Evaluation of colon cancer prognostic factors by CT and MRI: an up-to-date review.

Colorectal cancer (CRC) is a significant global health concern. Prognostication of CRC traditionally relies on the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging classifications, yet clinical outcomes often vary independently of stage. Despite similarities, rectal and colon cancers are distinct in their diagnostic methodologies and treatments, with MRI and CT scans primarily used for staging rectal and colon cancers, respectively. This paper examines the challenges in accurately assessing prognostic factors of colon cancer such as primary tumor extramural extension, retroperitoneal surgical margin (RSM) involvement, extramural vessel invasion (EMVI), and lymph node metastases through preoperative CT and MRI. It highlights the importance of these factors in risk stratification, treatment decisions, and surgical planning for colon cancer patients. Advancements in imaging techniques are crucial for improving clinical management and optimizing patient outcomes, underscoring the necessity for ongoing research to refine diagnostic methods and incorporate novel findings into practice.

Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

Long term testing of Microbial Fuel Cells: Comparison of different anode materials.

This paper focuses on the long term operation and testing of three Microbial Fuel Cells (MFC) having three different anode materials: commercial carbon felt (C-FELT), polyaniline-deposited carbon felt (C-PANI) and carbon-coated Berl saddles (C-SADDLES). A mixed consortium from seawater was used as inoculum and acetate was used as substrate. Tests were conducted for four months under 1000Ω external load. The maximum power generation was obtained by C-SADDLES (102mWm(-2)) followed by C-FELT and C-PANI, respectively. A similar trend was obtained with the evaluation of electrical energy produced: C-SADDLES (2222J), C-PANI (2183J) and C-FELT (2114J). However, the performance of C-PANI decreased over time, most evidently due to degradation or deactivation of deposited polyaniline by the microorganisms' activity. These results provide evidence that the three-dimensional structure, C-SADDLES, offers excellent biocompatibility, high specific surface area, high conductivity and most importantly these properties are maintained for a long period of time.

Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study.

BACKGROUND: A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis. PATIENTS AND METHODS: A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy. RESULTS: Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments. CONCLUSIONS: In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity. CLINICALTRIALSGOV NUMBER: NCT00869310.

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.

Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents.

Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n=54,837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P=1.12 × 10(-)(7)), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.

The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays 'ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted 'patient-specific' therapies.

Acid pre-treatment of sewage anaerobic sludge to increase hydrogen producing bacteria HPB: effectiveness and reproducibility.

The present study is aimed to test the effectiveness and the reproducibility of the acid pre-treatment of sewage sludge to suppress the methanogenic bacteria activity, in order to increase the hydrogen forming bacteria activity, mainly Clostridium species. The treated sludge has been tested on glucose reach medium under mesophilic conditions (35 degrees C), in batch mode to quantify the biological fermentative hydrogen production. In the whole series of experiments, the main components of biogas are hydrogen (52-60%) and carbon dioxide (40-48%); no methane and hydrogen sulphide were present in it. The rate of biogas production reached a maximum of 75 ml/lh. An overall mean hydrogen conversion efficiency was 11.20% on the assumption of maximum of 3 mol H2/mol glucose. Clostridium spp. multiplied ten times after 10 h of fermentation and over that thousand times at the end of fermentation.

Variation of the genetic expression pattern after exposure to estradiol-17beta and 4-nonylphenol in male zebrafish (Danio rerio).

There is much concern about the increasing presence in the environment of synthetic chemicals that are able to disrupt the endocrine system. Among these compounds, 4-nonylphenol (4-NP) is one of the most studied xenoestrogens, due to its widespread accumulation in water sediment and consequent presence in fatty acid of aquatic organisms. Here, we have used a zebrafish microarray representing 16,399 genes to study the effects of 4-NP and estradiol-17beta (E2) in adult male zebrafish in order to elucidate the mechanism of action of 4-NP compared with that of E2. The microarray results showed that both 4-NP and E2 induced a strong expression of vitellogenin (VTG), the sex related precursor of the yolk proteins in oviparous vertebrates. Both treatments induced elevated protein turnover upregulating genes involved in proteolysis and those that are constituents of the ribosome. Many genes regulated by 4-NP and E2 are involved in energy metabolism, oxidative stress defense mechanisms, xenobiotic metabolism, and lipid metabolism. A different pattern of expression in the two treatments was found for genes involved in oxidative stress, since E2 seems to induce the mechanism of detoxification, while 4-NP seems to inhibit this protective mechanism of the cell. Overall, these findings demonstrate that the microarray approach can contribute significantly to the understanding of expression patterns induced by E2 and 4-NP in male zebrafish. The results also demonstrate that 4-NP is able to act through an alternative pattern to that of estradiol-17beta, modulating the expression of the same genes in a different manner.

Partial cloning of CB1 cDNA and CB1 mRNA changes in stress responses in the Solea solea.

Endogenous cannabinoids, through the CB1 receptor, are involved in the control of several functions including stress responses. The aim of this study was to investigate the presence of cannabinoid receptor CB1 in the sole ovary by partial cloning of brain CB1 cDNA; in a stress paradigm of disturbance by handling, which consisted in catching, netting and hand-sorting, changes of CB1 mRNA were related with those of proopiomelanocortin (POMC) mRNA; the trend and timing of stress responses and adaptation were monitored by measuring plasma cortisol levels. We characterized two forms of CB1-like receptor, termed CB1A and CB1B. The two sole CB1 (both 799bp) share 76% identity in their cDNAs, and the deduced amino acid sequences are 80% identical. The handling stress induced a sustained increase in plasma cortisol levels 1h after the handling began and decreased to low levels 12h after initiation of handling, showing the same trend of ovarian POMC mRNA expression. In addition, while CB1A mRNA did not show any significant changes during handling stress, significantly lower levels of CB1B mRNA were found in stressed fish 1h after the beginning of handling, with CB1 expression increased 24h after stress induction, both in the ovary and brain. It can be concluded that endocannabinoid system is involved in the modulation of adaptive responses to environmental conditions.

Quantitative estimation of uncertainty in human risk analysis.

This paper is aimed to candidate the use of an ISO standard procedure (Guide to the Expression of Uncertainty in Measurement, GUM) for quantitative evaluation of uncertainty in Human Risk estimation under chronic exposure to a hazardous chemical compound. Risk was evaluated by using the usual methodologies: the deterministic reasonable maximum exposure (RME) and the statistical Monte Carlo method; in both cases the procedures to evaluate the uncertainty on risk values are detailed. The paper put in evidence that the procedure is able to single out the variables that contribute mostly to the uncertainty. The obtained results show that the application of GUM procedure is easy and straightforward to estimate the uncertainty value on the results of risk estimation. The procedure is applied to a real case concerning the ingestion of milk contaminated by dioxins in a northern part of Italy; the risk value resulted to be over the minimal threshold of 10(-6) with 20-80% confidence.

Changes of gonadal CB1 cannabinoid receptor mRNA in the gilthead seabream, Sparus aurata, during sex reversal.

Two cannabinoid receptor-like genes (CB1-like), named CB1A and CB1B, have been isolated in teleost fish, specifically in the puffer fish, Fugu rubripes. However, information on the physiological roles, such as the control of reproduction and development in fish is still scarce. Therefore, the aim of the present study was to investigate the presence of CB1-like mRNA in the gonads of a marine teleost species, the gilthead seabream, Sparus aurata, a hermaphrodite species in which the gonadal tissues first develop as testes, and then as functional ovary. We isolated an 890 bp fragment (GenBank accession number ); that corresponded to the open reading frame of the teleost CB1 receptor gene, encoding for the central portion of the protein, which was aligned with the other bony fish sequence. Using "in situ" hybridization, CB1-like mRNA was localized in both mature and sex-reversing gonads, and relative changes in CB1-like expression levels were detected through semi-quantitative RT-PCR. In the mature testis and in the testicular part of the sex-reversing gonad, CB1 expression levels were found to be much higher compared to the ovarian portion. This suggests that the CB1 signaling is likely involved in the process of testicular regression of the S. aurata, but its actual role has yet to be determined.

Proopiomelanocortin gene expression and beta-endorphin localization in the pituitary, testis, and epididymis of stallion.

Proopiomelanocortin (POMC) is a precursor protein that contains the sequences of several bioactive peptides including adrenocorticotropin (ACTH), beta-endorphin (beta-EP), and melanocyte-stimulating-hormone (MSH). POMC is synthesized in the pituitary gland, brain, and many peripheral tissues. Immunoreactive POMC-derived peptides as well as POMC-like mRNA have been evidenced in several nonpituitary tissues, thus suggesting that POMC is actively synthesized by these tissues. The present study was aimed at evaluating if also in the case of stallion POMC-derived peptide, beta-EP, is produced locally in the testis, thus playing effects in a paracrine/autocrine fashion. To investigate this hypothesis the POMC gene expression was analyzed using 3' RACE-PCR and Northern Blot approaches in the testis and epididimys of stallion; moreover, immunocytochemical localization for beta-EP was also performed through confocal laser microscopy. The immunofluorescence results showed a positive beta-EP reaction not only in cellular nest of pituitary but also in the testis and genital tract of stallion, which function could be related with sperm mobility. Such role seem not to be no dependent on the peptide synthesized locally, because the molecular biology approach demonstrated the presence of POMC transcript in the pituitary only. In fact the Northern Blot analysis showed the presence of a single POMC transcript in the pituitary while no signal was detected in the testis and epididimys. The same results were obtained by applied 3' RACE-PCR analysis. In conclusion, opioid-derived peptide beta-EP is present in the genital tract of stallion, but is not locally produced as in other mammalian, and nonmammalian models; its possible biological function at testicular level could be linked to a long-loop feed-back mechanisms.

Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-beta estradiol and nonylphenol.

Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17beta and different concentrations (10(-6) and 10(-7) M) of 4-nonylphenol (4-NP) on the expression of liver ERbeta-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17beta) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good "sentinel" species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10(-6) and 10(-7) M) of 4-nonylphenol (4-NP), or 10(-7) M of estradiol-17beta. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 degrees C; the gonads were fixed, then frozen and stored at -70 degrees C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 degrees C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17beta and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17beta plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ERbeta-1 mRNA in the liver, demonstrating that both estradiol-17beta and 4-NP modulate the vitellogenin rate through interaction with the ERbeta-1 subtype. The present study also suggests that 4-NP at the concentration of 10(-6) M bioaccumulates in the liver.

Improving information to Italian cancer patients: results of a randomized study.

BACKGROUND: It has been widely shown that the provision of adequate levels of information to patients does have a positive effect on quality of life by reducing anxiety and depression levels. The aim of this study was to show how Italian cancer patients rate the information they are given and whether the use of booklets and videotapes can improve their quality of life. PATIENTS AND METHODS: Cancer patients aged between 18 and 80 years who were about to receive their first chemotherapy course were randomized to fill in questionnaires on perceived quality of information, level of psychological distress, perceived severity and curability of the disease, and quality of life. The results were evaluated by means of statistical analyses. RESULTS: Out of 328 consecutive patients enrolled in 21 cancer centers, 86-93% considered the booklets either "very useful" or "useful". The videotape was regarded as "quite" or "much" more complete than the booklets (87%). According to 81%/87% of patients, the information that had been given had improved their knowledge of the disease/chemotherapy either "a lot" or "enough". CONCLUSIONS: The information patients receive from the oncologist was rated the highest, as long as they were devoted enough time. Booklets and videotapes can partially overcome the lack of oral information given by medical doctors. A better informed patient does help the oncologist save time.

Development of vascular endothelial growth factor receptor (VEGFR) kinase inhibitors as anti-angiogenic agents in cancer therapy.

Among the known angiogenic growth factors and cytokines implicated in the modulation of normal and pathological angiogenesis, the VEGF family (VEGF-A, VEGF-B, VEGF-C, VEGF-D) and their corresponding receptor tyrosine kinases [VEGFR-1 (Flt-1), VEGFR-2 (Flk-1, KDR), and VEGFR-3 (Flt-4)] play a paramount and indispensable role in regulating the multiple facets of the angiogenic and lymphangiogenic processes, as well as the induction of vascular permeability and inflammation. The receptor VEGFR-2/KDR is the principal one through which VEGFs exert their mitogenic, chemotactic, and vascular permeabilizing effects on the host vasculature. Increased expression of VEGFs by tumor cells and VEGFR-2/KDR and VEGFR-1/Flt-1 by the tumor-associated vasculature are a hallmark of a variety of human and rodent tumors in vivo and correlates with tumor growth rate, micro-vessel density/proliferation, tumor metastatic potential, and poorer patient prognosis in a variety of malignancies. Approaches to disrupting the VEGF/VEGFR signaling cascade range from biological agents (soluble receptors, anti-VEGF and anti-VEGFR-2 antibodies, and VEGF transcription inhibitors) to small molecule ATP competitive VEGFR inhibitors. Examples from this latter class that are currently in clinical development include compounds from distinct chemical classes such as: indolin-2-ones, anilinoquinazolines, anilinophthalazines, isothiazoles, indolo- and indenocarbazoles. The structure activity relationships, biochemical and pharmacological profile of optimized representatives from each of these classes constitute the subject matter of this review.

Dermoscopic diagnosis by a trained clinician vs. a clinician with minimal dermoscopy training vs. computer-aided diagnosis of 341 pigmented skin lesions: a comparative study.

BACKGROUND: In the last few years digital dermoscopy has been introduced as an additional tool to improve the clinical diagnosis of pigmented skin lesions. OBJECTIVE: To evaluate the validity of digital dermoscopy by comparing the diagnoses of a dermatologist experienced in dermoscopy (5 years of experience) with those of a clinician with minimal training in this field, and then comparing these results with those obtained using computer-aided diagnoses. METHODS: Three hundred and forty-one pigmented melanocytic and non-melanocytic skin lesions were included. All lesions were surgically excised and histopathologically examined. Digital dermoscopic images of all lesions were framed and analysed using software based on a trained artificial neural network. Cohen's kappa statistic was calculated to assess the validity with regard to the correct diagnoses of melanoma and non-melanoma. RESULTS: Sensitivity was high for the experienced dermatologist and the computer (92%) and lower for the inexperienced clinician (69%). Specificity of the diagnosis by the experienced dermatologist was higher (99%) than that of the inexperienced clinician (94%) and the computer assessment (74%). Notably, computer analysis gave a higher number of false positives (26%) compared with the experienced dermatologist (0.6%) and the inexperienced clinician (5.5%). CONCLUSIONS: Our results indicate that analysis either by a trained dermatologist or an artificial neural network-trained computer can improve the diagnostic accuracy of melanoma compared with that of an inexperienced clinician and that the computer diagnosis might represent a useful tool for the screening of melanoma, particularly at centres not experienced in dermoscopy.

Human cholecystokinin-A receptor is not an oncofetal protein.

The CCK-A (cholecystokinin-A) receptor is selectively expressed by human pancreatic adenocarcinomas, suggesting a possible role in pancreatic tumorigenesis. In animals, pancreatic CCK receptor expression varies during ontogeny and neoplastic transformation. This study examined the temporal expression of CCK receptors in human fetal, postnatal, and adult pancreas to determine whether the appearance of CCK-A receptors in pancreatic adenocarcinomas reflected oncofetal antigen or pancreatic neoantigen expression. Messenger ribonucleic acid (mRNA) was isolated from six paraffin-embedded normal pancreatic autopsy specimens ranging in age from 17 weeks postfertilization through 26 days following full-term delivery, and samples of adult human tissues, including pancreas and pancreatic adenocarcinoma. Using reverse transcription-polymerase chain reactions, CCK-B receptor mRNA was expressed in all specimens of normal fetal and postnatal human pancreas, adult pancreas, and pancreatic adenocarcinomas. CCK-A receptor mRNA was selectively expressed only in pancreatic adenocarcinomas. These data suggest that selective CCK-A receptor expression in pancreatic adenocarcinomas reflects neoantigen expression in humans.

Macro approach and fuzzy modeling of entrapped biocatalyst.

The interactions between a strain of Saccharomyces cerevisiae and an alginate matrix are investigated to ascertain the main factors affecting the bioreaction evolution. During the tests several parameters (glucose, ethanol, calcium ion and biomass concentration, pH, and alginate bed diameter) were evaluated, coupled with microscopic investigation inside the beads to determine the spatial biomass distribution. A detailed analysis of macro parameters and a correlation among them are proposed using a fuzzy algorithm. A global two-step fuzzy model results in which biomass distribution inside the beads is represented as a hidden parameter.