Relation between adenomyosis and elastographic characteristics of the cervix.

STUDY QUESTION: Is there a possible etiologic link between cervical stiffness and adenomyosis? SUMMARY ANSWER: Women with adenomyosis have a stiffer internal cervical os than those without adenomyosis. WHAT IS KNOWN ALREADY: An increased myometrial contractility during menses, leading to breaches in the endometrial basal lamina and subsequent infiltration of endometrial cells into the myometrium, has been proposed as a possible pathogenic mechanism for adenomyosis. Intense menstrual pain has already been shown to be associated with an increased stiffness, at elastography, of the internal cervical os. STUDY DESIGN, SIZE, DURATION: A cross-sectional study on 275 women was performed between 1 February and 31 July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the participants, 103 were and 172 women were not affected by adenomyosis as evaluated by ultrasonography. General and clinical characteristics of the patients were collected. Strain elastography was used to document tissue stiffness at different regions of interest of the cervix, i.e. the internal cervical os, the middle cervical canal, the anterior and the posterior cervical compartment. Tissue stiffness was expressed as a colour score from 0.1 = blue/violet (high stiffness) to 3.0 = red (low stiffness). Simple and multiple logistic regression analyses were used to evaluate the relation between the presence of adenomyosis, as the dependent variable, and independent factors. MAIN RESULTS AND THE ROLE OF CHANCE: Women with adenomyosis had a higher prevalence (P = 0.0001) and intensity (P = 0.0001) of pain during menses, between menses and at intercourse compared to control. The internal cervical os colour score was lower (higher stiffness) in women with adenomyosis (0.55 ± 0.29 versus 0.67 ± 0.26; P = 0.001) and the middle cervical canal/internal cervical os colour score ratio was greater (3.32 ± 4.36 versus 2.59 ± 4.99; P = 0.008), compared to controls. Upon logistic regression modelling (R2 = 0.077), the internal cervical os stiffness was an independent factor related to adenomyosis (odds ratio (OR) 0.220, 95% CI 0.077, 0.627; P = 0.005) along with age (P = 0.005) and the use of gonadal steroid therapies (P = 0.002). We obtained the same results using a different logistic regression model (R2 = 0.069), by substituting the internal cervical os stiffness with the ratio of the middle cervical canal/internal cervical os stiffness (OR 1.157, 95% CI 1.024, 1.309; P = 0.019). LIMITATIONS, REASONS FOR CAUTION: Women did not undergo surgery therefore we have no histological confirmation of the adenomyosis diagnosis. Strain elastography is a semiquantitative analysis and can be conditioned by the force applied by the operator during the analysis. The data were obtained mainly in White women in a single centre. WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first study indicating that women with adenomyosis have an increased stiffness of the internal cervical os. The results indicate that a stiff internal cervical os, as determined by elastography, is a possible contributor to the development of adenomyosis. These findings may have clinical significance and should prompt further investigation. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Ultrasound-based detection of glucocorticoid-induced impairments of muscle mass and structure in Cushing's disease.

PURPOSE: To investigate the glucocorticoid-induced impairments of muscle mass and structure in patients presenting different stages of steroid myopathy progression. METHODS: Thirty-three patients (28 women) affected by active (N = 20) and remitted (N = 13) Cushing's disease were recruited and the following variables were assessed: walking speed, handgrip strength, total body and appendicular muscle mass by bioelectrical impedance analysis (BIA), thickness and echo intensity of lower limb muscles by ultrasonography. RESULTS: The two groups of patients showed comparable values of both handgrip strength [median (interquartile range) values: active disease: 27.4 (7.5) kg vs. remitted disease: 26.4 (9.4) kg; P = 0.58] and walking speed [active disease: 1.0 (0.2) m/s vs. remitted disease: 1.1 (0.3) m/s; P = 0.43]. Also, the thickness of the four muscles and all BIA-derived sarcopenic indices were comparable (P > 0.05 for all comparisons) between the two groups. On the contrary, the echo intensity of vastus lateralis, tibialis anterior (lower portion), and medial gastrocnemius was significantly (P < 0.05 for all comparisons) higher in patients with active disease compared to patients with remitted disease. Finally, significant negative correlations were found in the whole group of patients between muscle echo intensity and muscle function assessments. CONCLUSIONS: We provided preliminary evidence that the ultrasound-derived measurements of muscle thickness and echo intensity can be useful to detect and track the changes of muscle mass and structure in patients with steroid myopathy and we suggest that the combined assessment of muscle mass, strength, and performance should be systematically applied in the routine examination of steroid myopathy patients.

Similar worldwide patterns in the sex pheromone signal and response in the oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae).

The response of Grapholita molesta (Busck) males to three-component sex pheromone blends containing a 100% ratio of the major sex pheromone component, (Z)-8-dodecenyl acetate and a 10% ratio of (Z)-8-dodecenol, but with varying ratios of (E)-8-dodecenyl acetate (0.4, 5.4, 10.4, 30.4, and 100.1% E-blends) was tested with populations in eight stone and pome fruit orchards in Europe, Asia, and North and South America. Traps baited with the 5.4% E-blend caught significantly more males than traps with any other blend with all populations. Significantly more males were caught in traps baited with the 10.4% E-blend than in traps with the remaining blends, except with the 0.4% E-blend in Turkey. Significant differences in male moth catches occurred between the other blends with the 0.4>30.4% E-blend, and the 30.4>100.1% E-blend. Male moth catches with the 100.1% E-blend only differed from the hexane control in Chile. No apparent differences were noted to these blends in populations collected from pome or stone fruits. Flight tunnel assays to synthetic blends with a subset of populations were similar to the field results, but the breadth of the most attractive E-blends was wider. Flight tunnel assays also demonstrated a high level of male-female cross-attraction among field-collected populations. Female gland extracts from field-collected populations did not show any significant variation in their three-component blends. The only exceptions in these assays were that long-term laboratory populations were less responsive and attractive, and produced different blend ratios of the two minor components than recently collected field populations.

Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience.

OBJECTIVES: The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears. METHODS: Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively. RESULTS: LCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%. CONCLUSIONS: LCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.

Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

Evolutionary algorithm-based classifier parameter tuning for automatic ovarian cancer tissue characterization and classification.

PURPOSE: Ovarian cancer is one of the most common gynecological cancers in women. It is difficult to accurately and objectively diagnose benign and malignant ovarian tumors using ultrasound and other tests. Hence, there is an imperative need to develop a computer-aided diagnostic (CAD) system for ovarian tumor classification in order to reduce patient anxiety and the cost of unnecessary biopsies. In this paper, we present an automatic CAD system for the detection of benign and malignant ovarian tumors using advanced image processing and data mining techniques. MATERIALS AND METHODS: In the proposed system, Hu's invariant moments, Gabor transform parameters and entropies are first extracted from the acquired ultrasound images. Significant features are then used to train a probabilistic neural network (PNN) classifier for classifying the images into benign and malignant categories. The model parameter (σ) for which the PNN classifier performs the best is identified using a genetic algorithm (GA). RESULTS: The proposed system was validated using 1300 benign images and 1300 malignant images, obtained from 10 patients with a benign disease and 10 with a malignant disease. We used 23 statistically significant (p < 0.0001) features. By evaluating the classifier using a ten-fold cross-validation technique, we were able to achieve an average classification accuracy of 99.8 %, sensitivity of 99.2 % and specificity of 99.6 % with a σ of 0.264. CONCLUSION: The proposed system is automated and hence is more objective, can be easily deployed in any computer, is fast and accurate and can act as an adjunct tool in helping physicians make a confident call about the nature of the ovarian tumor under evaluation.

MRI assessment of temporomandibular disorders: an approach to diagnostic and therapeutic setting.

AIMS: The aim of this study was to evaluate the relationship between the clinical and the radiological data obtained by magnetic resonance imaging (MRI) in patients with temporomandibular disorder (TMD). METHODOLOGY: The study group included 17 patients with symptoms of TMDs. The radiological assessments before and after therapy was evaluated by MRI; in the clinical analysis, signs and associated symptoms have been assessed. RESULTS: With MRI before therapy, we were able to distinguish the specific type of TMD that each patient had. At the end of the treatment, a general improvement of the clinical status was noticed; MRI, however, showed the permanence of several degrees of condyle-disc incoordination in some patients. CONCLUSIONS: Certainly TMDs can be diagnosed without MRI; nevertheless, MRI gives us the possibility to obtain objective data of the patients concerned. Symptoms recorded during a clinical evaluation cannot be the only terms of diagnosis; MRI provides objective data in the diagnostic and post-therapy phases.

Surgical and functional outcomes of Dorsal Inlay Graft urethroplasty in revision vs primary hypospadias repair in the pediatric age.

INTRODUCTION: Over the years, Dorsal Inlay Graft (DIG) urethroplasty has gained worldwide acceptance for primary hypospadias repair. However, its safety and effectiveness for revision surgery are yet to be proven. OBJECTIVE: The aim of the study is to assess and compare complication rates and functional outcomes of DIG surgery in revision versus primary hypospadias repair. MATERIAL AND METHODS: We carried out a retrospective analysis of data collected from 53 consecutive DIG urethroplasties performed by a single surgeon at our institution. Patients were stratified in two groups - primary repair and redo-urethroplasty. For each group, we recorded standard pre-operative characteristics, surgical technicalities, complication rates and uroflowmetry parameters. RESULTS: Out of 53 DIG urethroplasties, 21 (39.6 %) where primary and 32 (60.4 %) were re-do. As expected, the two groups differed for median age at surgery: 20 months for primary and 68.5 months for revision surgery (p < 0.001). Additionally, all 21 (100 %) primary interventions were performed with a preputial graft, whereas among revision DIG urethroplasties only 2 (6.3 %) where preputial and 30 (93.8 %) were buccal (p < 0.001). Catheterization time (7 vs 8 days, p = 0.155) and postoperative complication rates (14.3 % vs 9.4 %, p = 0.581) were comparable between the primary and revision surgery group, respectively (all p > .05). Forty-two of the 53 patients underwent uroflowmetry during follow-up. Of these, 19 (63 %) patients presented with abnormal uroflowmetry and 11 (37 %) had equivocal parameters with no difference between the two groups. DISCUSSION: Dorsal Inlay Graft urethroplasty has long been known to be safe and effective for primary hypospadias repair. On the other hand, data on dorsal inlay graft urethroplasty as a salvage surgery after primary hypospadias repair failure is scarce. Surprisingly, according to our findings, surgical outcomes and complication rates are comparable between primary and revision hypospadias cases. Additionally, our results in the redo group are absolutely encouraging if compared to those reported in the literature for the same subset of patients. CONCLUSIONS: According to our findings, DIG urethroplasty is a safe and effective option to treat revision hypospadias repair.

Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma.

BACKGROUND: As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies. METHODS: After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing. RESULTS: Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552). CONCLUSIONS: Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials.

HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.

BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease. METHODS: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab. RESULTS: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively). CONCLUSION: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.

Anti-cardiolipin and anti-ß2-glycoprotein I antibodies: normal reference ranges in northwestern Italy.

Laboratory tests for anticardiolipin antibodies (aCL) and anti-ß2glycoprotein I antibodies (a-ß2GPI) face problems common to many autoantibody assays: the lack of a reference standard and the need for each laboratory to assess assay-specific cut-off values. The aims of the study were to evaluate the reference range upper limits (99th percentile) used for aCL and a-ß2GPI in the northwest of Italy and to investigate the analytical performances of these assays with the newly obtained reference ranges. We assayed aCL and a-ß2GPI in 104 serum samples from patients without a history of thrombosis, pregnancy morbidity, tumours, infections and/or autoimmune diseases (30 males and 74 non-pregnant females). We tested all the commercial assays available in our regions (i.e. Orgentec Diagnostika, Aesku Diagnostics and Inova Diagnostics ELISA; CliA Zenit-RA and EliA Phadia Laboratory Systems). A further 30 serum samples, including 10 from healthy subjects, 10 from antiphospholipid syndrome (APS) patients and 10 from septic patients were assessed to investigate the analytical performance of the obtained cut-off limits. Reference range upper limits obtained with the commercial kits differ among assays and from the values reported by the manufacturer. Moreover, normal reference ranges calculated for IgG and IgM aCL differed from the arbitrary selected laboratory classification values suggested in the guidelines of 40 GPL and MPL.

Bioactive injectable hydrogels for on demand molecule/cell delivery and for tissue regeneration in the central nervous system.

Currently there are no potential curative therapies that can improve the central nervous system (CNS) regeneration after traumatic injuries or diseases. Indeed, the regeneration of CNS is greatly impaired by limited drug penetration across the blood brain barrier (BBB), poor drug targeting, deficient progenitor neural cells and limited proliferation of mature neural cells. To overcome these limitations, bioengineered injectable hydrogels in combination with drug and cell therapy have been proposed to mimic the complexity of the CNS microenvironment and architecture. Additionally, to enhance relevant CNS regeneration, proper biophysical and biochemical cues are needed. Recently, great efforts have been devoted to tailor stimuli-responsive hydrogels as novel carrier systems which are able to guide neural tissue regeneration. This review provides an extensive overview on the most promising injectable hydrogels for neural tissue engineering. A special emphasis is made to highlight the ability of these hydrogels to deliver bioactive compounds/cells upon the exposure to internal and external stimuli. Bioactive injectable hydrogels have a broad application in central nervous system's (CNS) regeneration. This review gives an overview of the latest pioneering approaches in CNS recovery using stimuli-responsive hydrogels for several neurodegenerative disorders. STATEMENT OF SIGNIFICANCE: This review summarizes the latest innovations on bioactive injectable hydrogels, focusing on tailoring internal/external stimuli-responsive hydrogels for the new injectable systems design, able to guide neural tissue response. The purpose is to highlight the advantages and the limitations of thermo-responsive, photo responsive, magnetic responsive, electric responsive, ultrasound responsive and enzymes-triggered injectable hydrogels in developing customizable neurotherapies. We believe that this comprehensive review will help in identifying the strengths and gaps in the existing literature and to further support the use of injectable hydrogels in stimulating CNS regeneration.

Muscle fatigue during cross country sprint assessed by activation patterns and electromyographic signals time-frequency analysis.

The aims of this study were as follows: (i) analysis of activation patterns during the spurt of two heats of a cross country skiing sprint with the double poling technique and (ii) quantification of muscle fatigue of the investigated muscles. Eight elite skiers were tested and surface electromyographic signals (EMG) were recorded from seven muscles of the upper and lower limbs. For each subject and each muscle, the activation intervals were calculated for relying on a double-threshold statistical detector and the average rectified value was calculated on each activation interval. The detected activations were processed by a time-frequency algorithm in order to assess the progression of muscle fatigue. The EMG activation patterns and EMG amplitude highlighted no significant difference between the two spurts, despite a generally lower speed in the second spurt. The frequency analysis showed that upper body muscles are the first to be affected by fatigue and that clear signs of muscle fatigue appear right from the first spurt of the sprint simulation (i.e., biceps and triceps brachii) with a decrease in the instantaneous mean frequency. Biceps brachii activations and fatigue demonstrated the involvement of this muscle in propulsion.

Interobserver variability of dynamic MR imaging of the temporomandibular joint.

PURPOSE: This study investigated the interobserver variability of dynamic magnetic resonance (MR) imaging of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Sixty-two patients with internal derangement of the TMJ (124 TMJs) were investigated with a 1.5-T MR imaging system during physiological opening and closing of the mouth. Two readers evaluated independently the quality of the dynamic examination (Q: nondiagnostic, diagnostic, optimal), condylar motion (CM: limited, suboptimal, optimal), condylar orientation (CO: in-plane, through-plane shift), disc visibility and movement (DV: visible, nonvisible; DM: normal, reducing, nonreducing dislocation) and joint effusion (JE: present, absent). For each TMJ, the condylar path was measured by tracing the position of the condyle in the frames of the dynamic acquisition. Agreement between the two readers was assessed with Cohen's Kappa and the Bland-Altman method. RESULTS: Interobserver agreement was almost perfect for Q (nondiagnostic, diagnostic, optimal: 0.8%, 4.9%, 94.3%; κ=1), CM (limited, suboptimal, optimal: 14%, 26.4%, 59.5%; κ=0.84) and DV (visible, nonvisible: 100%, 0%). Substantial agreement was found for DM (normal, reducing, nonreducing: 66.1%, 14.8%, 19.1%; κ=0.64) and JE (present, absent: 41.3%, 58.7%; κ=0.67). Moderate agreement was found for CO (in-plane, through-plane shift: 94.2%, 5.8%; κ=0.41). As for the condylar path, the means of the percentage differences and limits of agreement (LA) were -3% (LA: -34.5%, 28.3%) on the right and -1.2% (LA: -35%, 32.6%) on the left. CONCLUSIONS: In dynamic imaging of the TMJ, qualitative assessment of condyle-disc movement and joint effusion is minimally dependent on the reader's evaluation. Measurement of the condylar pathway shows an interobserver variability of ±30%.

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.

Follow-up of residual shunt after patent foramen ovale closure.

OBJECTIVES: Transesophageal echocardiography (TEE) is usually recommended in the evaluation of the patent foramen ovale (PFO). Our goal is to confirm the efficacy of contrast-enhanced transcranial Doppler (ce-TCD) in detecting residual significant right-to-left shunts (RLS) after PFO percutaneous closure. MATERIALS AND METHODS: Sixty-eight patients with a previous transient ischemic attack, stroke and a large PFO were investigated for residual RLS after percutaneous closure. RESULTS: Assuming TEE as the gold standard, the sensitivity and negative predictive value of ce-TCD was 100%, whereas the specificity was 75.8% and the positive predictive value was 28%. CONCLUSIONS: ce-TCD appears to be the preferable technique to identify subjects with significant residual shunts after percutaneous closure of a PFO. In follow-up, if ce-TCD is negative, no further examination may be necessary; whereas if ce-TCD shows a residual shunt, it is advisable to perform a TEE investigation.

Suitability of buttermilk for fermentation with Lactobacillus helveticus and production of a functional peptide-enriched powder by spray-drying.

AIM: To ferment buttermilk, a low-cost by-product of the manufacture of butter, with a proteolytic strain of Lactobacillus helveticus, to enhance its value by the production of a functional peptide-enriched powder. METHODS AND RESULTS: Buttermilk was fermented with Lact. helveticus 209, a strain chosen for its high proteolytic activity. To enhance the release of peptidic fractions, during fermentation pH was kept at 6 by using NaOH, Ca(CO)(3) or Ca(OH)(2). Cell-free supernatant was recovered by centrifugation, supplemented or not with maltodextrin and spray-dried. The profile of peptidic fractions released was studied by RP-HPLC. The lactose, Na and Ca content was also determined. The powder obtained was administered to BALB/c mice for 5 or 7 consecutive days, resulting in the proliferation of IgA-producing cells in the small intestine mucosa of the animals. CONCLUSIONS: Buttermilk is a suitable substrate for the fermentation with Lact. helveticus 209 and the release of peptide fractions able to be spray-dried and to modulate the gut mucosa in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: A powder enriched with peptides released from buttermilk proteins, with potential applications as a functional food additive, was obtained by spray-drying. A novel use of buttermilk as substrate for lactic fermentation is reported.

Density-based MDCT quantification of lobar lung volumes: a study of inter- and intraobserver reproducibility.

PURPOSE: The authors assessed the reproducibility of multidetector-row computed tomography (MDCT) volumetry of the total and emphysematous parenchyma of pulmonary lobes. MATERIALS AND METHODS: Two observers analyzed 23 MDCT examinations of patients with emphysema during two sessions held 3 months apart. Both lungs and all lobes were delimited by a combination of semiautomated and manual segmentation. Emphysematous parenchyma was obtained by applying density thresholds of -1,024/-950 HU. To assess the reproducibility of total volume (V), volume of emphysema (VE) and emphysema index (EI), intra- and interobserver differences of those measurements were assessed. RESULTS: Total volumetry of the lungs was highly reproducible (intra- and interobserver variability of +/-3.4%). Variability between measurements was slightly greater or emphysema volume and index (EI). Lobar analyses showed large ranges of intra- and interobserver variability (intraobserver V=+/-3.7%-10.6%; VE=+/-17.3%-32.9%; EI=+/-17.8%-34%; interobserver V=+/-13.3%-98.3%; VE=+/-11%-137.6%; EI=+/-28.9%-96.4%). CONCLUSIONS: MDCT quantification of total and emphysematous lung volume and emphysema index is overall reproducible. Quantitative assessment of those parameters performed on single lobes is affected by variability. An improvement of the reproducibility of q-MDCT is expected from the use of advanced methods for lobar segmentation.

Comparison of Histogram-based Textural Features between Cancerous and Normal Prostatic Tissue in Multiparametric Magnetic Resonance Images.

In the last decade, multiparametric magnetic resonance imaging (mpMRI) has been expanding its role in prostate cancer detection and characterization. In this work, 19 patients with clinically significant peripheral zone (PZ) tumours were studied. Tumour masks annotated on the whole-mount histology sections were mapped on T2-weighted (T2w) and diffusion-weighted (DW) sequences. Gray-level histograms of tumoral and normal tissue were compared using six first-order texture features. Multivariate analysis of variance (MANOVA) was used to compare group means. Mean intensity signal of ADC showed the highest showed the highest area under the receiver operator characteristics curve (AUC) equal to 0.85. MANOVA analysis revealed that ADC features allows a better separation between normal and cancerous tissue with respect to T2w features (ADC: P = 0.0003, AUC = 0.86; T2w: P = 0.03, AUC = 0.74). MANOVA proved that the combination of T2-weighted and apparent diffusion coefficient (ADC) map features increased the AUC to 0.88. Histogram-based features extracted from invivo mpMRI can help discriminating significant PZ PCa.