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Composite curves developed from passing individual curves had intercept and slope 95% confidence intervals that were often narrower than without screening and an analysis of covariance test was passed more often. The Excel workbook WLR calculation and acceptance criteria will help laboratories implement draft method C for recreational water analysis in an efficient, cost-effective, and reliable manner.Air pollution epidemiological studies often use outdoor concentrations from central-site monitors as exposure surrogates, which can induce measurement error. The goal of this study was to improve exposure assessments of ambient fine particulate matter (PM2.5), elemental carbon (EC), nitrogen oxides (NOx), and carbon monoxide (CO) for a repeated measurements study with 15 individuals with coronary artery disease in central North Carolina called the Coronary Artery Disease and Environmental Exposure (CADEE) Study. We developed a fine-scale exposure modeling approach to determine five tiers of individual-level exposure metrics for PM2.5, EC, NOx, CO using outdoor concentrations, on-road vehicle emissions, weather, home building characteristics, time-locations, and time-activities. We linked an urban-scale air quality model, residential air exchange rate model, building infiltration model, global positioning system (GPS)-based microenvironment model, and accelerometer-based inhaled ventilation model to determine residential outdoor concentrations (Cout_home, Tier 1), residential indoor concentrations (Cin_home, Tier 2), personal outdoor concentrations (Cout_personal, Tier 3), exposures (E, Tier 4), and inhaled doses (D, Tier 5). We applied the fine-scale exposure model to determine daily 24-h average PM2.5, EC, NOx, CO exposure metrics (Tiers 1-5) for 720 participant-days across the 25 months of CADEE. Daily modeled metrics showed considerable temporal and home-to-home variability of Cout_home and Cin_home (Tiers 1-2) and person-to-person variability of Cout_personal, E, and D (Tiers 3-5). Our study demonstrates the ability to apply an urban-scale air quality model with an individual-level exposure model to determine multiple tiers of exposure metrics for an epidemiological study, in support of improving health risk assessments.Using sequencing analyses of the 16S rRNA gene, we identified Segniliparus rugosus in an 8-year-old child with cystic fibrosis. We describe the difficulties we encountered in identifying this bacterium. To the best of our knowledge, this is the first reported case of S. rugosus in Ecuador.Congenital agenesis of the gall bladder is a very rare ranging from 0.02% to 0.002% in clinical practice. There is complete absence of the gall bladder with normal intra and extra hepatic biliary tree. The exact etiology remains unclear. Low index of suspicion and failure of routine investigations will result in its unexpected discovery during surgery. The condition usually results in diagnostic dilemma both before surgery and intraoperatively. A 25-year-old lady presented with repeated attacks of right side abdominal pain for 1 year. Abdominal examination showed tenderness on palpation in the right hypochonrdium. Abdominal ultrasound showed normal common bile duct with suspicion of small contacted gall bladder. MRCP showed extrahepatic biliary tree and not visualized gall bladder. During diagnostic laparoscopy exploration of the whole peritoneal cavity was performed. The gall bladder was not visualized after complete visualization of biliary anatomy. The appendix was inflamed with multiple adhesions with the bowel. The cecum was high placed in the sub-hepatic region. Laparoscopic appendicectomy was performed. Patients with gall bladder agenesis surprisingly have symptoms similar to cholecystitis, the pain may be attributed to cholangitis, biliary stones, or sphincter of Oddi dysfunction. When the condition diagnosed at operation extensive dissection to identify the gall bladder must be avoided because it may result in biliary injury.Introduction The purpose of this new approach is to develop a method that is less invasive as well as less traumatic and can provide a better exposure/view of the surgical field. Postoperatively, the patient has less pain, short hospital stay and less use of the postoperative pain control medications. As compared to other minimally invasive spine surgeries this approach results in less soft tissue damage, minimal muscle destruction, less retraction and better surgical outcome. Methods In this article authors focus on the new approach that has cost effective benefits as well as short recovery time postoperatively. Results Approach is applicable for severe spinal stenosis as compared to other Minimally Invasive Spine Surgery (MISS) techniques that are only applicable for the mild to moderate stenosis or degenerative processes. This plane is avascular plane so no or less bleeding is anticipated from this procedure. Conclusion The technique facilitates bilateral canal enlargement through unilateral approach and provides accessibility to the contralateral foramen for decompression with perfect exposure and allows instrumentation through the lateral window with no muscle destruction.Ambulatory surgery is an efficient, safe and widely performed procedure; this study would shows the advantages of the ambulatory laparoscopic cholecystectomy procedure from the point of view of patients and the Hospital/National Health System. Materials and Methods Single-center retrospective cohort study including 288 patients who underwent laparoscopic-cholecystectomy at **** from January 2016 to July 2018. Ambulatory LC were compared to well-matched inpatient procedures performed in the same study period. The primary endpoints was the 30-day readmission rate. Secondary endpoints were the discharge rate in the ambulatory group, the post-operative complications rate and cost effectiveness. Results 120/288 (41.7%) patients underwent ambulatory laparoscopic cholecystectomy. Thirty-two (26.7%) patients who underwent ambulatory laparoscopic cholecystectomy had major preoperative comorbidities and 35 (29.2%) had undergone prior abdominal surgery. The readmission rates for ambulatory patients and inpatients were 0.8% and 1.7% (p = 0.56), respectively; 104 (86.7%) ambulatory patients were discharged successfully on the same day. The two groups showed the same post-operative complication rate (p = 0.40). Ambulatory procedures resulted in related cost savings of more than 300% for the hospital and a remarkable financial benefit for the National Italian Healthcare System, accounting for savings exceeding € 27 000 per year. Conclusions Ambulatory laparoscopic cholecystectomy is safe and cost effective. Since a third of ambulatory patients showed comorbidity or previous abdominal surgery, we believe that this procedure may be performed safely in a tertiary HPB centre, even in complex patients.Capnocytophagia canimorsus (C. canimorsus) is a Gram-negative bacilli present in the gingival flora of canine and feline species. It is the second most common cause of infection following dog bites and contact with canine saliva, leading to severe sepsis in immunocompromised patients with no evidence of a breach to the skin. We present the case of a previously healthy 51-year-old male who presented with disseminated intravascular coagulopathy, acute renal failure with widespread haemorrhagic bullae and skin necrosis. He was treated empirically with broad-spectrum antibiotics for sepsis of unknown origin for several days before C. canimorsus infection was identified on blood cultures. Following this, a more detailed social history identified the vital historical detail that the patient owned 7 dogs. His purpura fulminans secondary to sepsis was managed conservatively with regular dressings by the Burns Department. Our experience demonstrates that C. canimorsus should be considered as a causative organism in patients presenting with sepsis of unknown origin after contact with domestic animals and treated with early antibiotic therapy.Introduction This is the first report on near-infrared fluorescent (NIRF) clip-guided gastrectomy. The NIRF clip, ZEOCLIP FS, emits NIRF signals when excited. We hypothesized that preoperative placement of the ZEOCLIP FS near a gastric lesion would allow fluorescence laparoscopic localization of the clip, and hence, the lesion, during surgery. We report this technique in two cases. Case presentation Case 1 An 81-year-old female was diagnosed with early gastric cancer and a pedunculated 4 cm large hyperplastic polyp that had prolapsed into the duodenum, and was scheduled for laparoscopy-assisted distal gastrectomy, due to the potential risk of dissection of the polyp with the duodenal wall. On the day before surgery, ZEOCLIP FS clips were endoscopically placed at the cancer site and the polyp. The locations of the fluorescent clips were confirmed intraoperatively using a full-color fluorescence laparoscope. Case 2 An 81-year-old male was scheduled for laparoscopy-assisted total gastrectomy for gastric cancer under fluorescent clip-guidance. Clip locations could not be confirmed during initial intraoperative observation. However, when the stomach wall was raised using forceps during a second observation attempt, the fluorescent clip locations were confirmed. Discussion In case 1, it was easy to confirm clip location, facilitating complete resection of early gastric cancer without dissecting the polyp. In case 2, the fluorescent clip was located by raising the stomach and adjusting the angle between the stomach wall and the fluorescence laparoscope. Conclusion The positive results of these two cases warrant conducting feasibility studies for use of this method.The incidence of anal cancer has increased during the second half of the 20th century, with an incidence rate over 2.9% greater than in the decade of 1992-2001. Yet, it still constitutes a small percentage, about 4%, of all anorectal tumours. Its risk factors are human papillomavirus infection, a history of sexually transmitted diseases, a history of vulvar or cervical carcinoma, immunosuppression related to human immunodeficiency virus infection or after organ transplantation, haematological or immunological disorders, and smoking. The most frequent symptom is rectal bleeding (45%), followed by anal pain, and sensation of a rectal mass. The diagnosis requires clinical examination, palpation of the inguinal lymph nodes, high resolution anoscopy followed by fine-needle aspiration biopsy or core biopsy. Subsequent histologic diagnosis is necessary, as well as computed tomography or magnetic resonance imaging evaluation of the pelvic lymph nodes. Since 1980, patients with a diagnosis of anal cancer have shown a significant improvement in survival. In Europe during the years 1983-1994, 1-year survival increased from 78% to 81%, and the improvement over 5 years was between 48% and 54%. Prior to 1974, patients with invasive cancer were routinely scheduled for abdominoperineal amputation, after which it was demonstrated that treatment with 5-fluorouracil and radiotherapy associated with mitomycin or capecitabine could be adequate to treat the tumour without surgery. Today, numerous studies have confirmed that combined multimodal treatment is effective and sufficient.Background The Montgomery case in 2015 resulted in a pivotal change in practice, leading to a patient-centric approach for informed consent. Neck of femur (NOF) fractures are associated with a high rates perioperative morbidity and mortality. Using guidelines highlighted by the British Orthopaedic Association we performed a multi-loop audit within our department to assess the adequacy of informed consent for NOF fractures. Methods Two prior cycles had been performed utilising a similar framework. Prior interventions included ward posters, verbal dissemination of information at Junior Doctor's (JD) induction and amendments to the JD handbook. For the latest audit loop, a retrospective analysis of 100 patients was performed. Risk were classified as common, less common, rare and 'other' non-classifiable risks. The adequacy of informed consent was evaluated by assessing the quality and accuracy of documentation in the signed Consent Form-1s for compos mentis patients. Results Infection, bleeding risks, clots and anaesthetic risks were documented in all patients (100%). Areas of improvement included documentation of neurovascular injuries (98%), pain (75%) and altered wound healing (69%). There was no significant change in the documentation of failure of surgery (83%) and neurovascular injuries (98%). Poorly documented risk factors included mortality (21%), prosthetic dislocation (14%) and limb length discrepancy (6%). Conclusion Following the latest cycle, the trust has now approved the use of 2 consent-specific stickers (for arthroplasty or fixation), amendable on a patient-to-patient basis. As part of the multi-loop process, the cycle will be repeated every year, in line with Junior Doctor rotations. Medical professionals have an ethical, moral and legal obligation to ensure they provide all information regarding surgical interventions to aid patients in making an informed decision.Hemoglobinopathies are the most common single gene disorders (monogenic disorders) in the world population. Due to specific position of Iran and the presence of multi-ethnic groups in the country, there are many varieties in the molecular genetics and clinical features of hemoglobinopathies in Iran. Hemoglobinopathies include structural variants, thalassemias, and hereditary persistence of fetal hemoglobin. In this review, we look at the common structural variants in various parts of the country along with their hematological and clinical characteristics. Also, we discuss about the burden of the thalassemias in the country, different types, complications, molecular defects and therapy.Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated intravascular coagulation (DIC). The therapeutic methods of APL contain All Trans Retinoic Acid (ATRA), arsenic trioxide (ATO) or/and chemotherapy. Many studies have been done on APL blood disorders and its treatment. These studies have shown different results. In this systematic article, we tried to review the effect of ATO therapy with or without ATRA and chemotherapy on DIC parameters (D-dimer, Prothrombin Time, Activated Partial Thrombin Time, Platelet count) in APL patients. The result of included studies demonstrated that although ATO can reduce the number of malignant cells in the bone marrow and peripheral blood, it does not have enough potential to attenuate the danger of high score DIC that is usual in APL patients and should be better to be used with other therapeutic methods.Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder presenting with steroid-responsive anemia and diaphyseal dysplasia of long bones. We report a 3-year-old Iranian girl with refractory anemia, splenomegaly and radiologic signs of metadiaphyseal dysplasia in long bones. The diagnosis was established by clinical presentation and X-ray bone survey. The patient was treated with oral prednisolone therapy with considerable improvement in anemia and splenomegaly.Acute Lymphoblastic Leukemia is a very aggressive malignant disorder of lymphoid cells in adults, with recurrence (30 to 60% of the cases) after the initial treatment. Until this moment, there is no gold standard therapy for the treatment of adult patients with acute relapsed/refractory lymphoblastic leukemia. In this case report, we describe two cases of relapsed leukemia one of lymphocytic leukemia B and one of trilineage leukemia, which presented a satisfactory response to treatment with Bortezomib associated with Vincristine, Dexamethasone, and Bendamustine.At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemia patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemia patients. Two successful Fludarabine-based non-myeloablative stem cell transplantation in two Class III β thalassemia patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation. After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemia patients, we concluded that Fludarabine-based non-myeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemia patients.Background A genetic polymorphism of 50 bp insertion/deletion (Ins/Del) (rs 36232792) in the promoter region of the SOD1 was reported to influence the enzyme activity. The present study aimed to evaluate the status of this polymorphism of human peripheral blood cells and its association with SOD enzyme activity in beta-thalassemia major patients. Material and Methods The study was carried out on 200 thalassemia major patients and 200 healthy controls healthy. The SOD1 genotypes were determined using a polymerase chain reaction (PCR)-based method. Serum SOD activity were assessed using SOD assay kit. In-silico analysis was assessed using loss-of-function (LoFtool) (PMID 27563026). Results No association was found between the insertion/deletion (Ins/Del) polymorphism and SOD enzyme activity in thalassemia major patients Conclusion The results of this study indicated that the SOD enzyme activity is not affected by the 50 bp Ins/Del polymorphism of SOD1in thalassemia major patients. Further research with larger sample size and with other genes of antioxidant system is required.Background Acute T lymphoblastic Leukemia (T-ALL) is a highly aggressive hematologic malignancy. Chemotherapy resistance is one of the most important challenges in T-ALL treatment. Alterations in cellular signaling pathways such as Notch1 and PI3K/AKT/mTOR play a role in cell proliferation, survival, and resistance to chemotherapy. Combination of Notch1 and PI3K/AKT/mTOR inhibitors is an interesting and rational strategy in treatment of T-ALL. Interaction of AZD5363 as an inhibitor of PI3k/AKT/mTOR and Compound E as an inhibitor of Notch1 signaling pathway was investigated in a T-ALL pre-clinical model. Materials and Methods T-ALL cell lines included Jurkat, Molt-4, and HPB- ALL cells were treated with AZD5363 and Compound E alone and in combination. Cell viability was determined by MTT assay. Flow cytometry was used to measure apoptosis. Interaction between AZD5363 and Compound E was assessed by Chou-Talalay method. Results Combination treatment with AZD5363 and Compound E decreased cell viability with synergistic effect in all cell lines at 72 hours. Drug combination increased apoptosis even in Jurkat and HPB-ALL cells resistant to Compound E and AZD5363, respectively. Conclusion Combination of AZD5363 with Compound E in T-ALL cell lines exhibited a synergistic effect. Cytotoxicity of drug combination increased in all T-ALL cell lines compared to each as a single drug. Simultaneous inhibition of Notch1 and PI3K/AKT signaling pathways as a possible treatment of T-ALL, provides a basis for future investigations.Background Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. Bone marrow angiogenesis is crucial for pathogenesis of leukemia, and increasing bone marrow Mean Vascular Density (MVD) and level of angiogenesis factors are seen in patients with AML. Higher level of bone marrow MVD is associated with poor prognosis of AML according to previous studies. The present study aimed to compare bone marrow MVD in AML patients and controls and evaluate the relation between bone marrow MVD and number of residual blast cells after AML treatment. Materials and Methods This study is a longitudinal study on AML patients who were admitted to Omid hospital. The bone marrow biopsies of patients with AML and patients with normal diagnosis -as control group- were taken from archives of pathology laboratory. Immunohistochemistry staining was used for all specimens by using thrombomodulin markers for calculating MVD. Flow cytometry findings of AML patients were assessed for percent of minimal residual disease (MRD) after AML treatment in AML patients group. Results In this study, 27 AML patients and 24 healthy individuals with mean age of 40.92±15.13 years were evaluated, of whom 56.86% were male. The mean bone marrow MVD was significantly higher in AML patients than controls. The mean bone marrow MVD was significantly higher in males and there was insignificant reverse correlation between bone marrow MVD and MRD. About 59.3% of AML patients had response to treatment and there was no significant relationship between MVD and response to treatment. Conclusion Bone marrow MVD was higher in AML patients than controls and there was no remarkable relationship between bone marrow MVD and MRD and response to treatment.The present letter to editor is related to "Cui WQ, Wang ST, Pan D, Chang B, Sang LX. Caffeine and its main targets of colorectal cancer. World J Gastrointest Oncol 2020; 12(2) 149-172 [DOI 10.4251/wjgo.v12.i2.149]".Background Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course. Aim To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients. Methods A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014-2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient's demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated. Results Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P less then 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI 2.889-10.429; P less then 0.05). Conclusion LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection.Background Gastric Helicobacter pylori (H. pylori) infection is related to chronic gastritis, gastroduodenal ulcer, and gastric malignancies; whether this infection is related to colorectal polyps and colorectal cancer (CRC), remains debatable. Aim To investigate the relationship between gastric H. pylori infection and the risk of colorectal polyps and CRC. Methods We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis. We also analyzed 304 patients with primary CRC. The characteristics of these patients were compared with those of the control group, which included 2362 patients with the normal intestinal mucosa. All subjects completed a 14C-urea breath test, bidirectional gastrointestinal endoscopy, and a biopsy on the same day. Data on the number, size, location, and pathology of the polyps, the location, and pathology of the CRC, the detection of H. pylori, and the incidence of H. pylori-associated atrophic gastritis or intestinal metaplasia wes that the incidence of gastric H. pylori infection and H. pylori-associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.Background Peritoneal metastasis (PM), arising from gastric cancer (GC), is the most common pattern of synchronous and metachronous dissemination and is generally associated with poor prognosis. New therapeutic modalities are being increasingly employed for such patients. Aim To develop more advanced methods, it becomes necessary to study the results of existing standard treatment methods in patients with PM in order to perform a comparative analysis of the strategies. Methods A retrospective analysis of the efficiency of standard treatment methods (i.e., palliative chemotherapy, palliative gastrectomy, and the best supportive care) was performed on 200 GC patients with synchronous PM. Results The overall survival (OS) rate in 200 GC patients with PM under standard treatment was 5.4 mo. One-year survival occurred in 18.4% of patients. In multivariate analysis, the survival rate was significantly influenced by the following factors Presence of extraperitoneal metastases, and stage of PM according to both the J supportive care (P = 0.0008). Conclusion GC patients with PM are characterized by extremely poor prognoses. Long-term survivors were found in the group with PCI of 1-6 points, and there was no survival difference in groups with PCI 7-12 vs PCI 13+ points. Palliative gastrectomy could prove effective in treating patients with early stage PM. The three standard treatment methods are equally effective for moderate stages of PM. In cases with advanced peritoneal carcinomatosis, a significant increase in prognosis was registered only after treatment with palliative chemotherapy.Background Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer (> T2, N+) before tumour resection in many European guidelines. However, there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours, in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients. Aim To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy, localisation, and age. Methods We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016. The data were evaluated particularly in relation to patient age, tumour site, and perioperative therapy. Results Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. The 5-year survival rates were 40% for patients who received perioperative chemotherapy and 29% for the group without perioperative chemotherapy (P = 0.125). Our patients were on average distinctly older than patients in most of the published randomised controlled trials. Patients elder than 75 years received perioperative chemotherapy far less frequently. Patients with a proximal tumour received perioperative chemotherapy much more often. Conclusion This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer. There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.Background The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment have never been investigated. Aim To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival. Methods All patients with colorectal peritoneal metastases (1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a bi-institutional database (Uppsala and Sydney) were included in the study. Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs non-neutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for disease-free survival were implemented. Results Two hundred and forty-six patients were identified - 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the non-neutropenia group (66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P = 0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02. Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio 0.58, 95% confidence interval 0.36-0.95, P = 0.03. Conclusion 13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity.Background Toll-like receptor-2 (TLR2) is responsible for recognizing Helicobacter pylori (H. pylori) and activating the immune response. Polymorphisms in TLR2 may modulate gastric carcinogenesis. Aim To evaluate whether the TLR2 19216T/C (rs3804099) and TLR2 -196 to -174 ins/del (rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA expression. Methods DNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples [202 gastric cancer (GC), 269 chronic gastritis (CG), and 383 control/healthy (C)] and genotyped by allele-specific PCR or restriction fragment length polymorphism (RFLP)-PCR. Quantitative polymerase chain reaction by TaqMan® assay was used to quantify TLR2 mRNA levels in fresh gastric tissues (48 GC, 36 CG, and 14 C). Results Regarding the TLR2 -196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparog-additive (P = 0.0021)]. TLR2 mRNA levels were significantly increased in the GC group (median RQ = 6.95) compared to the CG group (RQ = 0.84, P less then 0.0001) and to the normal mucosa group (RQ = 1.0). In addition, both H. pylori infection (P less then 0.0001) and the presence of the polymorphic TLR2 -196 to -174del (P = 0.0010) and TLR2 19216 C (P = 0.0004) alleles influenced TLR2 mRNA expression. Conclusion The TLR2 -196 to -174 ins/del and TLR2 19216 T/C polymorphisms are strongly associated with GC. TLR2 mRNA expression levels are upregulated in neoplastic tissues and influenced by both the presence of H. pylori and variant genotypes.Background The integrin β6 gene, which is expressed in epithelial cancer, plays a pivotal role in various aspects of cancer progression. The present research for integrin β6 regulation mainly focuses on the post-transcription and translation related regulation mechanism and its role in tumorigenesis. The mechanisms of how the integrin β6 gene is regulated transcriptionally, and the promoter and transcription factors responsible for basic transcription of integrin β6 gene remain unknown. Aim To clone and characterize the integrin β6 promoter. Methods Software analysis was used to predict the region of integrin β6 promoter. Luciferase reporter plasmids, which contained the integrin β6 promoter, were constructed. Element deletion analysis was performed to identify the location of core promoter and binding sites for transcription factors. Results The regulatory elements for the transcription of the integrin β6 gene were located between -286 and -85 and contained binding sites for transcription factors such as STAT3 and Ets-1. Conclusion For the first time, we found the region of β6 core promoter and demonstrated the binding sites for transcription factors such as Ets-1 and STAT3, which are important for integrin β6 promoter transcription activity. These findings are important for investigating the mechanism of integrin β6 activation in cancer progression.Background Colorectal cancer (CRC) is a worldwide problem, which has been associated with changes in diet and lifestyle pattern. As a result of colonic fermentation of dietary fibres, short chain free fatty acids are generated which activate free fatty acid receptors (FFAR) 2 and 3. FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells. Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis. Aim To understand the role of short chain FFARs in CRC. Methods Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines. We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes, which was validated using quantitative real time polymerase chain reaction. Assays for glucose uptake and cyclic adenosine monophosphate (cAMP) generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown. Fomediated cAMP signalling. Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes. This study paves the way to understand the mechanism of action of short chain FFARs in CRC.Paraseptal emphysema (PSE) is a relatively unexplored emphysema subtype that is usually asymptomatic, but recently associated with interstitial lung abnormalities which are related with clinical outcomes, including mortality. Previous local-based methods for emphysema subtype quantification do not properly characterize PSE. This is in part for their inability to properly capture the global aspect of the disease, as some the PSE lesions can involved large regions along the chest wall. It is our assumption, that path-based approaches are not well-suited to identify this subtype and segmentation is a better paradigm. In this work we propose and introduce the Slice-Recovery network (SR-Net) that leverages 3D contextual information for 2D segmentation of PSE lesions in CT images. For that purpose, a novel convolutional network architecture is presented, which follows an encoding-decoding path that processes a 3D volume to generate a 2D segmentation map. The dataset used for training and testing the method comprised 664 images, coming from 111 CT scans. The results demonstrate the benefit of the proposed approach which incorporate 3D context information to the network and the ability of the proposed method to identify and segment PSE lesions with different sizes even in the presence of other emphysema subtypes in an advanced stage.The presence of ipsilateral aneurysm in the stenosis of the internal carotid artery is determined by computed tomography angiography in 1.8%-3.2% of cases. The literature describes the most varied options for treating this pathology isolated or alternate, and now the method of simultaneous endovascular treatment - carotid stenting and endovascular embolization of aneurysm - is gaining popularity. We presented a clinical case of treatment of 61 women with critical stenosis (90%) and tortuosity of the internal carotid artery in combination with ipsilateral saccular aneurysm of the anterior connecting artery. The uniqueness of this case lies in the fact that a hybrid approach has been applied in the treatment of pathology, not previously described in the literature. The case is highlighting the potential complexity of concomitant vascular cervical and cerebral pathology and the necessity of surgical and endovascular team interactions to choose the appropriate methods of treatment.Pulmonary embolism (PE) is a major cause of morbidity and mortality in the United States and usually occurs secondary to venous thromboembolism. Inferior vena cava (IVC) filters are minimally invasive intravascular devices placed in patients who are at increased risk for venous thromboembolism leading to PE, however, has a contraindication to medical anticoagulation therapy. The longest reported case of a retrievable IVC filter has remained in place and successfully removed in a living patient has been 4753 days (13 years). We present a case of an uneventful, successful IVC removal with a dwell time of 6033 days (16 years).Skull-based neuroendocrine carcinomas are rare tumors with only a few case reports in literature. Here we present an unusual case of primary neuroendocrine carcinoma of the skull in 60-year-old male which was proven on surgical biopsy. The imaging features of this rare tumor along with differential diagnosis are discussed with brief review of the literature.Primary ovarian leiomyoma is a very rare benign mesenchymal tumor arising from the smooth muscle of walls of ovarian blood vessels. It is usually seen between 20 65 years of age. Being asymptomatic in many patients, these are incidentally detected. Ultrasonography and magnetic resonance imaging are preferred modality while imaging these lesions. Hereby we present a case of a 35-year-old female with incidentally detected right ovarian mass lesion which was hypointense on ultrasonography, hypointense on both T1W and T2W images, and on histopathology confirmed as primary ovarian leiomyoma. T1- and T2-weighted hypointensity on MRI with early homogenous postcontrast enhancement help in its diagnosis, though many a time it is difficult to differentiate it from other mesenchymal fibrous tumors such as fibroma and fibrothecoma. Histopathology and immunohistochemistry remain the mainstay in final confirmatory diagnosis. It is important to keep this entity in the differential diagnosis of solid T1 and T2 hypointense lesions of the ovary.Mature cystic teratoma (MCT) is a benign, slow-growing tumor and accounts for approximately 75% of mediastinal germ cell tumors. Patients with MCT are often asymptomatic when the tumors are small. Most of the symptoms are frequently related to compression of the mediastinal structures. We herein describe 3 adult cases of MCT. The patients were a 37-year-old man, a 35-year-old woman, and a 54-year-old woman. They were hospitalized with compression-related symptoms, such as chest pain, dyspnea, and cough. Findings from conventional chest radiograph, computed tomography (CT), magnetic resonance imaging were characterized. Conventional chest radiography still plays a major role in the initial evaluation of MCT, while CT remains the preferred modality for initial cross-sectional imaging evaluation of mediastinal lesions. However, thoracic magnetic resonance imaging provides more detailed and often definitive evaluation of mediastinal masses than CT because of its superior tissue characterization.Pituitary macroadenoma is the most common suprasellar lesion in adults. If symptomatic, it is managed surgically via transsphenoidal resection. Patients commonly present with headache and visual disturbances. If the tumour is large enough, it may have mass effect and patient may present with symptoms of elevated intracranial pressure like severe headache, nausea and vomiting. Functional adenomas may cause endocrine dysfunction. Here, we present a case of pituitary macroadenoma in a young adult female who presented with headache. Initial CT and MRI revealed a pituitary macroadenoma. However, repeat imaging done preoperatively showed complete regression of the lesion and a normal appearing pituitary gland.Chylous ascites is a rare, but highly morbid complication of oncologic resection, often associated with retroperitoneal lymphadenectomy. Conservative measures with total parenteral nutrition or lipid-reduced formulas constitute the initial mainstay therapy, but not without risks and failures. This report describes 2 endolymphatic treatment strategies for iatrogenic chylous ascites following neuroblastoma resection. Lymphatic leaks were identified using intranodal lymphangiography, targeted with cone-beam computed tomographic guidance, and embolized with n-butyl cyanoacrylate. There were no adverse outcomes, with complete resolution of chylous ascites and a mean follow-up of 26 months.The global threat of multiresistant pathogens has to be answered by the development of novel antibiotics. Established antibiotic applications are often based on so-called secondary or specialized metabolites (SMs), identified in large screening approaches. To continue this successful strategy, new sources for bioactive compounds are required, such as the bacterial genera Xenorhabdus or Photorhabdus. In these strains, fabclavines are widely distributed SMs with a broad-spectrum bioactivity. Fabclavines are hybrid SMs derived from nonribosomal peptide synthetases (NRPS), polyunsaturated fatty acid (PUFA), and polyketide synthases (PKS). Selected Xenorhabdus and Photorhabdus mutant strains were generated applying a chemically inducible promoter in front of the suggested fabclavine (fcl) biosynthesis gene cluster (BGC), followed by the analysis of the occurring fabclavines. Subsequently, known and unknown derivatives were identified and confirmed by MALDI-MS and MALDI-MS2 experiments in combination with an optimized sample preparation. This led to a total number of 22 novel fabclavine derivatives in eight strains, increasing the overall number of fabclavines to 32. Together with the identification of fabclavines as major antibiotics in several entomopathogenic strains, our work lays the foundation for the rapid fabclavine identification and dereplication as the basis for future work of this widespread and bioactive SM class.In this review we present relevant and recent applications of porphyrin derivatives as photocatalysts in organic synthesis, involving both single electron transfer (SET) and energy transfer (ET) mechanistic approaches. We demonstrate that these highly conjugated photosensitizers show increasing potential in photocatalysis since they combine both photo- and electrochemical properties which can substitute available metalloorganic photocatalysts. Batch and continuous-flow approaches are presented highlighting the relevance of enabling technologies for the renewal of porphyrin applications in photocatalysis. Finally, the reaction scale in which the methodologies were developed are highlighted since this is an important parameter in the authors' opinion.Two new spiroindolinonaphthoxazine derivatives with an electron-accepting styrylquinolizinium or styrylcoralyne unit, respectively, were synthesized, and the influence of such an arylvinyl substituent on the chemical and photochemical properties of the compounds was investigated. Specifically, these spirooxazines turned out to be resistant towards the photoinduced merocyanine formation, and the irradiation with light mainly led to photodegradation of the substrates. However, it was shown by colorimetric and fluorimetric screening assays as well as by detailed NMR spectroscopic and mass spectrometric studies that the addition of particular metal ions (Cu2+, Fe3+, and to a certain extent Hg2+) initially induced a ring-opening reaction that was irreversibly followed by a fast ring closure-deprotonation-oxidation sequence to give styryl-substituted naphthoxazole derivatives as the products quantitatively. For the quinolizinium-substituted spirooxazine derivative, the formation of the respective oxidation product caused the development of a broad absorption band between 425 nm and 500 nm and a new emission band at λfl = 628 nm, so that it may be employed as a selective chemosensor or chemodosimeter for the colorimetric and fluorimetric detection of Cu2+ and Fe3+.Boomerang-shaped bipyrroles containing donor-acceptor units were obtained through a tandem palladium-mediated reaction consisting of a cyclization step, involving double C-H bond activation, and a double α-oxygenation. The latter reaction can be partly suppressed for the least reactive systems, providing access to α-unsubstituted boomerangs for the first time. These "α-free" systems are highly efficient fluorophores, with emission quantum yields exceeding 80% in toluene. Preliminary measurements show that helicene-like boomerangs may be usable as circularly polarized luminescent materials.For investigations on the biological functions of oligosaccharides and peptidomimetics, new asparagine-based mono- and disaccharides containing glycopeptides were prepared in solution. The applicability of two common peptide coupling reagents, using an orthogonal Fmoc/t-Bu strategy along with acetyl protecting groups for the carbohydrate moiety, was studied. Thus, the prepared libraries of glycopeptides were designed as model systems of cell surfaces for future investigations by combined preparative mass spectroscopy and scanning tunneling microscopy (STM) using soft-landing electrospray beam deposition (ES-IBD), on metal surfaces.A diversity-oriented synthesis (DOS) approach has been used to functionalize 17-ethynyl-17-hydroxysteroids through a one-pot procedure involving a ring-closing enyne metathesis (RCEYM) and a Diels-Alder reaction on the resulting diene, under microwave irradiations. Taking advantage of the propargyl alcohol moiety present on commercially available steroids, this classical strategy was applied to mestranol and lynestrenol, giving a collection of new complex 17-spirosteroids.When conducting a photooxidation reaction, the key question is what is the best amount of photocatalyst to be used in the reaction? This work demonstrates a fast and simple method to calculate a reliable concentration of the photocatalyst that will ensure an efficient reaction. The determination is based on shifting the calculation away from the concentration of the compound to be oxidized to utilizing the limitations on the total light dose that can be delivered to the catalyst. These limitations are defined by the photoflow setup, specifically the channel height and the emission peak of the light source. This method was tested and shown to work well for three catalysts with different absorption properties through using LEDs with emission maxima close to the absorption maximum of each catalyst.Copper catalysis finds applications in various synthetic fields by utilizing the ability of copper to sustain mono- and bielectronic elementary steps. Further to the development of well-defined copper complexes with classical ligands such as phosphines and N-heterocyclic carbenes, a new and fast-expanding area of research is exploring the possibility of a complementing metal-centered reactivity with electronic participation by the coordination sphere. To achieve this electronic flexibility, redox-active ligands can be used to engage in a fruitful "electronic dialogue" with the metal center, and provide additional venues for electron transfer. This review aims to present the latest results in the area of copper-based cooperative catalysis with redox-active ligands.Secondary mitral regurgitation (SMR) is a common occurrence in patients with heart failure with reduced ejection fraction. Moderate-severe or severe SMR is associated with increased mortality and hospitalisations from heart failure. Medical and cardiac resynchronisation therapies have been the only treatments proven to improve prognosis in this patient population. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy (COAPT) and the Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) RCTs evaluated transcatheter mitral valve repair with MitraClip for treatment of SMR in addition to medical therapy and they had divergent results. The COAPT trial demonstrated that a reduction in SMR with MitraClip resulted in reduced mortality and heart failure hospitalisations along with improved symptoms and quality of life in appropriately selected patients. The MITRA-FR trial did not show any benefit from using MitraClip for patients with SMR. This article summarises the differences in these two trials and suggests a contemporary approach to the management of SMR.Background The path for the development of hypersecreting strains of Trichoderma reesei capable of producing industrially relevant enzyme titers remains elusive despite over 70 years of research and industrial utilization. Herein, we describe the rational engineering of the publicly available T. reesei RUT-C30 strain and a customized process for cellulase production based on agroindustrial by-products. Results A CRISPR/Cas9 system was used to introduce six genetic modifications in RUT-C30. Implemented changes included the constitutive expression of a mutated allele of the cellulase master regulator XYR1, the expression of two heterologous enzymes, the β-glucosidase CEL3A from Talaromyces emersonii and the invertase SUC1 from Aspergillus niger, and the deletion of genes encoding the cellulase repressor ACE1 and the extracellular proteases SLP1 and PEP1. These alterations resulted in a remarkable increase of protein secretion rates by RUT-C30 and amended its well described β-glucosidase deficiency while enablines for Trichoderma research on cellulase production.Many complications may ensue coronary bypass surgery. Among these complications, early or late dissection of the ascending aorta is a very rare condition. Successful surgery without life-threatening results can save lives. In this case report, we present a case of aortic dissection due to cross-clamp injury in a patient who underwent coronary artery bypass surgery. A 60-year-old female patient underwent double-vessel aortocoronary bypass surgery due to coronary artery disease. After distal bypasses were performed and the cross-clamp was removed, dissection of the aorta occurred. Consequently, axillary cannulation and ascending aortic replacement with a prosthetic graft were performed via the open technique. The saphenous vein graft was sutured to the aortic prosthetic graft, and cardiopulmonary bypass was terminated after hemodynamic stability was achieved. The patient was discharged on the 10th postoperative day, and she has been followed up for 2 years after surgery without any problems.
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