The Potential of Brewer's Spent Grain in the Circular Bioeconomy: State of the Art and Future Perspectives.

Brewer's spent grain (BSG) accounts for approximately 85% of the total mass of solid by-products in the brewing industry and represents an important secondary raw material of future biorefineries. Currently, the main application of BSG is limited to the feed and food industry. There is a strong need to develop sustainable pretreatment and fractionation processes to obtain BSG hydrolysates that enable efficient biotransformation into biofuels, biomaterials, or biochemicals. This paper aims to provide a comprehensive insight into the availability of BSG, chemical properties, and current and potential applications juxtaposed with the existing and emerging markets of the pyramid of bio-based products in the context of sustainable and circular bioeconomy. An economic evaluation of BSG for the production of highly valuable products is presented in the context of sustainable and circular bioeconomy targeting the market of Central and Eastern European countries (BIOEAST region).

Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology.

The identification of cancer stem cells (CSCs) as initiators of carcinogenesis has revolutionized the era of cancer research and our perception for the disease treatment options. Additional CSC features, including self-renewal and migratory and invasive capabilities, have further justified these cells as putative diagnostic, prognostic, and therapeutic targets. Given the CSC plasticity, the identification of CSC-related biomarkers has been a serious burden in CSC characterization and therapeutic targeting. Over the past decades, a compelling amount of evidence has demonstrated critical regulatory functions of non-coding RNAs (ncRNAs) on the exclusive features of CSCs. We now know that ncRNAs may interfere with signaling pathways, vital for CSC phenotype maintenance, such as Notch, Wnt, and Hedgehog. Here, we discuss the multifaceted contribution of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as representative ncRNA classes, in sustaining the CSC-like traits, as well as the underlying molecular mechanisms of their action in various CSC types. We further discuss the use of CSC-related ncRNAs as putative biomarkers of high diagnostic, prognostic, and therapeutic value.

Acute coagulopathy in children with multiple trauma: a retrospective study.

BACKGROUND: Acute coagulopathy associated with trauma has been recognized for decades and is a constituent of the "triad of death" together with hypothermia and acidosis. STUDY OBJECTIVE: The aim of this study was to determine to what extent coagulopathy is already established upon emergency department (ED) admission and the association with the severity of injury, impaired outcome, and mortality. METHODS: Ninety-one injured children were admitted to the ED in our hospital. Pediatric Trauma Score (PTS), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were used to estimate injury severity, and organ function was assessed by the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Coagulopathy upon pediatric intensive care unit admission was present in 33 children (39.3%): 21 males and 12 females. PTS ranged from 1 to 12 (mean 8.2) in 51 children without coagulopathy and from -1 to +11 (mean 6.8) in 33 children with coagulopathy (p = 0.087). ISS and GCS ranged from 4 to 57 (mean 28) and from 3 to 11 (mean 7.3), respectively, in the coagulopathy group, whereas in the group without coagulopathy, ISS score ranged from 4 to 41 (mean 20.5; p = 0.08) and GCS from 8 to 15 (mean 12.8; p = 0.01). SOFA ranged from 0 to 10 (mean 3.4) in children without coagulopathy and from 0 to 15 (mean 5.4) in the coagulopathy group (p = 0.002). Among 33 children with coagulopathy, 7 did not survive (21%), all with parenchymal brain damage, whereas all trauma patients without coagulopathy survived (p < 0.001). CONCLUSION: Acute coagulopathy is present on admission to the ED and is associated with injury severity and significantly higher mortality.

Gastrointestinal perforations in neonatal period: experience over 10 years.

AIM: This report describes our experience concerning gastrointestinal perforation due to necrotizing enterocolitis during a 10-year period. METHOD: The cases of 27 gastrointestinal perforations, which were treated in our hospital, were retrospectively reviewed. RESULTS: All patients were neonates and infants up to the age of 2 months. The study population consisted of 16 boys (59.3%) and 11 girls (40.7%). Twenty-one neonates (77.8%) were preterm, and the median gestational age was 28 weeks. Twenty-four cases (88.9%) of perforation underwent laparotomy. The overall mortality was 63%. Seventy-six percent of the preterm neonates and only 16.7% of the full-term neonates died. CONCLUSIONS: Gastrointestinal perforation is still connected with a high mortality rate, with necrotizing enterocolitis being the main cause of death. The neonates who did not undergo surgery all died.

Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma.

Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and ß2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM.

Juvenile granulosa cell tumor arising from intra-abdominal testis in newborn: case report and review of the literature.

In the present case, the neonate presented with a left-sided abdominal mass and an empty left scrotum. Abdominal ultrasonography showed well-defined cystic formation, and laparotomy revealed a tumor arising from an intra-abdominal left testis. The carcinoembryonic antigen and neuron-specific enolase levels were within normal limits, and the serum ß-human chorionic gonadotropin and α-fetoprotein levels were within age-related normal values. The findings from the immunochemistry tests confirmed the diagnosis.

A novel role of peripheral corticotropin-releasing hormone (CRH) on dermal fibroblasts.

Corticotropin-releasing hormone, or factor, (CRH or CRF) exerts important biological effects in multiple peripheral tissues via paracrine/autocrine actions. The aim of our study was to assess the effects of endogenous CRH in the biology of mouse and human skin fibroblasts, the primary cell type involved in wound healing. We show expression of CRH and its receptors in primary fibroblasts, and we demonstrate the functionality of fibroblast CRH receptors by induction of cAMP. Fibroblasts genetically deficient in Crh (Crh-/-) had higher proliferation and migration rates and compromised production of IL-6 and TGF-ß1 compared to the wildtype (Crh+/+) cells. Human primary cultures of foreskin fibroblasts exposed to the CRF(1) antagonist antalarmin recapitulated the findings in the Crh-/- cells, exhibiting altered proliferative and migratory behavior and suppressed production of IL-6. In conclusion, our findings show an important role of fibroblast-expressed CRH in the proliferation, migration, and cytokine production of these cells, processes associated with the skin response to injury. Our data suggest that the immunomodulatory effects of CRH may include an important, albeit not explored yet, role in epidermal tissue remodeling and regeneration and maintenance of tissue homeostasis.

Meckel's diverticulum in paediatric practice on Crete (Greece): a 10-year review.

BACKGROUND: Although Meckel's diverticulum (MD) is the most prevalent congenital abnormality of the gastrointestinal tract, it has varied presentations and often becomes a diagnostic challenge. The purpose of this study was to review the diverse presentations of MD, record the epidemiologic features for Crete and review the detection techniques and the treatment options. PATIENTS AND METHODS: This was a review of the records of all children who underwent surgery for MD in the department of Paediatric Surgery of the University Hospital of Crete (Greece) between January 1999 and January 2009. RESULT: A total of 45 patients (32 male and 13 female) aged 1 to 13 years (median 10 years) with a diagnosis of MD were retrospectively reviewed. The collected data were analysed, looking at age, gender, clinical features, investigations, histopathological findings and surgical interventions. In 25 patients, MD was an incidental finding at laparotomy because of appendicitis. The remaining 20 patients were symptomatic and presented with various clinical features. Nine patients (19.9%) had clinical features of peritonitis; of these, three had perforated MD and six had Meckel's diverticulitis at laparotomy. Four patients were diagnosed with intestinal obstruction. Seven patients (15.5%) presented with lower gastrointestinal bleeding. Ultrasound scans revealed intussusception in three patients, requiring open reduction. The remaining four patients with bleeding per rectum underwent a Meckel's Tc99 scan that showed a positive tracer. CONCLUSION: All patients with MD underwent Meckel's diverticulectomy with appendicectomy. MD has an incidence of approximately 1 to 2% in our population. It is necessary to maintain a high index of suspicion in the diagnosis of MD paediatric age group because it can be easily misdiagnosed.

Outcome study of upper pole heminephroureterectomy in children.

OBJECTIVE: We assessed the role and long-term outcome of upper pole heminephroureterectomy in the treatments of non-functioning upper renal moieties in children with duplex kidneys. METHODS: In a period of 10 years, forty-three patients (male: female ratio 6:37) underwent upper pole heminephroureterectomy; a total of 25 patients were diagnosed prenatally. Imaging modalities included renal and bladder ultrasound in all 43 patients, static 99 m technetium dimercaptosuccinic acid (DMSA) in 21 patients, micturating cystourethrogram in 28 patients, MAG-3 in 13, cystoscopy in 30, IVU in 31 and DTPA, retrograde pyelography, antegrade pyelography in 1 patient. The main presentation was with urinary tract infections. Operation was performed through a combination of anterolateral loin incision plus right or left inguinal incision in 34 patients and high flank incision in 9 patients, for various abnormalities. One patient underwent also initial puncture of a ureterocele. RESULTS: Five patients (12%) had immediate post-operative complications. Thirteen patients (30%) had late post-operative complications. Long-term follow-up revealed no complication in 35 (81%) patients and one (2%) patient had one episode of UTI and intermittent abdominal pain. Three patients (7%) had long-term incontinence. Four patients (9%) had a second procedure performed. CONCLUSION: Based on our experience, it seems that upper pole heminephroureterectomy is the treatment of choice in cases of obstructed upper segments of duplicated kidneys, when the affected segment contributes to less than 10% of the overall renal function.

Small bowel intussusception with pelvic plastron secondary to acute appendicitis in child.

We report an unusual case of a 3-year-old child with appendicitis complicated by ileoileal intussusception. Although acute complicated appendicitis and concurrent ileoileal intussusception represent a possible cause of an acute abdomen, very few cases have been reported in the literature.

Outcome study of lower pole heminephrectomy in children.

OBJECTIVE: This study assessed the role and long-term outcome of lower pole heminephrectomy in the treatments of non-functioning lower renal moieties in children with duplex kidneys. MATERIAL AND METHODS: In a period of 10 years 31 lower pole heminephrectomies were performed in 30 patients with duplex systems. Eight patients were diagnosed prenatally, 24 patients (80%) presented with urinary tract infection and three (10%) with vomiting and failure to thrive, and five patients also had other symptoms. The indication for lower pole heminephroureterectomy was reflux nephropathy in non-functioning lower pole in 28 patients (93%), pelviureteric junction obstruction in one patient (3%) and cystic dysplasia in one patient (3%). The surgical technique used was a combination of anterolateral loin incision plus right or left inguinal incision in 28 patients (90%). RESULTS: The operative course was uneventful, no blood transfusion were required, and no damage to the upper pole moiety or upper pole ureter was observed. Four patients (13%) had immediate postoperative complications and three (10%) had late postoperative complications. Long-term follow-up revealed no complications in 27 patients (90%) and three patients (10%) with increased urinary frequency. CONCLUSIONS: The results indicate that lower pole heminephrectomy is the treatment of choice in cases of non-functioning dilated lower segments of duplicated kidneys. The use of two incisions in this procedure is effective in preventing the need for further surgical treatment secondary to complications of the stump.

Detection of herpes viruses in children with acute appendicitis.

OBJECTIVE: This study aimed to investigate the incidence of herpes simplex virus (HSV) types-1 and -2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6) and human herpes virus 7 (HHV-7) in childhood acute appendicitis. STUDY DESIGN: Polymerase chain reaction (PCR) assays were applied to detect herpes virus DNA in 38 children [11 girls and 27 boys, mean age 9 years (STD+/-2.59), range 6-14 years], who underwent an appendectomy within a 2.5-year period. Appendix, omentum and peripheral blood mononuclear cells (PBMCs) were available from each case. Of the 38 children with acute appendicitis, 20 (52.6%) had advanced (phlegmonous) acute appendicitis and 18 (47.4%) had perforated appendicitis and local peritonitis. Forty-one blood specimens from age-matched healthy children (25 female and 16 male), with clinical manifestations unrelated to viral infections served as negative controls. RESULTS: CMV was the most frequently detected virus (8/38, 21%), followed by HHV-6 (3/38, 7.9%). EBV and HSV-1 were detected, though not in all three different types of tissue specimens tested. None of the samples examined were HSV-2-, VZV- or HHV-7-positive. Of all the specimens, the omentum was the most commonly infected tissue (63.0%) while the appendix and peripheral blood specimens were found to be positive for viral infection in 60.5% and 50% of cases, respectively. The CMV IgG+ antibodies were positive in 54% of the control cases while 86% of the same group presented HHV-6 IgG+ antibodies. CONCLUSION: To the best of our knowledge, this is the first study documenting the presence of herpes virus DNA in children with acute appendicitis, suggesting that possible viral infection or reactivation is associated with childhood appendicitis.

Extravaginal testicular torsion: a clinical entity with unspecified surgical anatomy.

PURPOSE: To review and evaluate the anatomical definitions of perinatal extravaginal torsion (EVT) of the testis. MATERIALS AND METHODS: An extensive review of the literature was made to reveal the prevalent anatomical background predisposing to EVT. Gross appearance of twisted testes obtained during surgery for 14 cases of EVT was used to test the validity of the above theories. RESULTS: The most commonly accepted suggestions describe an EVT within dartos muscle that includes all layers of spermatic cord or an EVT outside parietal layer of tunica vaginalis within internal spermatic fascia. However, both of them were found inadequately documented, while a large volume of controversial data has been accumulated, that raises doubts regarding the validity of such definitions. The gross appearance of twisted testes failed to confirm both an EVT including all layers of the spermatic cord and also an EVT outside tunica vaginalis as possible mechanisms of torsion. CONCLUSION: The anatomical basis of EVT remains unclear and further investigation is required.

Extravaginal testicular torsion: a clinical entity with unspecified surgical anatomy

PURPOSE: To review and evaluate the anatomical definitions of perinatal extravaginal torsion (EVT) of the testis. MATERIALS AND METHODS: An extensive review of the literature was made to reveal the prevalent anatomical background predisposing to EVT. Gross appearance of twisted testes obtained during surgery for 14 cases of EVT was used to test the validity of the above theories. RESULTS: The most commonly accepted suggestions describe an EVT within dartos muscle that includes all layers of spermatic cord or an EVT outside parietal layer of tunica vaginalis within internal spermatic fascia. However, both of them were found inadequately documented, while a large volume of controversial data has been accumulated, that raises doubts regarding the validity of such definitions. The gross appearance of twisted testes failed to confirm both an EVT including all layers of the spermatic cord and also an EVT outside tunica vaginalis as possible mechanisms of torsion. CONCLUSION: The anatomical basis of EVT remains unclear and further investigation is required.

An unusual bladder/cloacal exstrophy with urachal exstrophy.

The authors report a previously unpublished association of bladder exstrophy with cleft lip, exomphalos, Meckel's diverticulum imperforate anus, and a large urachal mass protruding below the umbilicus. The baby underwent surgical repair of the condition and the postoperative recovery was uneventful. None of the theories formulated to explain the embryogenesis of bladder exstrophy can explain these findings. The abnormality is within the bladder exstrophy/cloacal exstrophy spectrum.

Acute epididymitis in Greek children: a 3-year retrospective study.

The aim of the study was to compare historical features, physical examination findings, and testicular color Doppler ultrasound in pediatric patients with epididymitis compared to testicular torsion and torsion of the appendix testes. A retrospective review of the medical records of 66 boys presenting with clinical aspects of acute scrotum over a 3-year period was performed. Sixty-six patients were included in the study (29 with epididymitis, 8 with testicular torsion and 12 with torsion of the appendix testis, 4 with scrotal abscesses, 5 with scrotal swelling, and 1 with inflamed epididymal cyst). The duration of symptoms ranged from 6 h to 4 days with a peak on the second day. Urine cultures and viral testes were negative in all patients. Color Doppler ultrasound was diagnostic for epididymitis in 28 patients (96.6%). Systemic intravenous antibiotics were given in all 29 patients with epididymitis. No patient showed signs of testicular atrophy in the follow-up. The increasing incidence of epididymitis should question the policy of routine exploration of the acute scrotum in children. The history and physical examination cannot reliably identify those boys who can be managed conservatively. Color Doppler ultrasound is a useful adjunct in the evaluation of the acute scrotum when physical findings are equivocal but it can also be misleading.

Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study.

AIM: The complex pathobiology of traumatic brain injury (TBI) offers numerous targets for potential neuroprotective agents. We evaluate the clinical benefit after creatine (Cr) administration in children and adolescents. METHODS: A prospective, randomized, comparative, open- labelled pilot study of the possible neuroprotective effect of Cr was carried out on 39 children and adolescents, aged between 1 and 18 years of age, with TBI. The Cr was administered for 6 months, at a dose of 0.4 g/kg in an oral suspension form every day. For categorical variables, we used the Chi-square test to identify differences between controls and cases. Statistical significance was defined as a p-value <0.05 and not statistically significant if p-value >0.1. RESULTS: The administration of Cr to children and adolescents with TBI improved results in several parameters, including duration of post traumatic amnesia (PTA), duration of intubation, intensive care unit stay. Significant improvement was recorded in the categories of headache (p<0.001), dizziness (p=0.005) and fatigue (p<0.001), aspects in all patients. No side effects were seen due to Cr administration. CONCLUSION: More specific examinations including brain spectroscopy for in vivo evaluation of Cr can be done, in order to draw conclusions for the optimal duration and manner of Cr supply, as well as its possible role for the prevention of TBI complications, in double blind studies.

Exposure of normal human melanocytes to a tumor promoting phorbol ester reverses growth suppression by transforming growth factor beta.

Transforming growth factor-beta (TGF-beta), a potent inhibitor of normal melanocyte growth, does not significantly suppress growth of melanoma cells. The mechanism of melanocyte desensitization to TGF-beta in the transformation process remains largerly unknown. We investigated whether the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) may induce melanocyte resistance to TGF-beta. Cell proliferation and DNA synthesis of normal human melanocytes were strongly inhibited by TGF-beta, whereas in the presence of TPA remained largerly unaffected. The inactive phorbol ester 4alpha-phorbol 12,13 didecanoate did not modify the TGF-beta antiproliferative effect, whereas the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol counteracted TGF-beta effects. Protein kinase C (PKC) is the major cellular receptor of tumor promoting phorbol esters. PKC-alpha expression and phosphorylation were almost completely downregulated under combined treatment with TGF-beta + TPA at 24 and 72 h, as shown by immunoblots. Confocal microscopy demonstrated that TGF-beta-induced nuclear accumulation of PKC-alpha was abolished in the presence of TPA at the same time points. The selective PKC inhibitor Ro-31-8220 weakened the TGF-beta antiproliferative effect. Smads are central mediators for TGF-beta signal transduction. Smad-dependent transcriptional activity was suppressed in TGF-beta-treated melanocytes in the presence of TPA, as well as in ALK5 (constitutively active type I TGF-beta receptor)- or Smad3 + Smad4-transfected melanocytes in the presence of Ro-31-8220. In addition, an antisense oligodeoxynucleotide against PKC-alpha abolished TGF-beta-driven Smad-mediated transcription. These findings show that tumor promoting phorbol esters induce melanocyte resistance to TGF-beta, associated with downregulation of PKC-alpha and suppression of Smad-dependent transcription. This may represent an important mechanism for expansion of melanocytes exposed to PKC-targeting tumor promoters.

Semantics-based information modeling for the health-care administration sector: the citation platform.

An information brokerage environment for effective information structuring, indexing, and retrieval in the health-care administration sector is presented. The system is based on ontology modeling, natural language processing, extensible markup language, semantics analysis, and behavioral description. Semantics-based information acquisition is achieved through the uniform modeling, representation, and handling of domain-specific knowledge, both content-based and procedural. The system has been validated using information located on several repositories in the web and its performance is reported in terms of precision and recall.