in 17 symptomatic preterm newborns fed naïve and fortified HM by combined pH/intraluminal-impedance monitoring (pH-MII). Human milk fat and protein content was analysed by a near-infrared reflectance analysis. Human milk osmolality was tested before and after fortification. Gastroesophageal reflux indexes measured before and after fortification were compared and were also related to HM fat and protein content and osmolality before and after fortification.: An inverse correlation was found between naïve HM protein content and acid reflux index (RIpH: P = 0.041, rho =-0.501). After fortification, osmolality often exceeded the values recommended for infant feeds; furthermore, a statistically significant (P0.05) increase in nonacid reflux indexes was observed.: Protein content of naïve HM may influence acid GER in preterm infants. A standard fortification of HM may worsen nonacid GER indexes and, due to the extreme variability in HM composition, may overcome both recommended protein intake and HM osmolality. Thus, an individualised fortification, based on the analysis of the composition of naïve HM, could optimise both nutrient intake and feeding tolerance.

Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the −209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (−209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C−) with significantly higher frequency than elderly controls. C− carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C− carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.

Purpose To analyse the modifications induced by two different platelet-rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology. Methods OA synoviocytes were cultured for 7 days in medium with different concentrations of either P-PRP (a pure platelet concentrate without leucocytes but with a limited number of platelets), L-PRP (a higher platelet concentrate containing leucocytes) or platelet-poor plasma (PPP). Gene expression of interleukin (IL)-1beta, IL-6, IL-8/CXCL8, tumour necrosis factor alpha, IL-10, IL-4, IL-13, metalloproteinase-13, tissue inhibitor of metalloproteinase (TIMP)-1, (TIMP)-3, (TIMP)-4, vascular endothelial growth factor, transforming growth factor beta1, fibroblast growth factor (FGF)-2, hepatocyte growth factor (HGF), hyaluronic acid (HA) synthases (HAS)-1, (HAS)-2, and (HAS)-3 was analysed by RT-PCR. HA production was determined in culture supernatants by ELISA. Results IL-1β, IL-8 and FGF-2 were significantly induced by L-PRP compared to both P-PRP and PPP; HGF was down-modulated by L-PRP versus both P-PRP and PPP, and an inverse dose–response influence was shown for all preparations. Expression level of TIMP-4 was lower in the presence of L-PRP compared with P-PRP. HA production and HAS gene expression did not seem to be modulated by PRP. Conclusions L-PRP is able to sustain the up-regulation of proinflammatory factors, (IL-1beta, IL-8 and FGF-2), together with a down-modulation of HGF and TIMP-4 expression, two factors that have been recognized as anti-catabolic mediators in cartilage, thus supporting the need to further optimize the PRP preparations to be applied in clinical practice.

Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position −174 of the IL6 gene promoter (IL6−174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n = 824) were used to study the associations of baseline sIL6 with the IL6−174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR) = 3.04; 95% confidence interval (CI): 1.48–6.25] and absence of PMD [HR = 3.91; 95%CI: 1.42–10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR = 2.30; 95%CI: 1.09–4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25–3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR = 0.31, 95%CI: 0.13–0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6−174 C-allele does not seem to have direct detrimental effects on survival in older age.

The cross-sectional association of functional impairment with several peripheral blood inflammatory markers (increased C-reactive protein (CRP), fibrinogen and leucocyte count, decreased cholesterol and albumin) was studied in 739 elderly community-dwellers. Functional measures included Tinetti test for gait and balance, and basic and Instrumental Activities of Daily Living. When considering each marker individually, only increased CRP was inversely associated with all functional measures independently of demographics, lifestyle, and comorbidity (P0.05). When considering the sum of positive markers, having more than one marker was also inversely associated with all functional measures (P0.05), but no clear gradient of impairment was found across increasing numbers of markers. When considering specific combinations of markers, having both increased CRP and at least another positive marker had a stronger association with functional impairment (P0.01 for all measures) than increased CRP alone (P0.05), or other positive markers alone or in combination (P0.05). In conclusion, in elderly individuals, peripheral blood markers of inflammation are associated with functional impairment independently of potential confounders. A specific combination of CRP with other markers provides a better correlate of functional impairment than both individual markers or a simple count of positive markers.

Objective: To assess the reliability and reproducibility of fetal humerus length in the diagnosis of trisomy 21. Methods: Cohort study inclusive of 22 trisomy 21 fetuses, who underwent ultrasonographic examination between 14 and 22 weeks’ gestation, and 457 euploid controls. Regression analysis was performed for humerus length as function of biparietal diameter. Based on the generated regression equation in euploid fetuses, expected values of humerus length for a given biparietal diameter were calculated. The ratios of observed to expected (O/E) humerus length values were compared between euploid and trisomy 21 fetuses using Student’s t test. Receiver operating characteristic (ROC) curve analysis was used to detect optimal thresholds of O/E humerus length for diagnosis of trisomy 21. In addition, a MEDLINE search was conducted for articles published on humerus length as predictor of trisomy 21. Results: No differences were present between the regression lines of trisomy 21 and euploid fetuses (mean ± standard deviation O/E humerus length in euploid and aneuploid fetuses: 1.00 ± 0.10 vs. 0.97 ± 0.11, p = 0.21). The optimal threshold O/E humerus length Conclusions: The ability of humerus length to predict trisomy 21 is inconsistent. Only institutions with locally generated regression equations and documented predictive ability of this marker should utilize humerus length as a screening test for trisomy 21, alone or incorporated into diagnostic algorithms with serum or other sonographic markers of trisomy 21. The diagnostic ability of humerus length in low risk populations is currently unknown.

Measurement of femur length (FL) has been advocated as part of a genetic sonogram for the prediction of Down syndrome (DS). However its predictive ability has been inconsistent. We have studied the diagnostic value of this sonographic parameter in a prospective cohort of women with singleton gestations undergoing genetic sonogram between 14 and 22 weeks because of advanced maternal age or family history of aneuploidies. Genetic sonograms were performed at a mean gestational age of 17.0 weeks (range 14–22). DS was diagnosed in 30 fetuses, while 888 were euploid. Mean±SD observed/expected (O/E) values of FL (1.00±0.10 versus 0.97±0.01, p=0.07) were not significantly different between euploid and DS fetuses. Comparison of the regression equations of FL versus biparietal diameter revealed that while the intercepts were not significantly different between euploid and DS fetuses, the difference in slopes reached significance (p=0.04) suggesting that the predictive ability of FL may increase with advancing gestational age. In addition, a MEDLINE search (National Library of Medicine) was conducted for articles published between 1985 and 1998 on fetal femur length in the prediction of trisomy 21. Review of the published literature on the subject suggests that FL is not a consistent or reliable sonographic predictor of DS. Published thresholds of FL should not be used outside of the Institution from which they originated, and each Institution should establish whether this parameter has predictive ability in its own population. Copyright © 2000 John Wiley & Sons, Ltd.

Immunity & ageing 10, 4 (2013). doi:10.1186/1742-4933-10-4, Published by BioMed Central, London

Human milk is the best feeding choice for preterm infants, as it offers protection against sepsis and other infections (particularly diarrhoea and acute otitis media) [1] and against necrotizing enterocolitis (NEC) [2], thanks to its various bioactive and immunomodulatory components. Furthermore, human milk feeding is related to long-term improved neurocognitive development [3]. It has a beneficial role in facilitating and improving adaptation to extrauterine life; its components also have the effect of promoting psychomotor and behavioural development [4].

Background: Apnea of prematurity (AOP) occurs frequently in preterm infants and a variable proportion of AOP can be induced by gastroesophageal reflux (GER). Conservative treatment, including dietary modifications, should be the first-line approach for both GER and GER-related apneas in this population. Objectives: To evaluate the efficacy of a starch-thickened preterm formula (PF) in reducing the frequency of apneas related to GER. Methods: Preterm infants with AOP were studied by combined impedance and pH monitoring and polysomnography. The 6-hour study period included two feeds, one of a commercially available PF and one of the same formula thickened with amylopectin (TPF). GER indexes, apneas and GER-related apneas detected after TPF and PF feeds were compared by Wilcoxon signed-rank test. Results: 24 infants were studied. During 140 h of registration, 289 apneas (147 after TPF and 142 after PF; p = 0.876), and 861 GER episodes (400 after TPF and 461 after PF; p = 0.465) were recorded. No difference in the number of AOP was found between TPF and PF. A significant reduction in acid exposure was found after TPF; there was no influence on non-acid GER indexes. The frequency of GER-related apneas did not differ between TPF and PF. Conclusions: A formula thickened with amylopectin did not reduce the number of AOP or GER-related apneas. It reduced acid GER features but had no effect on non-acid GER indexes. Future research should focus on exploring different conservative strategies to treat GER-related apneas in preterm infants.

BACKGROUND: Gastro-oesophageal reflux (GOR) is common in preterm infants; conservative interventions (i.e. dietary changes) should represent the first-line approach. AIM: To evaluate by combined pH and impedance monitoring (pH-MII) the effect of a new preterm formula thickened with amylopectin (TPF) on GOR features in symptomatic preterm infants. METHODS: Twenty-eight symptomatic preterm newborns underwent a 24-hour pH-MII; each baby received eight meals (four of TPF and four of a preterm formula [PF]). GOR indexes (number, acidity, duration and height of GORs) after TPF and PF meals were compared by Wilcoxon Signed Ranks Test. Viscosity of PF and TPF was measured. RESULTS: TPF significantly decreased the number of acid GORs detected by pH-monitoring (TPF vs. PF: median 20 vs. 24.5, p = 0.009), while it had no influence on Reflux Index (RIpH), nor on acid and non-acid GOR indexes detected by MII, GOR physical features, and GOR height. TPF's viscosity was extremely higher than PF's, and further increased at pH 3 after the addition of pepsin. CONCLUSIONS: The new formula was found to reduce the number of acid GORs detected by pH-monitoring; it did not reduce neither total oesophageal acid exposure nor non-acid GORs. At present its extended clinical use cannot be recommended.

Detecting code smells in the code and consequently applying the right refactoring steps when necessary is very important to improve the quality of the code. Different tools have been proposed for code smell detection, each one characterized by particular features. The aim of this paper is to describe our experience on using different tools for code smell detection. We outline the main differences among them and the different results we obtained.

Type I mucopolysaccharidosis (MPS I) is a lysosomal storage disorder caused by the deficiency of α-L-iduronidase, which results in glycosaminoglycan accumulation in tissues. Clinical manifestations include skeletal dysplasia, joint stiffness, visual and auditory defects, cardiac insufficiency, hepatosplenomegaly, and mental retardation (the last being present exclusively in the severe Hurler variant). The available treatments, enzyme-replacement therapy and hematopoietic stem cell (HSC) transplantation, can ameliorate most disease manifestations, but their outcome on skeletal and brain disease could be further improved. We demonstrate here that HSC gene therapy, based on lentiviral vectors, completely corrects disease manifestations in the mouse model. Of note, the therapeutic benefit provided by gene therapy on critical MPS I manifestations, such as neurologic and skeletal disease, greatly exceeds that exerted by HSC transplantation, the standard of care treatment for Hurler patients. Interestingly, therapeutic efficacy of HSC gene therapy is strictly dependent on the achievement of supranormal enzyme activity in the hematopoietic system of transplanted mice, which allows enzyme delivery to the brain and skeleton for disease correction. Overall, our data provide evidence of an efficacious treatment for MPS I Hurler patients, warranting future development toward clinical testing.

Gastro-oesophageal reflux (GOR) is common in preterm infants. Combined multichannel intraluminal impedance and pH monitoring (pH-MII) is emerging as an useful tool to study both acid and non-acid GOR in this population. We aimed to highlight main advantages and limits of pH-MII in preterm infants and to test whether the inclusion of GOR episodes detected only by pH monitoring details better the features of GOR. Fifty-two symptomatic preterm infants underwent a 24-hour, continuous and simultaneous measurement of pH-MII. Each layout was analyzed using two different options: option 1 included GOR episodes detected by MII and then classified as acid or non-acid according to the associated pH change; option 2 included GOR episodes detected by MII and also GOR episodes detected only by pH sensor. By adopting option 1, a total number of 2834 GOR episodes was detected by MII: 2162 of them were characterized as non-acid and 672 were characterized as acid. The median (range) number of acid MII-GOR episodes was 10 (1-52); the median (range) number of non-acid MII-GOR episodes was 36.5 (2-119). Median (range) acid MII-GOR-bolus exposure index was 0.28% (0.02-2.73%); median (range) non-acid MII-GOR-bolus exposure index was 1.03% (0.06-38.15%). By adopting option 2, an average of 53.2 acid GOR episodes and an average of 11% oesophageal exposure to acid GOR more than by option 1 was detected. An accurate and detailed description of GOR in preterm infants can be obtained only by including in the analysis all acid GOR episodes detected by pH sensor.

BACKGROUND: Many biomaterials are proposed for sinus floor lifting and grafting in the posterior maxilla for insufficient bone volume (BV). The aim of this study was to compare the use of magnesium-enriched hydroxyapatite (mHA) versus autogenous bone graft (AB) for maxillary sinus lift procedures by histomorphometric and ex vivo gene expression profiling. METHODS: Fifteen patients requiring bilateral maxillary sinus augmentation received autologous bone particles (group A) and mHA (group B) (split-mouth design). Five months later, implants were placed, and biopsies were obtained. Bone specimens were analyzed by histomorphometry, BV and vital bone (VB) percentages were calculated, and ex vivo osteoblast expansion followed by highly sensitive osteoblast specific gene expression profiling for cbfa1, osteocalcin, osteopontin, collagen type I, receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG) by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) were performed. Comparisons were made using the Student t test. RESULTS: After healing with no complications, BV was comparable in the two groups (80.79% +/- 14.27% for autologous versus 76.72% +/- 11.47% for mHA; P = not statistically significant), but VB was lower in the mHA group (29.65% +/- 9.81% versus 78.40% +/- 16.72%; P

Aims. Human milk (HM) is considered a better choice than formula also for preterm infants’ nutrition, because it provides unique nutritional components, contributes to host defences, exerts trophic effects on gastrointestinal tract and promotes maternal-infant bonding; furthermore, feeding human milk to preterm infants may lead to short and long term beneficial effects. However, both preterm milk and banked term human milk provide insufficient amount of energy and essential nutrients needed for rapid growth and normal development as if infant had remained in uterus. For this reason, preterm HM is usually supplemented with commercially-produced multicomponent fortifiers (HMF): nonetheless, HM fortification such that intake really meets requirements is difficult, because HM protein and fat content is highly variable among mothers, gestational age at delivery, number of weeks after delivery, and time of day. To our knowledge, no previous studies have evaluated the influence of human milk nutritional and chemical features, and neither the effect of fortification, on gastroesophageal reflux (GER), which is common in preterm infants. The aim of our study was to evaluate whether the features of HM before and after fortification affect the pattern of gastroesophageal reflux in symptomatic preterm infants. In particular, fat and nitrogen content and osmolarity of HM were correlated with GER features. Methods. We studied seventeen preterm infants with symptoms suggestive of GER (frequent regurgitations and/or post-prandial desaturations). Each patient underwent a twenty-four-hour, continuous and simultaneous measurement of intra-esophageal impedance and pH by Multichannel intraluminal impedance and pH monitoring (Sandhill Scientific). During the study period, seven meals were given: the first one was always of unfortified HM, to avoid a potential carry over effect due to the features of previous feeding. The other six were divided into three couples (two meals of unfortified HM, two meals ofHM+ FM85 Nestlé 3% [Vevey, Switzerland], and two meals ofHM+ FM85 Nestlé 5%). The order of the three couples of meals was randomly assigned. Mother milk’s fat and nitrogen content was analysed by a Near Infrared Reflectance Analysis (NIRA). Furthermore, the osmolarity of each mother’s milk was tested. Results. An inverse correlationwas found between human milk protein content and the main reflux indexes, especially the acid ones, measured after the two HM meals. No correlation was found between fat content and any reflux index, neither between human milk’s fat and protein content. No correlationwas found between osmolarity values and GER indexes.We further analysed whether HM composition continued to be related to the pattern of GER also after fortification: we found that the correlation between HM protein content and the main GER indexes detected after fortification tended to reverse.We calculated the difference between RIpH detected after HM+HMF3% and the one detected before fortification (RIpH 3%), and also the difference between RIpH detected after HM+HMF5% and the one detected before fortification ( RIpH 5%): these indexes showed a significant direct correlation with HM protein content. In other words, patients who had a lowprotein content of naïveHMshowed a reduction of GER indexes after fortification. On the contrary, patients who had a high protein content of naïve HMshowed an increase of GER indexes after fortification. Conclusions. The evaluation of nutritional content of pretermHMmay allowa more precise and individualised fortification regimen, and thus improve nutritional management of preterm infants with gastroesophageal reflux.

International audience; BACKGROUND: Aging is associated with low-grade elevation of circulating inflammatory markers, leading to increased risk of morbidity and mortality. The Mediterranean diet has been suggested as a determinant of longevity. In the current study, we investigated the impact of the Mediterranean diet on inflammatory status in old subjects. METHODS: Within the ZINCAGE study, 957 healthy old subjects (>or=60 years old) from five European countries were recruited. Plasma interleukin (IL)-6, IL-8, monocyte chemoattractant protein, tumor necrosis factor-alpha, high-density lipoprotein cholesterol (HDL-C) and erythrocyte sedimentation rate (ESR) were measured. Dietary data were collected applying a food frequency questionnaire and were used to estimate adherence to the Mediterranean diet. RESULTS: The Italians presented the greatest adherence to the Mediterranean diet, while the Polish the poorest. In females, higher diet score was significantly associated with lower body mass index and ESR and higher HDL-C levels (beta=-0.127, p=0.003; beta=-0.144, p=0.001; beta=0.144, p=0.029, respectively). In males, diet score was negatively associated with IL-8 levels (beta=-0.101, p=0.044). The Mediterranean diet was associated with reduced IL-8 concentrations in Greeks (beta=-0.213, p=0.007). CONCLUSIONS: There were significant effects of the components of the Mediterranean diet on inflammation markers. The Mediterranean diet score is useful in assessing nutritional influence on immune status.

Incidence studies of blood inflammatory markers as predictors of dementia in older age are few and did not take into account hyperhomocysteinemia, although this condition is associated with both inflammation and increased risk of dementia. We investigated the relationships of baseline serum C-reactive protein (CRP), serum interleukin 6 (IL6), plasma alpha-1-antichymotrypsin, and hyperhomocysteinemia (defined as plasma total homocysteine>15 micromol/L) with risk of incident Alzheimer's disease (AD) and vascular dementia (VaD) in a dementia-free Italian population-based elderly cohort (n=804, 53.2% women, mean age 74 years) with 4 years of follow-up. No inflammatory marker, alone or in combination, predicted AD risk whereas the combination of high CRP and high IL6 was associated with risk of VaD (HR, 2.56; 95%CI, 1.21-5.50) independently of socio-demographic confounders, traditional risk factors and hyperhomocysteinemia. By contrast, in the same model, hyperhomocysteinemia was independently associated with AD (HR, 1.91; 95%CI, 1.02-3.56) but not VaD risk. Blood inflammatory markers are associated with increased VaD risk but do not predict AD, which seems selectively associated with hyperhomocysteinemia.

Aims. GER is common in preterm newborn, due to some promoting factors such the almost fixed lying position, the large fluid enteral intake, the frequent nurse handling and the use of permanent feeding tubes. Twentyfour- hour pH monitoring has traditionally represented the gold standard for GER detection: it recognizes GER episodes as a pH drop

Chemokines play an important role in orchestrating leukocyte recruitment and activation during inflammation. Given the ubiquity of chemokines involved in inflammatory tissue destruction, it is not surprising that they contribute to numerous human pathologies. Epidemiological studies have suggested that chronic low-grade inflammation is related to several diseases of ageing with an inflammatory pathogenesis (such as atherosclerosis, type 2 diabetes, osteoarthritis and Alzheimer’s disease) and to increased mortality risk. In this chapter, we will briefly review the properties of chemokines and their receptors and highlight the roles of these chemoattractants in the above selected diseases of ageing.

Objective: To estimate age- and sex-specific incidence of dementia, Alzheimer disease (AD), and vascular dementia (VaD) in the Conselice Study of Brain Aging, an Italian prospective population-based study, and to assess whether poor education is a risk factor for dementia. Methods: In 1999 to 2000, the baseline study identified a dementia-free cohort of 937 subjects aged 65 years and older who were reexamined in 2003 to 2004 using a two-phase procedure. Results: Information was obtained for 91% of the subjects at risk; 115 incident cases of dementia were identified. Incidence rates per 1,000 person-years were 37.8 (95% CI = 30.0 to 47.7) for dementia, 23.8 (95% CI = 17.3 to 31.7) for AD, and 11.0 (95% CI = 7.2 to 16.9) for VaD. This translates into more than 400,000 new cases of dementia expected per year in Italy. Increasing age was an independent risk factor for both AD and VaD. Poor education was an independent risk factor for AD but not VaD. Sex did not affect dementia risk. Conclusions: In this Italian population-based cohort, incidence of dementia increased with age, and Alzheimer disease (AD) was the most frequent type of dementia. Poor education was associated with a higher risk of AD. Our incidence rates are higher than previously reported in Italy, and provide new estimates for projection of future burden of disease in Italy.

The aim was to delineate the significance and natural history of fetal arrhythmias and provide information about their management. A cohort of 114 infants with fetal arrhythmias detected during prenatal ultrasound (US) screening were studied. All subjects underwent echocardiography and were treated as clinically indicated. Postnatal outcome was obtained in 100% of infants until 1 year of age. The incidence of fetal arrhythmias was 0.3%. Among the 87 fetuses with atrial extrasystoles, 2.3% developed supraventricular tachycardia (SVT) in utero. Of the 10 SVT cases, only five required antiarrhythmic therapy in utero with digoxin and propafenone, which successfully restored sinus rhythm in 100% of fetuses, both nonhydropic and hydropic. Sinus bradycardia was associated with structural anomalies in 5 of 6 patients and only 2 of 4 fetuses with atrioventricular block survived. It is concluded that prognosis is good for most fetal tachyarrhythmias, whereas it is less favorable for bradyarrhythmias.

Recently, novel members of the TNF/TNF receptor superfamily, receptor activator of nuclear factor- kappa B ligand (RANKL), its receptor RANK, and the decoy receptor osteoprotegerin (OPG), have been identified as paracrine mediators of both the immune system and bone functions. The balance of RANK/RANK-L and OPG is critical for osteoclastogenesis modulation and physiological bone remodeling. In order to evaluate whether RANKL/OPG balance is modified by ageing, we analyzed, by imunoassay, systemic levels of OPG and sRANKL in healthy elderly subjects (age range from 70 to over 90 years) and in patients affected by two age-related diseases, osteoarthritis (OA) and polymyalgia rheumatica (PMR), characterized by bone metabolism alteration and involvement of the immune system. We demonstrated that (a) plasma concentrations of OPG increased significantly with age; (b) conversely, sRANKL significantly declined in the group of subjects aged between 81 and 90 years, being similar to the young controls in the other age groups; (c) in OA and PMR, circulating OPG did not differ from plasma levels found in age-matched control groups, while sRANKL concentration was significantly increased compared to controls. Hence, in ageing, the sRANKL/OPG system appears to be modified, with prominent changes in circulating OPG levels; in OA and PMR, the sRANKL/OPG balance alteration was shown to be mainly due to the increase of plasma sRANKL concentration.

Increased levels of plasma total homocysteine (tHcy) may play a role in both cardiovascular diseases (CVD) and old-age dementias via enhancement of vascular inflammation. However, the association between plasma tHcy and serum C-reactive protein (sCRP), taken as a marker of low-grade inflammation, is still uncertain. We investigated this association in normal aging, CVD, and dementia, and examined whether it was modified by the presence of two major comorbid diseases of older age: chronic obstructive pulmonary disease (CPOD) and peptic ulcer (PU). Six hundred-twenty-seven individuals agedor = 65 yr (74+/-7 yr) were selected for this study: 373 healthy controls; 160 patients with CVD but no evidence of comorbid diseases (CVD+/comorbidity-); 46 patients with CVD and concurrent CPOD and/or PU (CVD+/comorbidity+); and 48 patients with dementia. A positive association between plasma tHcy and serum CRP, independent of several confounders (socio-demographic status, known tHcy and sCRP determinants, inflammation markers, traditional vascular risk factors), was found for CVD+/comorbidity+ (p=0.001; not affected by dementia type) and dementia (p=0.001; not affected by dementia type), but not for CVD+/comorbidity- and controls. The results suggest that the association between plasma tHcy and sCRP is more an aspecific reflection of poor health than a specific correlate of vascular inflammation.

Objective To assess the clinical relevance of adnexal masses in pregnancy and the usefulness of ultrasound in their management. Design A prospective study on pregnancy complicated by adnexal masses. Setting Department of Obstetrics and Gynaecology in Italy. Population 6636 women with pregnancy in utero followed in our clinic from January 1996 to December 1999. Methods From 1996 to 1999, all ovarian cysts with a diameter exceeding 3 cm were prospectively recorded and followed. The management was expectant except in case of symptoms or suspected malignant features. Cysts suggestive of borderline tumours were treated expectantly. Main outcome measures Clinical relevance of adnexal masses in pregnancy, the outcome of these pregnancies and the usefulness of ultrasound examination in their management. Results We detected 82 cysts in 79 of 6636 women (1.2 in 100 term pregnancies). Sixty-eight women were asymptomatic at the time of diagnosis, whereas 11 (13.9%) were diagnosed because of pain. Diagnosis occurred in the first trimester for 57 cases and in the second or third trimester in 22 (27.8%). One-half of the cysts were simple and anechoic at ultrasound. Fifty-seven had a diameter not exceeding 5 cm. Forty-two cyst resolved in pregnancy without treatment. Three cysts required surgery within few days (torsion). One woman required laparotomy at the 37th week of gestation, due to torsion. When one case of termination was excluded, 78 women delivered at term (66 vaginally, 12 by caesarean section). Nineteen women underwent surgery after pregnancy. We recorded three Stage Ia borderline tumours, accounting for 3/82 cysts (3.6%) and 3/30 persisting masses (10%). Conclusions Ultrasound allows definition of ovarian cysts in pregnancy and this positively impacts on management. The incidence of cancer among persistent masses is lower than previously reported. Acute complications in stable cysts are extremely uncommon after the first trimester. An expectant management is successful in the majority of cases and should be considered more often. Routine removal of persistent cysts is not justified.

Objective: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. Study Design: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. Results: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). Conclusion: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient. (Am J Obstet Gynecol 2000;182:972-7.)

Nuchal fold thickness is the best ultrasonographic predictor of fetal trisomy 21. However, the risk assigned on the basis of the commonly used threshold of nuchal fold thickness/=6 mm does not take into consideration the significant associations between nuchal fold thickness and gestational age and between maternal age and Down syndrome. We propose a new method of calculating Down syndrome probability that takes into account both gestational age at examination and previously assessed probability of Down syndrome.Nuchal fold thickness was measured at ultrasonographic examination at 14 to 22 weeks' gestation without previous knowledge of the fetal karyotype. Nuchal cystic hygromas were excluded from analysis. Statistical analyses included correlation, logistic regression to control for other ultrasonographic predictors of trisomy 21 and for maternal age, receiver operating characteristic curve, and likelihood ratios (defined as the ratio of the sensitivity to the false-positive rate). P.05 was considered significant.Mean gestational age at ultrasonography was 16.9 weeks' gestation (range, 14-22 weeks' gestation). Mean (+/-SD) nuchal fold thickness in fetuses with trisomy 21 (4.7 +/- 1.6 mm; n = 29) was greater than in euploid fetuses (3.2 +/- 0.9; n = 780; P.001). Logistic regression analysis established that nuchal fold thickness was a significant predictor of trisomy 21 independent both of the other ultrasonographic markers and of maternal age (P.001). Regression analysis showed that nuchal fold thickness was significantly correlated with gestational age among both fetuses with trisomy 21 and euploid fetuses and that the regression line of fetuses with trisomy 21 had a slope similar to that of euploid fetuses. The difference between observed and expected nuchal fold thicknesses on the basis of the biparietal diameter (as a function of gestational age) was used to obviate the confounding effect of gestational age. Differences between observed and expected nuchal fold thicknesses were then used to calculate likelihood ratios. These likelihood ratios could then be multiplied by the individual prior probability to obtain a patient-specific Down syndrome probability.Nuchal fold thickness is correlated with gestational age in both euploid fetuses and fetuses with Down syndrome. Use of the difference between observed and expected nuchal fold thicknesses to determine likelihood ratios allows the calculation of individual posterior probabilities of Down syndrome that take into consideration both gestational age and maternal age.

Aim. Apnoea of prematurity (AOP) is a perplexing disorder of respiratory control that is very common in preterm infants and requires therapeutic intervention to avoid potential morbidity. The existence of a relationship between gastroesophageal reflux (GER) and AOP in preterm infants is still controversial. We aimed to evaluate the relationship between GER and apnoeas in preterm newborns, by the simultaneous and synchronized use of combined Multichannel Intraluminal Impedance and pH-monitoring (pH-MII), and polysomnography (PSG). Methods. Twenty-six preterm infants were studied as they had recurrent apnoeas. They underwent a 6-h simultaneous and synchronized recording of polysomnography and pH-MII. Each registration involved 2 post-prandial periods lasting 3 h each. Polysomnography detects and characterizes apnoeas, desaturations and bradycardia, by recording of breathing movement, nasal airflow, electrocardiogram, pulse oximeter saturation. All apnoeas lasting more than 5 s were considered, and classified as central (CA), obstructive (OA) and mixed apnoeas (MA). By pH-MII we registered acid/non acid GER. The temporal association between GER and apnoea was analysed by the frequency of apnoea in the 30 s preceding and following the onset of GER episodes. Apnoeas detected within thirty seconds after GER were defined GER-triggered. Results. One-hundred-fifty-four apnoeas out of 1136 were detected within 30 second before and/or after the onset of a GER episode. The frequency of apnoea during the 1-min time around the onset of a GER episode (mean 0.17/min; range [0–0.84/min]) was significantly different (p = 0.03) from the one detected during the GER-free period (0.12/min [0–0.43/min]), which is defined as the time difference between the total recording time and the time around all GER episodes. The frequency of apnoea before the onset of GER (0.10/min [0–0.69/min]) did not differ from the one detected during GER-free period (p = 0.17). The frequency of apnoea occurring after the onset of GER (0.25/min [0–1/min]) was higher than the one detected in the GER-free period (p = 0.02), and also than the one detected before the onset of GER (p = 0.01). A great inter-individual variability was documented in the ratio of GER-triggered apnoeas to the total number of apnoeas (median 10.34%, range: 0–20%), as well as in the ratio of GER-triggered apnoeas to the total number of GERs (median 5.77%, range: 0–50%). The increase of apnoeas after GER, defined as the difference between the number of apnoeas detected in the 30 s after GER and the one detected 30 s before GER, was calculated (median 2; range: −2/+8). A significant correlation was found between this difference and the total number of apnoeas (ρ = 0.425, p = 0.034); on the other hand, no correlation was documented between total number of GERs and GER-triggered apnoeas (ρ = 0.019; p = 0.930). Conclusion.We found that, in preterm infants with recurrent apnoeas, these events occur more frequently soon after GER than in the period immediately before GER or GERfree. This suggests that the relationship between GER and AOP is not simply by chance. The ratio of GER-triggered apnoeas to the total number of apnoeas is widely variable. Furthermore, the wide variability in the ratio of GERtriggered apnoeas to the total number of GERs documents that in some newborns a GER episode more likely evokes an apnoea. Patients who had the most significant increase of apnoeas after GER also had the highest number of total apnoeas: in other words, in the most unstable infants also GER episodes can easily act as a trigger event for apnoeas.Onthe other hand, the lack of correlation between GER-triggered apnoeas and total number of GERs highlights that the severity of GER is not predictive by itself of the risk of reflex apnoeas.

MCI is a nosological entity proposed as an intermediate state between normal aging and dementia. The syndrome can be divided into two broad subtypes: amnestic MCI ( aMCI) characterized by reduced memory, and non- amnestic MCI ( naMCI) in which other cognitive functions rather than memory are mostly impaired. aMCI seems to represent an early stage of AD, while the outcomes of the naMCI subtypes appear more heterogeneous - including vascular dementia, frontotemporal dementia or dementia with Lewy bodies- but this aspect is still under debate. MCI in fact represents a condition with multiple sources of heterogeneity, including clinical presentation, etiology, and prognosis. To improve classification and prognosis, there is a need for more sensitive instruments specifically developed for MCI as well as for more reliable methods to determine its progression or improvement. Current clinical criteria for MCI should be updated to include restriction in complex ADL; also the diagnostic and prognostic role of behavioral symptoms and motor dysfunctions should be better defined. A multidisciplinary diagnostic approach including biological and neuroimaging techniques may probably represent the best option to predict the conversion from MCI to dementia. In this review we discuss the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of MCI, with specific attention to possible markers of conversion to dementia.