Intestinal obstruction induced by portal vein thrombosis in a female undergoing oral contraceptive therapy: a case report with comprehensive review.

Introduction: Portal vein thrombosis (PVT) is a rare medical condition that obstructs blood flow in the portal vein, with cirrhosis as a common predisposing factor. However, its association with oral contraceptive pills (OCPs), particularly with progestins, remains inadequately explored. This case report aims to contribute to this understanding, focusing on the rare presentation of PVT-induced intestinal obstruction in a female on prolonged OCP therapy. Case presentation: A 45-year-old female presented with severe abdominal pain, vomiting, and constipation. Diagnosis revealed PVT-induced intestinal obstruction, an exceptionally rare occurrence in the context of prolonged OCP therapy. The patient's symptoms improved with conservative management, including rivaroxaban, highlighting the crucial role of early intervention. Discussion: This case brings attention to the limited literature exploring the link between OCPs and PVT. Despite the generally safe reputation of OCPs, they can induce pro-thrombotic conditions, emphasizing the need for heightened clinical awareness. In this case, the rarity of intestinal obstruction in PVT, compounded by the absence of common risk factors, underscores the diagnostic challenges associated with such presentations. Conclusion: PVT-induced intestinal obstruction in a patient on prolonged OCP therapy is exceptionally rare, emphasizing the necessity for multidisciplinary management. It provides crucial insights into suspecting, identifying, and treating this uncommon complication in non-cirrhotic individuals, contributing to the limited existing literature on the subject.

N-acetyl cysteine turns EPAC activators into potent killers of acute lymphoblastic leukemia cells.

Today, the majority of patients with pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL, hereafter ALL) survive their disease, but many of the survivors suffer from life-limiting late effects of the treatment. ALL develops in the bone marrow, where the cells are exposed to cAMP-generating prostaglandin E2. We have previously identified the cAMP signaling pathway as a putative target for improved efficacy of ALL treatment, based on the ability of cAMP signaling to reduce apoptosis induced by DNA damaging agents. In the present study, we have identified the antioxidant N-acetyl cysteine (NAC) as a powerful modifier of critical events downstream of the cell-permeable cAMP analog 8-(4-chlorophenylthio) adenosine-3', 5'- cyclic monophosphate (8-CPT). Accordingly, we found NAC to turn 8-CPT into a potent killer of ALL cells in vitro both in the presence and absence of DNA damaging treatment. Furthermore, we revealed that NAC in combination with 8-CPT is able to delay the progression of ALL in a xenograft model in NOD-scid IL2Rγnull mice. NAC was shown to rely on the ability of 8-CPT to activate the guanine-nucleotide exchange factor EPAC, and we demonstrated that the ALL cells are killed by apoptosis involving sustained elevated levels of calcium imposed by the combination of the two drugs. Taken together, we propose that 8-CPT in the presence of NAC might be utilized as a novel strategy for treating pediatric ALL patients, and that this powerful combination might be exploited to enhance the therapeutic index of current ALL targeting therapies.

Radical decompression without fusion for L5 radiculopathy due to foraminal stenosis.

Background: The highest incidence of lumbar foraminal stenosis (LFS) occurs in the L5-S1 segment and its anatomical features differ from those of other segments. Few previous reports have exhaustively assessed surgical outcomes after decompression surgery, limiting the materials to patients with LFS at the L5-S1 segment. We aimed to prospectively investigate instability and neurological improvement following our novel surgical technique for LFS at L5-S1, named "radical decompression" of the nerve root. Methods: Patients with foraminal stenosis at L5-S1 who underwent surgery using our technique were prospectively evaluated two years postoperatively. The Japanese Orthopaedic Association (JOA) score and the JOA Back Pain Evaluation Questionnaire (JOABPEQ) were evaluated preoperatively and two years postoperatively. The following radiological parameters at L5-S1 were measured: lateral translation, sagittal translation, the difference in sagittal translation (DST) between flexion and extension, disc wedging angle, lordotic angle, the difference in lordotic angle (DLA) between flexion and extension, and disc height. Pre- and postoperative data were compared using paired t-tests. In addition, the patients were classified into a disc group (Group D) and a non-disc group (Group ND) according to whether a discectomy was performed intraoperatively. Changes in each parameter before and after surgery were compared between the groups. Results: Twenty-eight patients were included in this analysis. The JOA scores improved in all patients. The mean preoperative and two-year postoperative JOA scores were 14.5±3.2 (range, 8-21) and 24.3±3.3 (range, 18-29), respectively (P<0.01). All JOABPEQ categories improved two years postoperatively (P<0.05). None of the patients underwent revision surgery. No significant changes were observed in any of the radiological parameters. No significant differences in the changes in each parameter before and after surgery were found between groups D and ND. Conclusions: Our surgical technique resulted in good neurological recovery and was associated with a low risk of postoperative segmental instability, regardless of additional discectomy.

Targeting caspase pathway by novel N-Me aziridine derivatives for hepatocellular carcinoma drug discovery.

Azaheterocycles are three-membered rings, known as aziridines, that occur naturally and have pharmaceutical applications.These compounds are present as several secondary metabolites produced by plants and microorganisms.Recent studies have demonstrated the effectiveness of aziridine derivatives (N-H/N-Me) as anticancer agents.We synthesized 18 compounds containing an N-Me enone aziridine group, the chemistry of which has been previously published. However, these compounds have drug-likeness properties; therefore, we aimed to demonstrate their drug-like properties using in silico and in vitro investigations.The molecular structures of the compounds were optimized using density functional theory (DFT). The ADMET parameters of the derivatives were calculated using SwissADME and PreADMET. Additionally, these derivatives were evaluated for their ability to bind to caspase-3 and caspase-9 and then subjected to molecular docking. The lead chemical AY128 maintained stable complexes with target proteins during molecular dynamics simulations, as evidenced by the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) parameters. In vitro cytotoxicity and ELISA tests showed that the novel aziridine derivatives, especially AY128, had strong anticancer activity against HepG2 hepatocellular carcinoma cells.Our study suggests that AY128 may be a potential drug candidate for hepatocellular carcinoma through the caspase-3 and caspase-9-dependent apoptotic pathways.Communicated by Ramaswamy H. Sarma.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Postpartum Guillain-Barré syndrome: a case report.

Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the central nervous system presenting as symmetrical, progressive weakness and areflexia. The incidence of GBS is very low during pregnancy, but the risk increases in the postpartum period. The management is done by intravenous immunoglobulin or conservatively. Case Presentation: Case of 27 years female with parity 1, living 1, on postpartum day 20 presented to the emergency department (ED) with weakness over legs and hands since 20 days following emergency lower segment cesarean section for her delivery. The weakness prevailed over the lower extremities and progressed to the upper extremities in 4-5 days, affecting her grip strength and ability to stand alone. No history of prior diarrheal or respiratory illness. Cerebrospinal fluid analysis revealed albuminocytologic dissociation. A nerve conduction study showed in-excitable bilateral radial, median, ulnar, and sural nerves. Intravenous immunoglobulin was administered at the rate of 0.4 g/kg once daily for 5 days. Patient was discharged after 2 weeks with regular physiotherapy follow-up. Conclusion: GBS in the postpartum period is very rare. There must be a high degree of suspicion among physicians for GBS if a pregnant female or a woman during her postpartum period presents with ascending muscle paralysis, even if there is no recent antecedent history of diarrheal episodes or respiratory illness. An early diagnosis with multidisciplinary supportive measures helps improve the prognosis for both the mother and the fetus.

DDX3-mediated miR-34 expression inhibits autophagy and HBV replication in hepatic cells.

HBV entry to the host cells and its successful infection depends on its ability to modulate the host restriction factors. DEAD box RNA helicase, DDX3, is shown to inhibit HBV replication. However, the exact mechanism of inhibition still remains unclear. DDX3 is involved in multitude or RNA metabolism processes including biogenesis of miRNAs. In this study, we sought to determine the mechanism involved in DDX3-mediated HBV inhibition. First, we observed that HBx protein of HBV downregulated DDX3 expression in HBV-infected cells. Overexpression of DDX3 inhibited HBx, HBsAg and total viral load, while its knockdown reversed the result in Hep G2.2.15 cells. Expression of miR-34 was downregulated in HBV-infected cells. Overexpression of pHBV1.3 further confirmed that HBV downregulates miR-34 expression. Consistent with the previous finding that DDX3 is involved in miRNA biogenesis, we observed that expression of miR-34 positively corelated with DDX3 expression. miRNA target prediction tools showed that miR-34 can target autophagy pathway which is hijacked by HBV for the benefit of its own replication. Indeed, transfection with miR-34 oligos downregulated the expression of autophagy marker proteins in HBV-expressing cells. Overexpression of DDX3 in HBV-expressing cells, downregulated expression of autophagy proteins while silencing of DDX3 reversed the results. These results led us to conclude that DDX3 upregulates miR-34 expression and thus inhibits autophagy in HBV-expressing cells while HBx helps HBV evade DDX3-mediated inhibition by downregulating DDX3 expression in HBV-infected cells.

Pulmonary Barotrauma in COVID-19 Patients: Experience From a Secondary Care Hospital in Oman.

Background During the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many patients developed pulmonary barotrauma either self-inflicted or ventilator-induced. In pulmonary barotrauma, air leaks into extra-alveolar tissue resulting in pneumomediastinum, subcutaneous emphysema, pneumothorax, and pneumoperitoneum. Methods After obtaining institutional approval, we retrospectively reviewed data from March 1, 2021, to September 31, 2021. Being a retrospective study, informed consent was not applicable. Patient data were collected from the Al Shifa patient information portal, which is an electronic medical record system available to all hospitals in the Ministry of Health, Oman. After identifying patients with pulmonary barotrauma, the following details were recorded and entered into an Excel sheet (Microsoft Corporation, Albuquerque, New Mexico) and a database was created, which contained the following: age, sex, smoking history, comorbidities, type, location, mode of barotrauma, mode of ventilation, length of intensive care unit (ICU) stay, interventions performed, and overall outcome (survived/deceased). Results A total of 529 patients with COVID-19 pneumonia were admitted from March 2021 to September 2021 to the ICU. Twenty-eight patients developed barotrauma of variable severity and required interventions like the placement of intercostal drains. Out of 28, five patients developed spontaneous barotrauma, 14 patients had barotrauma after initiation of non-invasive ventilation, and nine patients had barotrauma as a result of invasive ventilation. The median number of days in the ICU was 19.5 (interquartile range: 12.5-26.5). Of the 28 patients, eight patients survived and were discharged from the hospital. Conclusion In this single-center, retrospective study at a secondary care hospital in Oman, we described our experience with patients who suffered pulmonary barotrauma during their ICU admission. We have also presented the incidence of spontaneous versus ventilator-induced barotrauma, the length of stay of these patients, the outcomes in terms of survival or death, the need for tracheostomy, secondary infections, and interventions performed as indicated.

Biplane double supported screw fixation for femoral neck fracture in young adults: A prospective cohort study.

Introduction: Achieving accurate anatomic reduction and stable internal fixation is mandatory in the management of femoral neck fractures (FNF) in adults. The spatial configuration and direction of the screws have been reported to provide stability to the fracture. The study's goal is to analyse the clinico-radiological outcome of the newer biplane double-supported screw fixation (BDSF) technique in the Indian cohort. Materials and methods: Patients with isolated FNFs underwent osteo-synthesis by BDSF technique. Radiological outcome was evaluated by time to union and fracture healing on plain radiographs. Clinical outcome was measured using the Harris hip score (HHS) at 1, 3, 6, and 12 months after surgery. The pain reduction was measured using the VAS score. Results: Twenty-seven patients with a mean age of 37.33 ± 9.84 years (24-55 years) were followed up for at least 12 months (12-31 months). The mean HHS at 12 months was 94.81 ± 8.18 (range: 68-100). Twenty-five patients were able to achieve radiological union within a mean time of 14.60 ± 4.69 weeks (range: 8-28). The overall complication rate was found to be 18.51% (5 out of 27 patients). Individual complications were non-union (2 patients; 7.4%), AVN (3 patients; 11.11%), and screw back out with femoral neck shortening (4 patients; 14.81%). Conclusion: Screw configuration using the BDSF technique provides a good union rate with minimum complications. The majority of patients resulted in a good (HHS >80) to excellent functional outcome. Based on the clinico-radiological outcome obtained, we conclude that this technique is effective in the fixation of FNF in adults. Level of study: Level II.

Free fatty acid-induced miR-181a-5p stimulates apoptosis by targeting XIAP and Bcl2 in hepatic cells.

AIMS: Non-alcoholic fatty liver disease is one of the major health concerns in the World. The dietary free fatty acids (FFAs) affect the metabolic status of the hepatocytes by modulating cellular pathways. In this study, we showed that free fatty acids stimulate apoptosis by upregulating miR-181a-5p expression, which in turn targets XIAP and Bcl2. METHODS: Huh7 cells were incubated with FFAs for 72 h and the expression of XIAP, Bcl2, bax, pAkt, Akt, PTEN and ß-actin were determined by Western blots, and miR-181a-5p expression was determined using real-time RT-PCR. The Huh7 cells were transfected with either miR-181a-5p pre-miRs or anti-miR-181a-5p and the regulation of apoptosis and proliferation was studied. Three groups of C57BL/6 mice (n = 6 per group) were fed with standard diet, CSAA or CDAA diet for 6, 18, 32 and 54 weeks. Total protein and RNA were isolated from the liver tissues and used for Western blots and real-time RT-PCR respectively. KEY FINDINGS: FFAs inhibited Akt phosphorylation, expression of XIAP and Bcl2, while upregulating the expression of PTEN, bax, and miR-181a-5p in Huh7 cells. Similar results were observed when the Huh7 cells were transfected with miR-181a-5p premiRs, while these changes were reversed in anti-miR-181a-5p-transfected, FFA-treated Huh7 cells. The CDAA-fed mice showed a significant inhibition of Akt phosphorylation, XIAP and Bcl2, whereas PTEN and bax expression were upregulated. The expression of miR-181a-5p was also significantly higher in CDAA-fed mice. SIGNIFICANCE: These findings showed that free fatty acids induced apoptosis via upregulating miR-181a-5p in hepatic cells.

Synovial Chondromatosis of Hip Joint in a Patient with Ankylosing Spondylitis: A Case Report.

Synovial chondromatosis in association with ankylosing spondylitis is extremely rare and has been reported only once before and this case report is presenting a similar case. The knee is the preferential site of involvement with involvement of the hip being reported sparsely. We herein report a case of a 52-year-old male who came with complaints of the lower back pain for 5 years and left hip pain for 1.5 years who was diagnosed with synovial chondromatosis of the hip joint with axial ankylosing spondylitis and was managed operatively. We here review briefly the clinical manifestations, pathogenesis, diagnosis, previously reported cases as well as treatment of synovial chondromatosis in patients with immune-mediated inflammatory arthritides. There should be a high index of suspicion to diagnose synovial chondromatosis in association with inflammatory arthritides. We also believe that surgical management is an effective method of treatment of an established synovial chondromatosis of the hip joint. Keywords: ankylosing spondylitis; case reports; hip joint; synovial chondromatosis.

Foraminal Stenosis at L5-S1 as an Overlooked Pathology of Bilateral Radiculopathy: A Case Series.

Introduction: The classical symptom of foraminal stenosis is unilateral radiculopathy. Bilateral radiculopathy caused purely by foraminal stenosis is rare. Here, we report five cases of bilateral L5 radiculopathy caused purely by L5-S1 foraminal stenosis and describe the clinical and radiological features of these patients in detail. Case Presentation: Among the five patients, two were men and three were women with an average age of 69 years. Four patients had undergone surgeries at L4-5 level, previously. All the patients showed an improvement in symptoms in the post-operative period. After a certain period, the patients complained of bilateral leg pain and numbness. An additional surgery was performed in two patients; however, there was no improvement in symptoms. One patient, who did not undergo surgery, was treated conservatively for 3 years. All the patients had been suffering from bilateral leg symptoms before their first visit to our hospital. The neurological findings in these patients were consistent with bilateral L5 radiculopathy. The average pre-operative Japanese Orthopedic Association (JOA) score was 13 out of 29 points. Bilateral foraminal stenosis at L5-S1 level was confirmed using a three-dimensional magnetic resonance imaging or computed tomography. Posterior lumbar interbody fusion was performed in one patient and bilateral lateral fenestration using Wiltse's approach was performed in four patients. The neurological symptoms recovered immediately after surgery. The average JOA score at 2-year follow-up was 25 points. Conclusions: Spine surgeons may overlook the pathology of foraminal stenosis, particularly in patients with bilateral radiculopathy. Familiarity with the clinical and radiological features of symptomatic lumbar foraminal stenosis is necessary to properly diagnose bilateral foraminal stenosis at L5-S1 level.

Should fluorodeoxyglucose positron emission tomography/computed tomography be the first-line imaging investigation for restaging the laryngeal carcinoma patients?

Posttreatment detection of residual/recurrence disease in the head and neck cancers is not an easy task. Treatment induces changes create difficulties in diagnosis on conventional imaging (computed tomography [CT], magnetic resonance imaging) as well as macroscopic inspection (direct laryngoscopy). Hence, we evaluate the diagnostic performance of contract-enhanced F-18 fluorodeoxyglucose positron emission tomography (FDG PET)/CT in restaging of laryngeal carcinoma Postchemotherapy-surgery and/or radiation therapy. We retrospectively analyzed patients of carcinoma larynx (n = 100) who has completed treatment and were referred for FDG PET/CT. Two reviewers performed image analysis to determine recurrence at primary site and/lymph nodes and distant metastases. Receiver operating characteristic (ROC) was used to determine the maximum standardized uptake value (SUVmax) cut off for disease detection. Histopathological examination and clinical or imaging follow-up were taken as gold standard for recurrence. One hundred laryngeal carcinoma patients with mean age of 57.2 years (range of 40-76) were included in the present study. Among the 100 patients, 96 were male and remaining 4 were female. The average interval between completion of treatment and FDG PET/CT scan was 8.5 months (minimum 6 months). Of the 100 patients, FDG PET/CT detected FDG avid lesions in 66 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of FDG PET/CT for residual/recurrence disease detection was 90.3%, 73.7%, 84.8%, 82.3%, and 84.0%, respectively (P < 0.05). In addition, in 10 patients, metachronous primaries were detected (lung-4, thyroid-2, tongue, colon, esophagus, and lymphoma-one each). On ROC curve analysis, SUVmax >6.1 had sensitivity and specificity of 80.6% and 94.7% respectively for detection of recurrent/metastatic disease. FDG PET/CT demonstrates high diagnostic accuracy for detection of residual/recurrent disease in treated laryngeal cancer patients and our findings suggest that this imaging modality should be the first-line diagnostic investigation in this cohort of patients.

TLR22-mediated activation of TNF-α-caspase-1/IL-1ß inflammatory axis leads to apoptosis of Aeromonas hydrophila-infected macrophages.

Toll-like receptors (TLRs) represent first line of host defence against microbes. Amongst different TLRs, TLR22 is exclusively expressed in non-mammalian vertebrates, including fish. The precise role of TLR22 in fish-immunity remains abstruse. Herein, we used headkidney macrophages (HKM) from Clarias gariepinus and deciphered its role in fish-immunity. Highest tlr22 expression was observed in the immunocompetent organ - headkidney; nonetheless expression in other tissues suggests its possible involvement in non-immune sites also. Aeromonas hydrophila infection up-regulates tlr22 expression in HKM. Our RNAi based study suggested TLR22 restricts intracellular survival of A. hydrophila. Inhibitor and RNAi studies further implicated TLR22 induces pro-inflammatory cytokines TNF-α and IL-1ß. We observed heightened caspase-1 activity and our results suggest the role of TLR22 in activating TNF-α/caspase-1/IL-1ß cascade leading to caspase-3 mediated apoptosis of A. hydrophila-infected HKM. We conclude, TLR22 plays critical role in immune-surveillance and triggers pro-inflammatory cytokines leading to caspase mediated HKM apoptosis and pathogen clearance.

Clinical and oncological outcomes of surgery in Anorectal melanoma in Asian population: A 15 year analysis at a tertiary cancer institute.

INTRODUCTION: Anorectal malignant melanoma (ARMM) is an aggressive malignancy with dismal prognosis and a 5-year survival rate less than 20% in most of the previous studies. The ideal surgical treatment has still remained controversial. This retrospective study aims at analysing the outcome in patients with ARMM treated with curative surgical resection. PATIENTS AND METHODS: This is a retrospective study of 38 patients of stage I anorectal malignant melanoma treated with curative surgical resection at our tertiary cancer institute. RESULTS: WLE (Wide Local Excision) was carried out in 12 patients and APR (abdominoperineal resection) was done in 26 patients. The median overall survival of the entire group in this study was 20 months. Although the median overall survival of WLE patients was higher than those with APR (37 months versus 16 months, respectively), this was not a statistically significant event (P=0.317). The 1-, 2-, 3-, 5-year survival rates were similar with both APR and WLE with no significant difference in the 5-year survival rate (P=0.816); overall 5-year survival rate of just 13%. There were 3 long-term survivors in this study group who survived for more than 10 years. CONCLUSION: Most patients ultimately succumb to the disease regardless of the management. Both APR and WLE have significant roles in the management depending on the subset of patients selected. Local treatment should be preferred wherever possible. Abdominoperineal resection should be offered in nodal disease or in a recurrent setting.

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin. METHODS: This open-label randomized trial was designed to compare pemetrexed-carboplatin with (weekly) paclitaxel-carboplatin in treatment-naïve advanced/metastatic non-squamous NSCLC without driver mutations. Patients received either pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks, or paclitaxel 80 mg/m2 on day 1, day 8, and day 15 with carboplatin AUC 5 every 4 weeks for 4 cycles. Patients in both arms were allowed to receive pemetrexed maintenance. RESULTS: A total of 180 patients were enrolled. The study was terminated early; however, at the time of analysis 75.8% of the required events had occurred. Finally, 164 patients were evaluable, 83 in the pemetrexed arm and 81 in the paclitaxel arm. After a median follow-up of 17 months, progression-free survival (PFS) rates at 6 months were not different in the two treatment arms (47.45 vs. 48.64%, p = 0.88). The median PFS values were 5.67 months (95% CI 3.73-7.3) and 5.03 months (95% CI 2.63-7.43) in each arm, respectively (HR 1.13, 95% CI 0.81-1.59, p = 0.44). The median overall survival was also not different: 14.83 months (95% CI 9.5-18.73) and 11.3 (95% CI 8.3-19.7; HR 1.19, 95% CI 0.8-1.78, p = 0.37). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were higher in the paclitaxel arm. CONCLUSION: Pemetrexed-carboplatin is not superior to (weekly) paclitaxel-carboplatin as the first-line regimen in advanced non-squamous NSCLC in terms of PFS.

Soft tissue aneurysmal bone cyst of left hemithorax with review of literature.

Soft tissue aneurysmal bone cysts (STABCs) are extremely rare extraosseous counterpart of aneurysmal bone cyst (ABC), with close resemblance to histo-morphologic characteristics of ABC. Here we would like to report a 13-year-old female patient, who presented with a large mass, occupying the entire left hemithorax. Patient underwent resection of the thoracic mass. On histopathological examination, it was found to be a soft tissue ABC. It is a very rare tumor and until date 28 cases have been reported in English literature, to the best of our knowledge. On review of the literature, we found this to be the first case of STABC reported in thoracic cavity. The objective of this case presentation is to provide information regarding clinical presentation, radiological and pathological features, and course of management for this rare disease. Soft tissue ABCs are a new class of tumors, so more extensive research is required to establish standard guidelines for their diagnosis and management, to yield better prognosis.

A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) differentially affect glutamate induced excitotoxic responses in chicken cerebellum granule neurons (CGNs) in vitro.

Primary cultures of cerebellar granule neurons (CGNs) derived from chicken embryos were used to explore the effects on developmental neurotoxicity by a complex defined mixture of persistent organic pollutants (POPs). Its chemical composition and concentrations were based on blood levels in the Norwegian/Scandinavian population. Perfluorooctane sulfonic acid (PFOS) alone, its most abundant compound was also evaluated. Different stages of CGNs maturation, between day in vitro (DIV) 1, 3, and 5 were exposed to the POP mixture, or PFOS alone. Their combination with glutamate, an excitatory endogenous neurotransmitter important in neurodevelopment, also known to cause excitotoxicity was evaluated. Outcomes with the mixture at 500x blood levels were compared to PFOS at its corresponding concentration of 20 µM. The POP mixture reduced tetrazolium salt (MTT) conversion at earlier stages of maturation, compared to PFOS alone. Glutamate-induced excitotoxicity was enhanced above the level of that induced by glutamate alone, especially in mature CGNs at DIV5. Glutathione (GSH) concentrations seemed to set the level of sensitivity for the toxic insults from exposures to the pollutants. The role of N-methyl-D-aspartate receptor (NMDA-R) mediated calcium influx in pollutant exposures was investigated using the non-competitive and competitive receptor antagonists MK-801 and CGP 39551. Observations indicate a calcium-independent, but still NMDA-R dependent mechanism in the absence of glutamate, and a calcium- and NMDA-R dependent one in the presence of glutamate. The outcomes for the POP mixture cannot be explained by PFOS alone, indicating that other chemicals in the mixture contribute its overall effect.

Advancement of nanoscience in development of conjugated drugs for enhanced disease prevention.

Nanoscience and nanotechnology is a recently emerging and rapid developing field of science and has also been explored in the fields of Biotechnology and Medicine. Nanoparticles are being used as tools for diagnostic purposes and as a medium for the delivery of therapeutic agents to the specific targeted sites under controlled conditions. The physicochemical properties of these nanoparticles give them the ability to treat various chronic human diseases by site specific drug delivery and to use in diagnosis, biosensing and bioimaging devices, and implants. According to the type of materials used nanoparticles can be classified as organic (micelles, liposomes, nanogels and dendrimers) and inorganic (including gold nanoparticles (GNPs), super-paramagnetic iron oxide nanomaterials (SPIONs), quantum dots (QDs), and paramagnetic lanthanide ions). Different types of nanoparticle are being used in conjugation with various types of biomoities (such as peptide, lipids, antibodies, nucleotides, plasmids, ligands and polysaccharides) to form nanoparticle-drug conjugates which has enhanced capacity of drug delivery at targeted sites and hence improved disease treatment and diagnosis. In this study, the summary of various types of nanoparticle-drug conjugates that are being used along with their mechanism and applications are included. In addition, the various nanoparticle-drug conjugates which are being used and which are under clinical studies along with their future opportunities and challenges are also discussed in this review.

A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) enhance nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells.

Disruption of neurite outgrowth is a marker for neurotoxicity. Persistent organic pollutants (POPs) are potential developmental neurotoxicants. We investigated their effect on neurite outgrowth in PC12 rat pheochromocytoma cells, in absence or presence of nerve growth factor (NGF), an inducer of neuronal differentiation. Cells were exposed for 72 h to a defined mixture of POPs with chemical composition and concentrations based on blood levels in the Scandinavian population. We also evaluated perfluorooctane sulfonic acid (PFOS) alone, the most abundant compound in the POP mixture. Only higher concentrations of POP mixture reduced tetrazolium salt (MTT) conversion. High-content analysis showed a decrease in cell number, but no changes for nuclear and mitochondrial cellular health parameters. Robust glutathione levels were observed in NGF-differentiated cells. Live imaging, using the IncuCyte ZOOM platform indicated ongoing cell proliferation over time, but slower in presence of NGF. The pollutants did not inhibit neuritogenesis, but rather increased NGF-induced neurite length. PFOS induced neurite outgrowth to about 50 % of the level seen with the POP mixture. Neither the POP mixture nor PFOS affected neurite length in the absence of NGF. Our observations indicate that realistic complex mixtures of environmental pollutants can affect neuronal connectivity via NGF-induced neurite outgrowth.