The biological underpinnings of perinatal depressive symptoms: A multi-systems approach.

BACKGROUND: Well-established evidence exists of an association between depressive symptoms and alterations in the stress and inflammatory response systems; however, the picture is far less coherent during the perinatal period. This study combines the assessment of multiple stress and inflammatory biomarkers in late pregnancy and after delivery in order to investigate cross-sectional and prospective associations with perinatal depressive symptoms. METHODS: One-hundred-ten healthy women were assessed in late pregnancy (mean gestational age=34.76; SD=1.12) and 89 were re-evaluated after delivery (mean hours after delivery=52.36; SD=19.70) for depressive and anxiety symptoms through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. Serum Interleukin-6 (IL-6), C-Reactive Protein (CRP) and diurnal salivary cortisol levels were measured on both occasions, while diurnal salivary alpha amylase (sAA) levels were assessed in late pregnancy. RESULTS: Using Hierarchical Linear Models, higher depressive symptoms were found to be associated with higher IL-6 levels, lower morning cortisol levels and a flatter cortisol diurnal slope during pregnancy, while adjusting for potential confounders. No significant associations were found after delivery or with change in biomarker levels from pre- to post-partum. Furthermore, preliminary evidence of a positive association between inflammation and stress markers in women with higher antenatal depressive symptoms was found. LIMITATIONS: The sample was relatively small and highly selected, thus limiting generalizability of the findings. CONCLUSIONS: Results emphasize the need for an integrated multi-systems approach to the understanding of the biological underpinnings of perinatal depression and suggest that the stress-immune interactions represent a promising avenue for future endeavor.

Beyond the HPA-axis: Exploring maternal prenatal influences on birth outcomes and stress reactivity.

Accumulating evidence suggests that antenatal maternal stress is associated with altered behavioral and physiological outcomes in the offspring, however, whether this association is causal and the underlying biological mechanisms remain largely unknown. While the most studied mediator of maternal stress influences on the fetus has generally been cortisol, alternative novel markers of stress or inflammation warrant further consideration. The current investigation explored the influence of variations in self-reported symptoms of distress, stress hormones and inflammatory markers on infant birth outcomes and early stress regulation. The sample consisted of 104 pregnant women (mean gestational age = 34.76; SD = 1.12) and their healthy newborns. Maternal self-reported symptoms of depression and anxiety were evaluated through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory and levels of serum Interleukine-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) were measured in late pregnancy. Newborns' cortisol and behavioral response to the heel-stick was assessed 48-72 hours after birth. The associations between maternal stress measures and infant birth outcomes and stress reactivity, adjusted for potential confounders, were examined through hierarchical linear regressions and hierarchical linear models. Higher maternal IL-6 levels were associated with smaller head circumference at birth, while diurnal sAA levels were positively associated with birthweight. Maternal diurnal cortisol was related to newborn's stress reactivity: a flatter infant cortisol response to the heel-stick was associated with greater maternal cortisol increases after awakening during pregnancy, while greater infant behavioural reactivity was related to a flatter maternal diurnal cortisol profile. The observational nature of these data does not allow for causal inferences but the current findings illustrate that antenatal factors related to alterations in maternal stress and immune response systems are associated with fetal growth and neonatal stress reactivity. This may have implications for later health and psychological outcomes.

Leisure and occupational physical activity at different ages and risk of endometriosis.

OBJECTIVE: Cohort and case-control studies have suggested that adult physical activity (PA) may lower endometriosis risk and improve symptoms, but evidence is still controversial. To add information on leisure and occupational PA impact, if any, on endometriosis risk, we have analyzed data from a small case-control study conducted in Milan (Italy). STUDY DESIGN: Ninety cases and 90 controls (median age 35 years, range 18-76) were compared. Endometriosis was laparoscopically diagnosed within the year before interview. Information on demographic variables, menstrual and reproductive history, occupational and recreational physical activity was collected. RESULTS: A consistent protective effect emerged between leisure PA and endometriosis risk. For <2-4 and ≥5h/week (reference no PA), the estimated odds ratios (ORs) were, respectively: 0.36 (95% CI 0.18-0.74) and 0.83 (95% CI 0.27-2.53) as regards PA in early adolescence; 0.31 (95% CI 0.15-0.63) and 0.78 (95% CI 0.25-2.38) as regards PA in teenage years; 0.34 (95% CI 0.12-0.94) and 0.33 (95% CI 0.08-1.28) for PA in adulthood. However, no significant trend was seen according to hours spent in leisure PA. Occupational PA did not show statistical significant differences among different types or across age classes. CONCLUSIONS: These results suggest that leisure PA in early adolescence, teenage years and adulthood may, to some extent, decrease the risk of endometriosis. In the interpretation of these results, however, the role of potential biases cannot be totally ruled out.

The requirements of a specialist Breast Centre.

INTRODUCTION: In recognition of the advances and evidence based changes in clinical practice that have occurred in recent years and taking into account the knowledge and experience accumulated through the voluntary breast unit certification programme, Eusoma has produced this up-dated and revised guidelines on the requirements of a Specialist Breast Centre (BC). METHODS: The content of these guidelines is based on evidence from the recent relevant peer reviewed literature and the consensus of a multidisciplinary team of European experts. The guidelines define the requirements for each breast service and for the specialists who work in specialist Breast Centres. RESULTS: The guidelines identify the minimum requirements needed to set up a BC, these being an integrated Breast Centre, dealing with a sufficient number of cases to allow effective working and continuing expertise, dedicated specialists working with a multidisciplinary approach, providing all services throughout the patients pathway and data collection and audit. It is essential that the BC also guarantees the continuity of care for patients with advanced (metastatic) disease offering treatments according to multidisciplinary competencies and a high quality palliative care service. The BC must ensure that comprehensive support and expertise may be needed, not only through the core BC team, but also ensure that all other medical and paramedical expertise that may be necessary depending on the individual case are freely available, referring the patient to the specific care provider depending on the problem. CONCLUSIONS: Applying minimum requirements and quality indicators is essential to improve organisation, performance and outcome in breast care. Efficacy and compliance have to be constantly monitored to evaluate the quality of patient care and to allow appropriate corrective actions leading to improvements in patient care.

Double innervation in free-flap surgery for long-standing facial paralysis.

OBJECTIVE: One-stage free-flap facial reanimation may be accomplished by using a gracilis transfer innervated by the masseteric nerve, but this technique does not restore the patient's ability to smile spontaneously. By contrast, the transfer of the latissimus dorsi innervated by the contralateral facial nerve provides the correct nerve stimulus but is limited by variation in the quantity of contraction. The authors propose a new one-stage facial reanimation technique using dual innervation; a gracilis muscle flap is innervated by the masseteric nerve, and supplementary nerve input is provided by a cross-face sural nerve graft anastomosed to the contralateral facial nerve branch. METHODS: Between October 2009 and March 2010, four patients affected by long-standing unilateral facial paralysis received gracilis muscle transfers innervated by both the masseteric nerve and the contralateral facial nerve. RESULTS: All patients recovered voluntary and spontaneous smiling abilities. The recovery time to voluntary flap contraction was 3.8 months, and spontaneous flap contraction was achieved within 7.2 months after surgery. According to Terzis and Noah's five-stage classification of reanimation outcomes, two patients had excellent outcomes and two had good outcomes. CONCLUSIONS: In this preliminary study, the devised double-innervation technique allows to achieve a good grade of flap contraction as well as emotional smiling ability. A wider number of operated patients are needed to confirm those initial findings.

Proportional incidence and radiological review of large (T2+) breast cancers as surrogate indicators of screening programme performance.

OBJECTIVES: Surrogate measures of screening performance [e.g. interval cancer (IC) proportional incidence] allow timely monitoring of sensitivity and quality. This study explored measures using large (T2+) breast cancers as potential indicators of screening performance. METHODS: The proportional incidence of T2+ cancers (observed/expected cases) in a population-based screening programme (Trento, 2001-2009) was estimated. A parallel review of 'negative' preceding mammograms for screen-detected T2+ and for all ICs, using 'blinded' independent readings and case-mixes (54 T2+, 50 ICs, 170 controls) was also performed. RESULTS: T2+ cancers were observed in 168 screening participants: 48 at first screen, 67 at repeat screening and 53 ICs. The T2+ estimated proportional incidence was 68% (observed/expected = 168/247), corresponding to an estimated 32% reduction in the rate of T2+ cancers in screening participants relative to that expected without screening. Majority review classified 27.8% (15/54) of T2+ and 28% (14/50) of ICs as screening error (P = 0.84), with variable recall rates amongst radiologists (8.8-15.2%). CONCLUSIONS: T2+ review could be integrated as part of quality monitoring and potentially prove more feasible than IC review for some screening services. KEY POINTS: • Interval breast cancers, assumed as screening failures, are monitored to estimate screening performance • Large (T2+) cancers at screening may also represent failed prior screening detection • Analysis of T2+ lesions may be more feasible than assessing interval cancers • Analysis of T2+ cancers is a potential further measure of screening performance.

Analysis of proportional incidence and review of interval cancer cases observed within the mammography screening programme in Trento province, Italy.

PURPOSE: The aim of this study was to assess the performance of the mammography screening programme in Trento Province, Italy, by analysing the interval cancers (IC) observed from 2001 to 2008. MATERIAL AND METHODS: IC were identified by linking screening archives with local cancer registry and pathology archives as well as with hospital discharge records. Proportional incidence was determined according to breast cancers expected in the absence of screening, estimated on the basis of patients/year at risk and age-specific incidence. The review of screening mammograms preceding ICs was performed by an external (three radiologists) and an internal (five radiologists) panel and aimed at assessing the proportion of IC reviewed as screening errors. Results were compared with European Community (EC) recommended standards. RESULTS: IC proportional incidence was 15.90% for the first year (EC standard <30%) and 25.77% for the second year (EC standard <50%) of the interval. At external review, 18.4% of cases were reviewed as screening errors (identified by at least two of three reviewers), whereas at internal review (identified by at least three of five reviewers) it was 17.4% (EC standard <20%). No significant difference was observed between external and internal review (mean recall rate 8.3% vs. 9.0%; mean identification rate 19.7% vs 19.6%). CONCLUSIONS: The study confirms good performance of the mammography screening programme in Trento Province, Italy. Comparable results of external and internal reviews suggest that the latter, no doubt easier to be implemented, might be adopted as a routine procedure to assess this early efficacy indicator.

'It's as if PBC didn't exist': the illness experience of women affected by primary biliary cirrhosis.

This study investigates the illness experience of women who are affected by primary biliary cirrhosis (PBC), a rare chronic liver disease which mostly affects women. Despite the fact that PBC is medically recognised, it shares many characteristics with other chronic and controversial conditions which may lead to delegitimation of the patient's experience of illness, impacting on the construction of the patient's self-identity. Twenty three women took part in semi-structured interviews. Data were analysed using interpretative phenomenological analysis and the analysis identified three themes that are interrelated and characterised by a dynamic of normalisation. The first theme, the delegitimation of women's experience, implies denial of patients' sick-role, trivialisation of fatigue and lack of consideration of patients' needs. The second theme, PBC as a challenge to women's social identity refers to how patients face delegitimation and manage the illness's consequences for relationships and social roles. The third theme, the need for biographical continuity, focuses on how patients construct their ill identities as a consequence of both the delegitimation and the challenges posed by PBC. Results are discussed in a gender perspective, highlighting how delegitimation and identity construction processes are influenced by women's social roles and conditions.

"CADEAT": considerations on the use of CAD (computer-aided diagnosis) in mammography.

Computer-aided diagnosis (CAD) has been extensively reported to increase sensitivity by about 10% when added to a single reading while increasing recall rate by 12%, and its current use can be safely recommended in clinical practice. CAD has been suggested as a possible alternative to conventional double reading in screening. Uncontrolled comparison is consistent and suggests that CAD is comparable to double reading in incremental cancer detection rate (CAD +10.6%, double reading +9.1%) and possibly better in recall rate (CAD +12.5%, double reading +28.8%). However, controlled studies comparing single reading + CAD to conventional double reading are not consistent and on average suggest a lower cancer detection rate (-5.1%) and a lower recall rate (-9.8%) for CAD. Scientific evidence is not sufficient for a safe recommendation of single reading + CAD as a current alternative to conventional double reading.

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size.

Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988-1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50-70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N+) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N+ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N+ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01-0.39) in the 2-7 mm size category to 0.95 (0.64-1.40) in the 18-22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase.

[A rationale basis for airways conditioning: too wet or not too wet? ]. / Una base razionale per il condizionamento delle vie aeree: umidificare troppo o non troppo?

Medical gases conditioning during mechanical invasive ventilation is nowadays a problem. In fact, in spite of conditioning guidelines, absolute humidity (AH) into 25-35 mg/l, clinical evaluation of the optimal level of airway humidification has not yet been established with certainty. Physiologically, during spontaneous respiration the airway hydric balance, inspiratory AH expiratory AH, is negative of 27 mg/l about. Usually the patients on mechanical ventilation have an expiratory AH of 32-33 mg/l. An overhumidification of inspired gases, positive airway hydric balance, gives anatomic-physiological alterations of airways and lung parenchyma. During invasive mechanical ventilation, the practice of active hot humidifiers has a positive or level airway hydric balance. We think that inspired AH must be equal to expired AH to maintain an airway hydric balance at least level. At last, the temperature of inspired gases, with active hot humidifiers, shouldn't exceed 32-34 degrees C.

A brief neuropsychological assessment for the differential diagnosis between frontotemporal dementia and Alzheimer's disease.

The neuropsychological performance (including measures of language, semantic memory, visual and spatial perception and executive functions) of a group of 14 patients with the clinical diagnosis of probable frontotemporal dementia was compared with that of a group of 14 patients with a clinical diagnosis of probable Alzheimer's disease. The aim was to identify a specific cognitive profile of frontotemporal dementia, which could be used to select a sensitive, short evaluation for the differential diagnosis with Alzheimer's disease. Both groups were severely impaired in most tasks, including those 'frontal lobe' tests which have been suggested to play an important role in differential diagnosis. Significant differences were found only for a minority of tests (oral praxis, visual-spatial perception, and verbal fluency). A logistic regression showed that a shortened testing procedure based on four tests (Rey-Osterreith complex figure test recall, phonemic fluency, oral apraxia, and cube analysis) achieved a 70% sensitivity and 80% specificity for the correct classification of patients in the frontotemporal dementia or Alzheimer's disease group. In conclusion, a brief neuropsychological evaluation including these four tests, as well as other measures sensitive to the frontal impairment, can be useful in the differential diagnosis between the two pathologies, along with the clinical data.

[Assessment of diagnostic accuracy of mammography carried out for secondary prevention. Results of a test with a sample caseload conducted by 75 Italian radiologists]. / Valutazione dell'accuratezza diagnostica nella mammografia eseguita con fini di prevenzione secondaria. Risultati di una prova su casistica campione sostenuta da 75 radiologi italiani.

PURPOSE: To report the results of a test performed by 75 volunteer radiologists involved in screening program in Italy. MATERIAL AND METHODS: The test includes 12 screening detected cancers and 6 cancers (4 screening detected and 2 interval lesions) with minimal signs at review of a previous negative mammogram. Data on previous experience in mammography (years of activity, years of screening activity, total number of mammograms read and number of mammograms read per year) were also collected. RESULTS: Standards for passing the test were at least 83.3% for sensitivity for screening detected cancers and at most 30% for recall rate among negative cases. Mean sensitivity was 83.9% (median 83.3%, range 50-100%) and mean recall rate was 16.3 (median 14.4%, range 3.8-42.4%). In all, 44 radiologists (58.7%) passed the test. On average 1.4 of 6 cancers with minimal signs were correctly identified. According to readers' experience (at least 5 years in mammographic activity, at least 3 years in screening mammography, at least 10,000 total mammograms read, at least 5,000 per year) radiologists were classified as expert (13) or not (62): no difference in test performance was observed between the two groups. The only significant association occurred for years of mammographic activity and sensitivity. DISCUSSION AND CONCLUSIONS: Test results suggest the need for proper training of radiologists prior to involvement in a screening program. Seeding proficiency tests with cancers with minimal signs was of no benefit as far as evaluation is concerned.

Depressive symptoms as measured by the CDI in a population of northern Italian children.

The aim of this study was to evaluate some Children's Depression Inventory (CDI) psychometric properties and the prevalence of depressive symptoms in an unselected Italian sample of two hundred and eighty-four children aged 8 years. The CDI internal consistency was adequate (Cronbach's alpha:.80). The mean and standard deviation of CDI and the percentage of children at risk of depression (10.6%) in this sample are consistent with the figures reported by other studies carried out in northern Europe and North America. There were differences in gender and socioeconomic level in that boys scored higher than girls, and in the lower socioeconomic level there were more children at risk of depression. Ten items best discriminated children at risk for depression with 94% of correct classification. Most of these items consisted of observable signs. It is suggested that the CDI has noteworthy consistency across samples of relatively different cultures, that it can reliably be employed in the assessment of young children, and that observable signs outnumber internalizing symptoms of depression among children at risk

Effect of a single dose of ibuprofen lysinate before embryo transfer on pregnancy rates in cows.

Embryo implantation is a critical step in both cows and humans. The use of ibuprofen lysinate to enhance implantation has been investigated in cattle with the specific aim of improving pregnancy rates after embryo transfer. In this study, heifers (n = 100) were assigned randomly to one of two groups: one group was treated i.m. with 5 mg ibuprofen lysinate kg(-1) body weight 1 h before embryo transfer and a control group received vehicle only. A single embryo was transferred into each recipient cow. There was a significant difference in the number of pregnancies after embryo transfer between cows in the treated (41 of 50; 82%) and control (28 of 50; 56%) groups (P < 0.05). These data indicate that ibuprofen lysinate may be an effective adjunctive treatment for assisted reproduction in cattle. Further studies are needed to clarify whether this effect is associated with the reduction of cyclooxygenase enzyme isoforms during embryo transfer or whether other mechanisms are involved.

Mammographically detected in situ lobular carcinomas of the breast.

We present ten cases of mammographically detected lobular carcinoma in situ (LCIS), involving a single area of variable size (up to a quadrant) in seven cases and the entire gland in three cases. Histologically, calcifications were associated with necrotic central areas within the in situ carcinomatous foci. Multiple foci of LCIS were observed in all five cases in which mastectomy had been performed. Cytologically, the lesions were characterized by a solid proliferation of round noncohesive cells with nuclei of intermediate size. Immunocytochemically, all cases were E-cadherin and p53 negative, and c-ErbB-2, GCDFP-15 and estrogen receptor positive. The proliferation index, evaluated with Ki67, was in the low range. Four cases were associated with foci of infiltrating lobular carcinoma (ILC). These findings contradict the commonly held opinion that LCIS is not mammographically detectable because of its lack of necrosis and calcification. This study documents the existence of a variant of LCIS exhibiting the mammographic features and central necrosis classically associated with ductal carcinoma in situ (DCIS), while retaining the spatial distribution, cytological composition and immunocytochemical features of lobular carcinoma.