Synthesis and biophysical characteristics of riboflavin/HSA protein system on silver nanoparticles.

Novel l­Arginine­Dextran70 based-silver nanoparticles (SNPs) (SNPsArg), functionalized with Riboflavin (RF) and Human Serum Albumin (HSA) were characterized by UV-Vis absorption, Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), fluorescence and circular dichroism spectroscopy, chemiluminescence and Neutral red assays. TEM analysis showed the formed faceted particles, large clumps/fused aggregates, nano-featured with the mean particle size of 41.60 nm. Chemiluminescence and Neutral red assays for in vitro antioxidant and cytotoxic activities of the SNPsArg/RF/HSA systems have been studied. It was pointed out that SNPsArg functionalized with RF and HSA resulted in a bio-nanosystem which leads to a high activity against oxygen free radicals, altered viability, morphology, apoptotic bodies and decreased cell density of L929 fibroblast cells. Results are relevant for understanding the redox properties of RF in the case of biological applications and especially for RF containing drugs.

Complexation of ß-cyclodextrin with dual molecular probes bearing fluorescent and paramagnetic moieties linked by short polyether chains.

Electron paramagnetic resonance (EPR) and fluorescence spectroscopies provide molecular-level insights on the interaction of paramagnetic and fluorescent species with the microenvironment. A series of dual molecular probes bearing fluorescent and paramagnetic moieties linked by flexible short polyether chains have been synthesized. These new molecular probes open the possibility to investigate various multi-component systems such as host-guest systems, polymeric micelles, gels and protein solutions by using EPR and fluorescence spectroscopies concertedly. The EPR and fluorescence spectra of these compounds show that the dependence of the rotational correlation time and fluorescence quantum yield on the chain length of the linker is not linear, due to the flexibility of the polyether linker. The quenching effect of the nitroxide moiety on the fluorescence intensity of the pyrene group varies with the linker length and flexibility. The interaction of these dual molecular probes with ß-cyclodextrin, in solution and in polymeric gels, was evaluated and demonstrated by analysis of EPR and fluorescence spectra.

Postnatal Treatment in Antenatally Diagnosed Meconium Peritonitis.

Meconium peritonitis is a rare prenatal disease with an increased rate of morbidity and mortality in the neonatal period. Distinctive features revealed by prenatal and postnatal ultrasoundmay be present: abdominal calcifications, ascites, polyhydramnios, meconium pseudocyst, echogenic mass and dilated bowel or intestinal obstruction. Establishing clear postnatal treatment and prognosis is difficult because of the heterogeneity of the results obtained by ultrasound. The aim of the study is to determine how prenatal diagnosis of meconium peritonitis is associated with perinatal management and further evolution. Clinical results are different depending on the presence of antenatal diagnosis of meconium peritonitis and its form, which can be mild or severe. Surgical treatment and management of meconium peritonitis depend on the clinical presentation of the newborn. Meconium peritonitis diagnosed prenatally differs from that of the newborn, not only concerning the mortality rates but also through reduced morbidity and overall better prognosis.

Pancreaticojejunostomy - Risk Anastomosis after Cephalic Pancreaticoduodenectomy.

INTRODUCTION: The authors bring to attention pancreaticojejunalanastomosis (PJA) performed after cephalic pancreaticoduodenectomy(CPD). This type of anastomosis is renowned forits high risk of complications. Among these complications, pancreatic fistula (PF) is distinguishable due to a significant frequency, averaging 10%. It is perhaps the most unsafe type of anastomosis in digestive surgery, due to its pancreatic partnership. Performing a sealed APJ can be considered a great achievement: a digestive lumen is set in contact with a brittleparenchymal structure, centred by a delicate excretory channel, difficult to anastomose in itself. MATERIAL AND METHODS: We studied two distinct groups of patients undergoing CPD. A first group - 58 cases operated on between 1967 and 1983, and the second one - 70 cases operated on between 1984 - 2013. In all cases we performed PJA; by in-continuity loop technique in the first group, and with separate loop in the second group. In the second group we used a variant own technique that does not allow anastomotic loss of pancreatic fluid. Thus, a decline in the incidence of PF from 20% to 8% was obtained, the final percentage corresponding to group two. Of the 8% of patients with PF losses were recorded strictly at pancreatic level, with no bile or food contamination. Stenting was recorded for biliary- and pancreaticojejunal anastomoses in group two. DISCUSSIONS: The percentage of PF after CPD did not show anynotable revival when comparing the 1980s period to the present. Also, mortality due to FP is approaching 40%, adaunting figure. The multitude of technical options for restoring bowel movement after CPD, over 80 procedures, further confirms the lack of safety and trust in relation to PJA.The authors bring forward several surgical gestures addressing PJA, gestures capable of providing an 8% frequency of PF,percentage which we consider to be reasonable. CONCLUSIONS: The authors consider PJA stenting mandatory.Placing an isolated PJA on the short branch of the "Y", separate from the biliary and food flow, prevents the formation of a complex fistula. The proposed technique does not require a"duct - to - mucosa" type or "telescoping" type pancreaticojejunalanastomosis.

Clinical and Paraclinical Criteria of Patient Selection for the Non-operative Treatment in Completely Responsive Rectal Cancer (after Neoadjuvant Radiochemotherapy).

INTRODUCTION: Neoadjuvant radiotherapy is included in the treatment protocols for rectal tumors in stages = T3. The use of neoadjuvant radiotherapy allowed the limit of surgical oncologic safety margin to decrease with 1-2 cm and the abdominoperineal resection to be able to be performed in tumors situated at 4 cm from the anal verge. This modification of the treatment strategy increased the use of low, ultra low and colo-anal anastomoses. GOAL: Through the analysis of these types of anastomoses and of the disadvantages of the abdomino-perineal resection, we aimed at performing a study on the patients which responded completely to radiotherapy by taking into account the criteria of oncologic safety and the sparing of the patients from surgical complications. MATERIAL AND METHOD: We performed a retrospective study on 171 patients with rectal cancer treated in the 1st Clinic of Surgery from the Bucharest Oncology Institute between October 2007 and December 2013. RESULTS: 141 patients received radiotherapy, out of which 9 responded completely. 5 of those 9 were not operated on and after variable clinical and paraclinical follow up (2-6 years),they did not present with local recurrence. CONCLUSIONS: Not performing surgery in the patients with rectal cancer with a complete response to radiotherapy is a good solution and must be taken after a correct information of the patient about rectal surgery with the condition of strictly observing the selection criteria of the patients.

Morbidity after Ultra Low Anterior Resection of the Rectum.

Anterior resections of the rectum, used as an alternative to amputation of the rectum, are performed more and more frequently, being presently indicated for neoplasms located ata distance of 7 to 4 cm from the anus. Complications of low and ultra low anterior resections are not at all negligible, and local neoplastic recurrence rate is significantly higher than after amputation of the rectum. However, literature data recommends low and ultra low anterior rectal resections, even if sometimes the method indications are pushed to the limit or the interventions are performed at the patient's request, in order to avoid permanent colostomy. The authors of this article aim to outline a true picture of the changes caused by anterior resections of the rectum, low and ultra low, so that, without denying the merits of these resections, the entire postoperative pathology that occurs in these patients is depicted and understood. Ultra low rectal resections, up to 3-4 cm from the anus, bring important morphological and functional changes to the act of defecation and to anal continence. These changes in colo-anal bowel movement have a much higher incidence than postoperative genitourinary disorders. Another important aspect emerging from the present study is related to the increased incidence of anastomotic disunity, stenosis and various degrees of incontinence, complications that often can only be solved by completion of rectum amputation and permanent colostomy. In addition, the functional outcomes of these ultra low resections are not always at the level expected by the patient. Also, in terms of surgical performance, the higher share of specific complications of the procedure raises questions with regard to the technique. For all these reasons the authors consider it necessary to review the lower limit to which an anterior rectal resection can descend.

"Difficult" Colorectal Polyps - Therapeutic Approach.

INTRODUCTION: Endoscopic polypectomy is the gold standard in the treatment of colorectal polyps. The importance of polypectomy rests primarily on the fact that polyp-type lesions present a high risk of malignant degeneration, colorectal polyps being able, if left unattended therapeutically, to generate a colorectal cancer (CRC) - a lesion with a far more negative prognosis. Although preferable, endoscopic polypectomy of colorectal polyps is not always possible, multiple factors generating difficulties in performing this therapeutic measure. MATERIAL AND METHOD: We performed a retrospective study in the First Surgical Clinic of the "Prof. Dr. Alexandu Trestioreanu" Bucharest Oncology Institute, spanning a period of 3 years (2008-2011), in which time 224 patients were diagnosed by colonoscopy with colorectal polyps, of whom 222 patients benefited from endoscopic polypectomy. The aim of the study was to identify "difficult" polyps and to identify the criteria for endoscopic surgery versus classic surgery as a therapeutic indication. RESULTS: Presence of "difficult" polyps was observed in 37.56% of the patients diagnosed with colorectal polyps. In over 88% of cases endoscopic polypectomy was possible, and for the remaining patients classic surgery was the therapeutic solution opted for. CONCLUSIONS: Presence of "difficult" polyps generates inconveniences in performing endoscopic polypectomy, increasing the risk of postoperative complication occurrence, as well as the duration of the operation. If the criteria for characterizing polyps as "difficult" are relatively well-established, the choice between endoscopic and classic surgery as a therapeutic measure is left at the free will of the operating surgeon, with the exception of situations in which classic surgery is resorted to for oncological reasons.

The configuration of biomolecular markers in cancer of the uterine cervix. Personalized therapy. Monitoring and prognosis.

INTRODUCTION: The paper deals with the diagnosis of some aggressive forms of uterine cervix cancers, resistant to radio chemotherapy, using biomolecular markers.For this study, the destruction of tumours in stages II-IIIBis carried out by hyperthermia induced by different sources of energy. The aimed targets are toembed a quick and simple technique of haemostas isused in bleeding uterine cervix tumours associated with acute an aemiain the treatment protocols and to identify biomolecular criteria revealing tumour aggressiveness and treatment response. METHOD: The proposed method consists in radio frequency ablation (RFA) applied touterine cervix bleeding tumours with acute secondary anaemia. Studying 16 patients displaying aggressive cancer forms resistant to radio chemotherapy treated by the above mentioned method, we assessed that the commonly present markers: Ki67, p53 and Bcl-2, may be a substantial indication of such cases. Aggressiveness and treatment resistance was defined based on clinical and paraclinical investigations. RESULTS: RFA haemostasis achieved in approximately 20 m inproved the efficiency of this method. A secondary important effect was local tumour volume decrease, resulting in the improvement of radio-chemotherapy responsiveness. CONCLUSIONS: Once an aggressive and radio-chemotherapy resistant cancer is diagnosed,the quantitative, qualitative and associative presence of the biomolecular markers mentioned herein before, could influence the personalised treatment attitude (radiofrequency, neoadjuvant chemotherapy), which onthe long term, may increase patient survival and life quality improvement.

Return to sports after autogenous osteochondral mosaicplasty of the femoral condyles: 25 cases at a mean follow-up of 9 years.

INTRODUCTION: Autogenous osteochondral mosaicplasty is the most common cartilage restoration technique in standard clinical practice. The purpose of this study was to evaluate the return to sports 9 years after mosaicplasty of the femoral condyles. HYPOTHESIS: The long-term results of an osteochondral autograft show that patients can regain their pre-injury activity level. MATERIAL AND METHODS: This study is based on a series of 25 patients with a mean age of 28.9 years (range, 16-44 years) who had stage 3 or 4 chondral lesions of the femoral condyles (according to the ICRS or ICRS-OCD scores). The origin of the lesion was osteochondritis dissecans (13 knees), osteochondral fracture sequelae (ten knees), or aseptic osteonecrosis (two knees). The average size of the lesion was 2.11 ± 0.9 cm(2). Ten patients (40%) had an associated procedure during the osteochondral autograft. The patients were assessed clinically (IKDC and Lysholm-Tegner scores) and radiographically by a reviewer independent of the team of operators. RESULTS: All patients were re-examined at a mean follow-up of 9 years (range, 6-15 years), with 84% satisfied or very satisfied with the procedure. The average IKDC was 74.5 ± 18.5 points. The average Lysholm score was 87.3 ± 11.6 points. The average Tegner score ranged from 6.35 ± 1.53 points prior to surgery to 5.60 ± 1.64 points after surgery (P = 0.001). The average loss was 0.64 points for patients whose presurgery Tegner score was greater than or equal to 7 (P = 0.019) and 0.3 points if lower than 7. The radiologic evaluation of 21 patients showed complete osteointegration of the grafts in 90% of cases. CONCLUSION: The results of the femoral condyle mosaic autografts are satisfactory, a mean of 9 years after surgery. The most active patients lowered their activity level while the more sedentary did not have to adapt their lifestyle.

Endometriosis still a challenge.

Endometriosis is a debilitating disease with features of chronic inflammation. Endometriosis appears to be one of the most common benign gynecological proliferations in premenopausal women since it is estimated that 10-15% of reproductive aged women suffer from pelvic endometriosis. The biology of endometriosis is unclear. Despite its prevalence, this disease remains poorly understood and current studies prove that there is no relationship between the extent of the disease and its symptomatology. There is no blood test available for the diagnosis of endometriosis. Up to this point, there is no single very successful option for the treatment of endometriosis. Due to the relatively poor efficacy of hormonal therapy for endometriosis, several other experimental therapies are currently undergoing clinical trial.

Laparoscopic treatment for complicated acute appendicitis in children, junior athletes.

BACKGROUND: We present our experience in the first 20 cases of complicated acute appendicitis in children, junior athletes, managed laparoscopically. MATERIALS AND METHOD: We selected our first 20 patients, aged between 3 and 17 (median age 10), with complicated acute appendicitis treated laparoscopically. We analysed the intra and postoperative complications, operative time, length of hospitalization and their return period to previous training.Four cases were excluded from the study because they were converted to open appendectomy (OA). RESULTS: One case developed a parietal abscess at the place of insertion of the suprapubic trocar and was treated locally.There were no cases with intraabdominal abscesses to require drainage. Fever on the 3rd postoperative day appeared in one patient which required reassessment of the antibiotic treatment. Length of hospitalization was between 4 and 8 days.The athletes resumed their sports activity after 10 - 12 days. CONCLUSION: Complicated acute appendicitis (generalized peritonitis, localized abscess, perforated abscess), was once a contraindication for laparoscopic appendectomy (LA). Today LA is the first choice of surgical treatment for most of the surgeons. Due to the limited number of patients we have operated on laparoscopically up to this present paper we cannot draw a statistically significant conclusion, but the good results are encouraging us to continue using this approach as the first line treatment in children and more over for those who need a rapid return to intense physical activity.

The place of radiofrequency ablation in the multimodal treatment of cervical cancer. Our experience.

INTRODUCTION: Genital cancers benefit from standardized treatment plans which include: surgery and radio chemotherapy.Lately, treatments involving thermal ablations have entered the clinical use, as they destroy the tumors by the use of different energy sources. Our study aims at establishing a precise role of RFA in current treatment protocols of cancer of the uterine cervix. MATERIAL AND METHOD: We performed a 5-year (2008-2013)prospective study in which we analyzed the use of RFA inpatients treated for cancer of the uterine cervix at our clinic.RFA was used, on selective criteria, in bleeding tumors of the uterine cervix in patients with acute secondary anaemia(Hb=7-11g dl). The results revealed the haemostatic role of the method, RFA being the only non surgical method through which one can achieve quick haemostasis (20 min.). 61 patients were clinically observed, with ages between 39 and 73, and the number of procedures performed was 61. CONCLUSION: RFA is useful in the treatment of cancers of the uterine cervix, in all stages of the disease, and it achieves quick haemostasis. RFA can be considered an additional treatment option in neoadjuvant tumor palliation. The method can be associated with surgery and radio chemotherapy. Its assets are low specific morbidity (1,6%) and mortality (0%). We consider that RFA is on its way to an important place in oncology treatment protocols.

Differential diagnosis of abdominal wall defects - omphalocele versus gastroschisis.

A newborn with abdominal wall defect is one of the most dramatic cases in neonatology, but also a challenge for pediatric surgeons. This article describes the fundamental concepts of two major abdominal wall defects - gastroschisis and omphalocele - including options and principles of prenatal and postnatal care. Although these birth defects of the abdominal wall are always grouped together, they are two separate and distinct entities, with many differences in terms of pathology and associated anomalies; this explains the different therapeutic approach and results. For a correct management of the newborn with this anomaly, it is essential to understand the similarities and differences between gastroschisis and omphalocele. This article emphasises the similarities between these two parietal defects, highlighting the differences as well.

Therapeutic approach in locally advanced colon tumours (T4NxM0) - clinical experience in 18 consecutive cases.

INTRODUCTION: Surgery holds a central seat in the treatment of colon cancer, its objective being R0 resection. Chemotherapy and an appropriate oncological follow-up complete the treatment. AIM: To establish an adequate therapeutic conduct in patients with advanced colon tumours, with no hepatic metastases. MATERIAL AND METHOD: retrospective study on a group of 150 patients with colon neoplasm treated in the First Surgery Clinic of the Bucharest Oncology Institute in Bucharest,between 01 01 2008 -01 03 2013. RESULTS: 18 patients presented locally extended colon tumours which required multivisceral resections. Patients with hepatic metastases were excluded from the study. The most frequently affected organs were: the small bowel and the internal genital organs, followed by the urinary bladder, spleen, duodenum and diaphragm muscle. Patients were oncologically followed-up according to current protocols and submitted to chemotherapy.When a maximum response was reached in R2 patients or when recurrence occurred in R0 and R1 patients, surgical intervention was required. When necessary, the operation was performed by multidisciplinary teams. 5 patients died due to local recurrence, disease progression, metastatic disease, and also due to comorbidities. CONCLUSION: Treatment applied by oncological committees and multidisciplinary surgical teams, along with correct oncological follow-up and surgical reintervention when maximum response to chemotherapy was reached in R2 or when recurrences occurred in R0 and R1 patients represents the adequate therapeutic conduct in patients with locally advanced colon tumours.

Surgical treatment in stenosing rectal cancer.

INTRODUCTION: Rectal cancer represents an important health issue, which involves multidisciplinary treatment, posing a major surgical challenge, both in terms of diagnosis and treatment. MATERIAL AND METHOD: Between 2009-2013, we analysed 83 patients with stenosing rectal cancer operated on at the Clinic of General Surgery II of Colentina Clinical Hospital and at the Clinic of General Surgery I of "Prof. Dr. Al. Trestioreanu"€ Oncology Institute, in Bucharest. Gender distribution was: 51 males and 32 females. Average age was 65 years old. The most frequently encountered symptoms were colicky abdominal pain and rectorrhagia. 25 patients presented intestinal occlusion phenomena at admission, the other 58 cases being in subocclusive stage. RESULTS: In occlusive stages: 17 patients presented with resectable tumour, while 8 patients had locally advanced neoplastic forms (€œfrozen pelvis€), left iliac colostomy with tumour biopsy being the chosen approach. In subocclusive stages: 5 cases had unresectable tumours for which left iliac anus with tumour biopsy was performed; 53 cases presented with resectable tumour, for which the Hartmann procedure (12 patients) and left iliac colostomy with tumour biopsy (41 patients) were performed. Depending on the histopathological result, patients were submitted to radio- and chemotherapy.Tumour resection was possible in 70 cases (84.33%), only 34 of these (40.96%) being with radical intent. CONCLUSIONS: Treatment for stenosing rectal cancer is multimodal,represented by surgical approach, radio- and chemotherapy. The rationality behind surgery as a first therapeutic gesture in the given study group was represented by the need to treat occlusive type complications, patients benefitting subsequently from radio- and chemotherapy. The opportunity of a second surgical intervention, with the objective to remove the tumour, was established based on the therapeutic response to radio- and chemotherapy.

Morphological and immunohistochemical criteria of tissue response to radiotherapy in rectal cancer.

AIM: Given the context that rectal tumours respond to a certain degree to radiotherapy, a necessity arises for estimating a tumour's capacity to react to radiation from the very moment of diagnostic biopsy. MATERIAL AND METHODS: We have histologically and immunohistochemically analysed tissues coming from 52 patients with rectal adenocarcinomas. RESULTS: Of the studied parameters, the ones presenting significant variation under radiotherapy in terms of statistics(p 0.05) were: colloid type (p=0.001), EGFR in the tumour(p=0.00045), EGFR in the normal epithelium (p=0.0017),VEGF in the tumour (p=0.0132) and VEGF in the tumour stroma (p=0.030). CONCLUSIONS: Our study follows the same trends as the medical literature we have consulted regarding the variation of EGFR and VEGF with radiotherapy, and the distinct note of our study relies in the observation that normal stroma in case of rectal tumors also reacts to radiotherapy, sometimes more aggressively than the tumor itself, especially in which concerns the nerve and muscle fibers.

Considerations on gastroschisis repair.

BACKGROUND: Although primary closure of the gastroschisis is possible in many cases, there have been various strategies published and materials used to cover the eviscerated bowel when the abdominal wall defect cannot be closed in one step, providing bowel protection and reduction of heat and fluid loss. There have been suggestions of coverage materials such as skin graft, lyophilized dura mater graft, free flap corium and meshed skin graft (1,2). PURPOSE: We highlight an alternative repair method of gastroschisis in those cases where there is a disproportion between the amount of eviscerated organs and the hypoplastic abdominal cavity. If in this case primary closure of the abdominal wall is chosen, the difference in volume can cause a significant increase in intraabdominal pressure. METHOD: In some cases, when complete primary closure was not possible, we used an alternative method to repair the parietal defect using umbilical cord patch. RESULTS: This technique creates a mesothelial surface in contact with the bowel. Remote tracking of these patients showed excellent results. CONCLUSIONS: This technique is easy to apply and very useful for infants with gastroschisis especially when primary closure is not possible. The use of autologous material, in this case as the umbilical cord, has several advantages, including wide availability, a lower rate of infection and significantly reduced costs.

True and false incomplete duplications of the common bile duct and their impact on therapy.

The congenital anomalies of the common bile duct (CBD) represent a real challenge for the surgeon, and not recognizing them may have two consequences: either generate incomplete or incorrect surgical solutions, or, even worse, lead to iatrogenic pathology. The association between the anomalies of the CBD and biliary lithiasis, biliary cancer or other hepatobiliopancreatic pathology may lead to a pre/perioperative diagnosis; frequently, the incertitude persists. We present 2 cases: one with an incomplete duplication of the CBD and the other with a false duplication. We wish to underline the sovereign value of cholangio-MRI with 3 D reconstructions in the diagnosis and description of the anatomy of the biliary ducts, superior, in some cases, to the intraoperative cholangiography or ERCP.

A primary hydatid cyst in the abdominal wall -- case report.

INTRODUCTION: A solitary primary hydatid cyst in the abdominal wall is an exceptional entity, even in countries where the Echinococcus infection has a high rate, being considered an endemic disease. CASE PRESENTATION: We report a case of a 70-year-old Caucasian man who presented to our clinic with a slow-growing painless parietal mass in the abdominal wall, right flank area. The diagnosis of cystic mass was established at the ultrasound exam. There were no findings that could describe a hydatic cyst. The punction at the surgical intervention revealed a "clear, stone liquid like"; due to the high risk of major injury of the abdominal wall, we performed partial resection of the outer cystic wall, proligerous membrane removal and drainage. The patient had an uneventful post-operative recovery. The histopathology confirmed the suspected diagnosis. CONCLUSION: Hydatid cyst should be considered in the differential diagnosis of every abdominal intraparietal cystic mass, especially in regions where the disease is endemic. The best treatment is the total excision of the cyst preserving an intact wall (complete cystectomy). Otherwise, removing the proligerous membrane with partial pericyst's resection (partial pericystectomy) and drainage should be considered.

Giant testicular tumor--a case presentation.

BACKGROUND: Testicular cancer is the most common cancer in men 15 to 35 years old. Histological subtypes are seminoma, non-seminoma and mixed tumours (partly seminoma and partly non-seminoma). Seminomas are more sensitive to radiation therapy and are easier to cure than non-seminomas. The surgical treatment is either orchiectomy, either orchiectomy plus lymph node dissection of the involved ganglia. CASE PRESENTATION: We present the case of a 42-year-old man with scrotal pain, important swelling and erythema admitted into our surgical unit. Clinical exam and ultrasound revealed a testicular augmentation of 6/15 cm. Radical orchiectomy was performed and the patient was further referred to the oncology department. CONCLUSIONS: Even though the common causes of scrotal erythema with local swelling and pain are orchiepididimitis and testicular torsion, a careful examination followed by a precise ultrasound can reveal a developing testicular tumor, which was complicated by inflammation. Moreover, a careful anamnesis hints to the development of a tumor as the patient was operated on for cryptorchidism in childhood. Orchiectomy followed by radiotherapy in seminomas, has a cure rate of 70 to 100%.