[Renal, vascular and urological variations and abnormalities in living kidney donor candidates]. / Variations et anomalies néphrologiques, vasculaires et urologiques chez les candidats au don vivant rénal.

INTRODUCTION: The aim of this study was to determine the prevalence of anatomic variations (renal, vascular and urological) and acquired renal pathologies in living kidney donor candidates (LKDC). METHODS: This is a retrospective study of all LKDC referred to our center between April 2003 and September 2014. Of the 491 LKDC, 189 were initially excluded for medical reasons (n=140) or others reasons (n=49), without undergoing a radiological assessment. In total, 302 had a radiological assessment (angio-CT or MRI) in anticipation of the donation and 226/302 (73.5%) could donate a kidney. RESULTS: One or more anatomical variations and/or acquired abnormalities were observed in 178/302 (58.9%) of the LKDC. The most frequent were arterial variations or abnormalities (multiple arteries, fibrodysplasia, aneurysms, stenosis≥70%) which where observed in 39.3% of the LKDC, followed by the venous abnormalities (27.8%). Kidney stones were observed in 5.6% of the LKDC and the urinary abnormalities (duplication/ureteral bifidity) were found in 3% of the LKDC. No malignant tumour was diagnosed, while 4 benign tumours (1.3%) were identified, and one of them required additional investigations. CONCLUSION: We found a high prevalence of anatomical variations and acquired abnormalities in a population of LKDC. However, these findings resulted in the exclusion of only 4% of the candidates, because they did not contraindicate the donation or, in most of cases, the contralateral kidney could be used. LEVEL OF EVIDENCE: 3.

Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Background: Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine whether plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy. Patients and methods: Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was carried out using a panel targeting 46 coding and non-coding genes frequently altered in HCCs. Results: In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) of the patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) of the patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5 cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) of the cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations. Conclusion: In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

In vivo analysis at the cellular level reveals similar steatosis induction in both hepatitis C virus genotype 1 and 3 infections.

Steatosis is a frequent histological feature of hepatitis C virus (HCV) infection. Cohort studies of patients with chronic hepatitis C identified HCV genotype 3 (HCV GT3) as the prevalent steatotic genotype. Moreover, Huh-7 cells over-expressing HCV GT3 core protein accumulate more triglyceride in larger lipid droplets than cells expressing core proteins of other HCV genotypes. However, little is known about the relationship of steatosis and HCV infection at the cellular level in vivo. In this study, we used highly sensitive multiplex in situ hybridization methodology together with lipid staining to investigate HCV-induced lipid droplet accumulation at the cellular level in liver biopsies. Consistent with previous reports, histological steatosis grades were significantly higher in GT3 compared to GT1 infected livers, but independent of viral load. Using nile red lipid stainings, we observed that the frequency of lipid droplet containing cells was similar in HCV GT1- and HCV GT3-infected livers. Lipid droplet formation preferentially occurred in HCV-infected cells irrespective of the genotype, but was also observed in noninfected cells. These findings demonstrate that the main difference between GT1- and GT3-induced steatosis is the size of lipid droplets, but not the number or relative distribution of lipid droplets in infected vs uninfected hepatocytes.

Should central serous chorioretinopathy be added to the list of ocular side effects of phosphodiesterase 5 inhibitors?

INTRODUCTION: Rare cases of central serous chorioretinopathy (CSC) associated with the intake of sildenafil citrate have been reported, although CSC is not included in the list of phosphodiesterase 5 (PDE5) inhibitor side effects. MATERIALS AND METHODS: We present a review of the literature and 2 cases of CSC in 2 men taking PDE5 inhibitors (vardenafil and tadalafil) for erectile dysfunction. In both cases chorioretinopathy appeared after intake of the inhibitor, resolved once the latter was discontinued, reappeared when the inhibitor was restarted and resolved once again after the inhibitor had been discontinued for the second time. DISCUSSION: PDE5 inhibitors used for male erectile dysfunction have been associated with ocular side effects including lid edema, hyposphagma, photophobia, mydriasis, dyschromatopsia, and nonarteritic anterior ischemic optic neuropathy. CSC was previously described in patients taking sildenafil citrate. Very recently, a case of CSC after tadalafil intake was reported. The relevant literature is reviewed and possible pathophysiologic mechanisms are discussed. CONCLUSION: The 2 presented cases of CSC after intake of vardenafil or tadalafil with positive dechallenge, rechallenge and second dechallenge reactions provide important arguments for considering CSC as a rare PDE5 inhibitor class-specific side effect.

How to read a next-generation sequencing report-what oncologists need to know.

Next-generation sequencing (NGS) of tumor cell-derived DNA/RNA to screen for targetable genomic alterations is now widely available and has become part of routine practice in oncology. NGS testing strategies depend on cancer type, disease stage and the impact of results on treatment selection. The European Society for Medical Oncology (ESMO) has recently published recommendations for the use of NGS in patients with advanced cancer. We complement the ESMO recommendations with a practical review of how oncologists should read and interpret NGS reports. A concise and straightforward NGS report contains details of the tumor sample, the technology used and highlights not only the most important and potentially actionable results, but also other pathogenic alterations detected. Variants of unknown significance should also be listed. Interpretation of NGS reports should be a joint effort between molecular pathologists, tumor biologists and clinicians. Rather than relying and acting on the information provided by the NGS report, oncologists need to obtain a basic level of understanding to read and interpret NGS results. Comprehensive annotated databases are available for clinicians to review the information detailed in the NGS report. Molecular tumor boards do not only stimulate debate and exchange, but may also help to interpret challenging reports and to ensure continuing medical education.

Parental education and youth suicidal behaviours: a systematic review and meta-analysis.

AIMS: Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations. METHODS: We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0-18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity. RESULTS: We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04-1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98-1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10-1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54-0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05-1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77-1.08). CONCLUSIONS: The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.

Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study.

BACKGROUND: Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients. AIM: To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients. METHODS: Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function. FINDINGS: Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79). CONCLUSION: SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.

R-Ras interacts with filamin a to maintain endothelial barrier function.

The molecular mechanisms regulating vascular barrier integrity remain incompletely elucidated. We have previously reported an association between the GTPase R-Ras and repeat 3 of Filamin A (FLNa). Loss of FLNa has been linked to increased vascular permeability. We sought to determine whether FLNa's association with R-Ras affects endothelial barrier function. We report that in endothelial cells endogenous R-Ras interacts with endogenous FLNa as determined by co-immunoprecipitations and pulldowns with the FLNa-GST fusion protein repeats 1-10. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In these cells FLNa and R-Ras co-localize at the plasma membrane. Knockdown of R-Ras and/or FLNa by siRNA promotes vascular permeability, as determined by TransEndothelial Electrical Resistance and FITC-dextran transwell assays. Re-expression of FLNa restored endothelial barrier function in cells lacking FLNa whereas re-expression of FLNaΔ3 did not. Immunostaining for VE-Cadherin in cells with knocked down R-Ras and FLNa demonstrated a disorganization of VE-Cadherin at adherens junctions. Loss of R-Ras and FLNa or blocking R-Ras function via GGTI-2133, a selective R-Ras inhibitor, induced vascular permeability and increased phosphorylation of VE-Cadherin (Y731) and Src (Y416). Expression of dominant negative R-Ras promoted vascular permeability that was blocked by the Src inhibitor PP2. These findings demonstrate that maintaining endothelial barrier function is dependent upon active R-Ras and association between R-Ras and FLNa and that loss of this interaction promotes VE-Cadherin phosphorylation and changes in downstream effectors that lead to endothelial leakiness.

Bone mineral density in Egyptian adolescents and adults with short stature: results of a national survey.

Little is known about bone mass acquisition among stunted adolescents who did not achieve their growth in height. A national survey was made of bone mineral density among stunted adolescents and adults. A multistage stratified random sample of 2500 families (8476 adolescents and their parents) was selected from 6 governorates in different geographical areas of Egypt. Clinical history, anthropometry and measurement of bone mineral density using dual energy X-ray absorptiometry was done. Mean T-scores were significantly lower among both adults and adolescents with short stature compared with those of normal height. The predictors of bone status among adolescent boys were age, body mass index (BMI), height attained (z-score) and maternal T-score and for girls were BMI, age at menarche, paternal T-score and z-score. Stunted adolescents suffered from low bone mass density and low stature adults suffered a high prevalence of osteoporosis.

[Melanoma: a new therapeutic era]. / Mélanome: une nouvette ère thérapeutique.

Melanoma is the cancer with the fastest incidence increase in Switzerland. 30% of the cases arise before the age of 50 years. Once metastatic, the median survival under current systemic therapies is about 8 months, with less than 5% of patients alive at 5 years. Many efforts in the understanding of cellular biology, intracellular signaling pathways, as well as the role of cellular immunity have been made in the recent years. This has resulted in the development of novel and very promising therapies. In this review, we will cover the results obtained with targeted therapies such as "tyrosin kinase inhibitors" (TKI), as well as those obtained with a monoclonal antibody directed against the CTLA-4 receptor of lymphocytes.

[EUROCRINE®: adrenal surgery 2015-2019- surprising initial results]. / EUROCRINE®: Nebennierenoperationen 2015 bis 2019 ­ überraschende erste Ergebnisse.

BACKGROUND: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries-or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)-and to assess the adherence to current international treatment guidelines. METHODS: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. RESULTS: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. CONCLUSION: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.

The role of spectral-domain optical coherence tomography in the diagnosis of retinal angiomatous proliferation.

BACKGROUND: We present the findings of spectral-domain optical coherence tomography (OCT) in 8 patients with retinal angiomatous proliferation. HISTORY AND SIGNS: Eight patients with a known history of age-related macular degeneration presented with a recent decrease of visual acuity in one eye. On fundus examination, all patients showed an elevated macular lesion associated with intra- or subretinal hemorrhage and retinal hard exudates. Fluorescein and indocyanine-green (ICG) angiography, together with spectral-domain OCT (Optopol Copernicus SOCT), were performed. THERAPY AND OUTCOME: Fluorescein angiography showed early hyperfluorescence with late leakage in all cases. A serous pigment epithelium detachment was present in 6 cases. ICG angiography showed a hot spot in the macular area. The OCT showed a serous pigment epithelium detachment in 6 cases and intraretinal cysts in all cases. The line crossing the ICG visible hot spot showed a greatly hyperreflective intraretinal lesion located at various depths inside the retina. CONCLUSIONS: Spectral-domain OCT is a useful complementary tool to confirm the diagnosis of retinal angiomatous proliferation. Its high resolution and speed enables accurate localization of the angiomatous lesion.

Update on yesterday's dose-Use of delivery log-files for daily adaptive proton therapy (DAPT).

In daily adaptive proton therapy (DAPT), the treatment plan is re-optimized on a daily basis. It is a straightforward idea to incorporate information from the previous deliveries during the optimization to refine this daily proton delivery. A feedback signal was used to correct for delivery errors and errors from an inaccurate dose calculation used for plan optimization. This feedback signal consisted of a dose distribution calculated with a Monte Carlo algorithm and was based on the spot delivery information from the previous deliveries in the form of log-files. We therefore called the method Update On Yesterday's Dose (UYD). The UYD method was first tested with a simulated DAPT treatment and second with dose measurements using an anthropomorphic phantom. For both, the simulations and the measurements, a better agreement between the delivered and the intended dose distribution could be observed using UYD. Gamma pass rates (1%/1 mm) increased from around 75% to above 90%, when applying the closed-loop correction for the simulations, as well as the measurements. For a DAPT treatment, positioning errors or anatomical changes are incorporated during the optimization and therefore are less dominant in the overall dose uncertainty. Hence, the relevance of algorithm or delivery machine errors even increases compared to standard therapy. The closed-loop process described here is a method to correct for these errors, and potentially further improve DAPT.

Laparoscopic resection of an adrenal oncocytic neoplasm: Report of a case and review of the literature.

INTRODUCTION: Oncocytic adrenal neoplasms are rare and mostly benign lesions. Available literature supports indication for a surgical resection, but criteria to predict aggressive behavior are unreliable, thus making decision of surgical approach (laparotomy versus laparoscopy), and extent of resection, difficult to define. PRESENTATION OF CASE: This is the case of a 46-year-old male, with an incidental finding of a 10 cm asymptomatic tumor in the left adrenal gland identified by MRI, performed in the setting of the initial assessment of liver steatosis. Adrenal hormone levels were in the normal range, thus, a CT-guided needle biopsy was performed and showed an adrenocortical oncocytic neoplasm. A laparoscopic left adrenalectomy was performed sparing the adjacent left kidney. Histological examination of the resected tumor showed a 10 cm oncocytic adrenocortical neoplasm of uncertain malignant potential with negative resection margins. A follow-up MRI was scheduled at six months after surgery, and no recurrence was found. CONCLUSIONS: Although rare, oncocytic neoplasms should be included in the differential diagnosis of adrenal "incidentalomas". Determination of their malignant potential is difficult in the preoperatory setting. Final diagnosis is based on histological analysis of the whole surgical specimen. Laparoscopic complete excision with negative resection margins is feasible and safe.

Hypnosis and superficial cervical anesthesia for total thyroidectomy in a high-risk patient - A case report.

INTRODUCTION: Total thyroidectomy can be challenging in high-risk patients. Local cervical anesthesia with sedation is an alternative to general anesthesia. CASE PRESENTATION: A 33-year old male patient with cyanotic congenital heart disease due to unrepaired tricuspid atresia type Ic and associated pulmonary arterial hypertension presented with tachycardic atrial fibrillation and amiodarone-induced thyrotoxicosis resulting in recurrent hemodynamic instability. Because of difficulties controlling the thyrotoxic state, the indication for total thyroidectomy was established. Total thyroidectomy was subsequently performed using local anesthesia combined using a hypnosis-analgesia technique instead of intravenous sedation. The intervention and the post-operative course were uneventful. DISCUSSION: A well-established therapist-patient relationship is crucial for a successful induction of hypnosis. Patient motivation and expectations are equally important for a successful implementation of this approach. CONCLUSION: We conclude that hypnosis combined with local anesthesia provides an effective alternative in selected patients with very high anesthesiological risk.

A novel laminin E8 cell adhesion site required for lung alveolar formation in vitro.

Basement membrane-adherent type II alveolar cells isolated from lung assemble into lumen-containing cellular spheres which retain the correct polarity and thereby approximate the earliest fetal stage of alveolar morphogenesis. The molecular basis of this process, determined in initial experiments to be attributable mainly to the large heterotrimeric glycoprotein laminin, was probed with laminin proteolytic fragments, antibodies, and synthetic peptides. The carboxy-terminal fragment E8, but not equimolar amounts of fragment P1, blocked alveolar formation. To pursue this observation, we used several anti-E8 antibodies and identified one, prepared against A chain residues 2179-2198 ("SN-peptide") from the first loop of the G domain, as inhibitory. These results were confirmed by use of SN-peptide alone and further defined by trypsin digestion of SN-peptide to the sequence SINNNR. This conserved site promoted divalent cation dependent adhesion of both type II alveolar and HT1080 cells, was inhibitable with equimolar amounts of fragment E8 but not P1, and derives from a form of laminin present in fetal alveolar basement membranes. These studies point to an important novel cell adhesion site in the laminin E8 region with a key role in lung alveolar morphogenesis.

The alpha5beta1 integrin mediates elimination of amyloid-beta peptide and protects against apoptosis.

The amyloid-beta peptide (Abeta) can mediate cell attachment by binding to beta1 integrins through an arg-his-asp sequence. We show here that the alpha5beta1 integrin, a fibronectin receptor, is an efficient binder of Abeta, and mediates cell attachment to nonfibrillar Abeta. Cells engineered to express alpha5beta1 internalized and degraded more added Abeta1-40 than did alpha5beta1-negative control cells. Deposition of an insoluble Abeta1-40 matrix around the alpha5beta1-expressing cells was reduced, and the cells showed less apoptosis than the control cells. Thus, the alpha5beta1 integrin may protect against Abeta deposition and toxicity, which is a course of Alzheimer's disease lesions.

Inhibition of pp125FAK in cultured fibroblasts results in apoptosis.

The tyrosine kinase called pp125FAK is believed to play an important role in integrin-mediated signal transduction. pp125FAK is associated both functionally and spatially with integrins, which are the cell surface receptors for extracellular matrix components. Although the precise function of pp125FAK is not known, two possibilities have been proposed: pp125FAK may regulate the assembly of focal adhesions in spreading or migrating cells, or pp125FAK may participate in a signal transduction cascade to inform the nucleus that the cell is anchored. To test these models in living cells, a peptide representing the focal adhesion kinase (FAK)-binding site of the beta 1 tail was coupled to carrier protein and injected into cultured cells to competitively inhibit the binding of pp125FAK to endogenous integrin, thus inhibiting activation of pp125FAK on a cell-by-cell basis. In addition, an antibody directed against an epitope adjacent to the focal adhesion targeting sequence on pp125FAK was microinjected, as an alternative means of inhibiting pp125FAK activation. It was observed that when rounded cells were injected with either the integrin peptide or the anti-FAK antibody, the cells rapidly began to apoptose, within 4 h after injection. These results indicate that pp125FAK may play a critical role in suppressing apoptosis in fibroblasts.

[Trends in surgery]. / Chirurgie.

More than the number of real novelties, trends and preliminary results characterise the annual development in surgery. The wealth and diversity of topics to be covered require arbitrary choices, therefore not necessarily complete. The constant development of choledocolithiasis management, dominated by minimal invasive technology, treatments of unusual nature of two frequent proctological conditions, fistulae and haemorrhoids, the increasing importance of metabolic bariatric surgery, as well as the strict rules of effective melanoma treatment, represent as many directions in which the operating procedure, although unseen, continue to gain quality and security.

In vitro culture, transformation and genetic fidelity of Milk Thistle.

This review article presents a consolidated explanation and provides a comprehensive description of various studies, carried out on in vitro culture and hairy root cultures of S. marianum which can be consider an alternative source of flavonolignans. To overcome the constrains of conventional propagation of silybum plant, tissue culture and advanced biotechnology proved to be an influential tool that can complement conventional breeding and accelerate silybum development. The present review is focused on biotechnological tools like in vitro culture, hairy root cultures and genetic fidelity of S. marianum which can be a potent tool for production of secondary metabolites from these cultures.