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Modified radical mastectomy (MRM) is still the most commonly performed operation for breast cancer, despite the trends toward breast-conserving treatment. Since 1970s, electrosurgery (also known as electrocautery, diathermy) has been a widespread surgical tool to raise flaps and excise the breast specimen in order to perform a bloodless mastectomy. Use of diathermy has been well blamed for wound complications. To prevent undue delay in the adjuvant treatment, it is important to minimize the surgical complications. This quasi experimental study was conducted in the Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh to evaluate the effects of electrosurgery and sharp dissection on early postoperative wound complications in MRM. 46 patients were included in the study (23 in each group). Data analysis done in SPSS version 23.0 and 'p' value <0.05 considered significant at 95% confidence interval. In Electrosurgery Dissection (ED) group mean duration of drainage was 7.8±1.2 days and in Sharp Dissection (SD) group 6.4±1.0 days (p value 0.000). Mean total drainage in ED group found 1082±287ml and in SD group 693±194ml (p value 0.000). Seroma formation found 7(30.4%) in ED group and 3(13.0%) in SD group (p value 0.004). Wound dehiscence found 5(21.7%) in ED group and 2(8.7%) in SD group (p value 0.013). Flap necrosis rate was 4(17.4%) and 1(4.4%) in ED and SD group respectively (p=0.003). Demographic and clinical variables were similar or differences were not statistically significant in two groups. No difference found in operating time and wound infection rate in two groups. The result of the study showed that, electrocautery dissection caused early postoperative wound complications more than the sharp dissection.

To evaluate the diagnostic utility of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) of pancreatic lesions, EUS-FNA was carried out on a total of 28 cases at the Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from June 2015 to August 2016. Clinical impression was compared with the final cytological diagnosis and the percentage of non diagnostic smears was calculated. The lesions were categorized according to cytological report. Out of 28 cases, 3(10.71%) cases were normal, 6 cases (21.43%) were reported as inconclusive while a definite diagnosis was given in 19 cases (67.85%). The mean patient age was 47.82 years. There were 16(57.1%) males and 12(42.9%) females. The most common site biopsied was pancreatic head in 21cases (75%) followed by tail in 5 cases (17.9%) & body in 2(7.1%) cases. The average number of passes made was two. Endoscopic Ultrasound Guided Fine-Needle Aspiration in the diagnosis of pancreatic lesion is a useful procedure.

The Solitaire (Medtronic Inc, Mansfield, Massachusetts, USA) is a stentriever device for endovascular treatment of acute ischemic stroke. Temporary endovascular bypass and mechanical thrombectomy are well-described applications of this device. However, few reports of permanent stent placement have been published. We present a series of five cases in which the Solitaire stent was implanted to restore distal flow after failure of conventional mechanical thrombectomy. All patients presented with large vessel occlusions with thrombi that were resistant to retrieval or suction-aspiration. Immediately after implantation the patients were given a loading dose of abciximab and then transitioned to dual antiplatelet therapy within 24 hours. Our series suggests that permanent deployment of the Solitaire may be considered as a bailout technique in the treatment of cerebral large vessel occlusion. Long-term antiplatelet therapy is required after deployment., Competing Interests: Competing interests: MEK: consultant, Medtronic; LP: consultant, Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The analysis of heterogeneous subpopulations of circulating tumor cells (CTCs) is critical to enhance our understanding of cancer metastasis and enable noninvasive cancer diagnosis and monitoring. The phenotypic variability and plasticity of these cells-properties closely linked to their clinical behavior-demand techniques that isolate viable, discrete fractions of tumor cells for functional assays of their behavior and detailed analysis of biochemical properties. Here, we introduce the Prism Chip, a high-resolution immunomagnetic profiling and separation chip which harnesses a cobalt-based alloy to separate a flowing stream of nanoparticle-bound tumor cells with differential magnetic loading into 10 discrete streams. Using this approach, we achieve exceptional purity (5.7 log white blood cell depletion) of isolated cells. We test the differential profiling function of the integrated device using prostate cancer blood samples from a mouse xenograft model. Using integrated graphene Hall sensors, we demonstrate concurrent automated profiling of single cells and CTC clusters that belong to distinct subpopulations based on protein surface expression.

Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA-damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133 + GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133 - non-GSC in vitro ; immunofluorescence studies confirmed these observations in a panel of orthotopic xenografts and human GBM specimens. Exposure of non-GSC to low-level exogenous RS generated radiation resistance in vitro , confirming RS as a novel determinant of radiation resistance in tumor cells. GSC exhibited DNA double-strand breaks, which colocalized with "replication factories" and RNA: DNA hybrids. GSC also demonstrated increased expression of long neural genes (>1 Mbp) containing common fragile sites, supporting the hypothesis that replication/transcription collisions are the likely cause of RS in GSC. Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance in vitro These data identify RS as a cancer stem cell-specific target with significant clinical potential. Significance: These findings shed new light on cancer stem cell biology and reveal novel therapeutics with the potential to improve clinical outcomes by overcoming inherent radioresistance in GBM. Cancer Res; 78(17); 5060-71. ©2018 AACR ., (©2018 American Association for Cancer Research.)

The exploitation of semiconductor nanocrystal (NC) films in novel electronic and optoelectronic applications requires a better understanding of charge transport in these systems. Here, we develop a model of charge transport in NC films, based on a generalization of the concept of transport energy level ET to nanocrystal assemblies, which considers both intra- and inter-NC charge transfer processes. We conclude that the role played by each of these processes can be probed from temperature-dependent measurements of charge carrier density n and mobility μ in the same films. The model also enables the determination of the position of the Fermi energy level EF with respect to ET, an important parameter of charge transport in semiconductor materials, from the temperature dependence of n. Moreover, we provide support to an essentially temperature-independent intra-NC charge carrier mobility, considered in the transport level concept, and consequently the frequently observed temperature dependence of the overall mobility μ in NC films results from a temperature variation of the inter-NC charge transport processes. Importantly, we also conclude that the temperature dependence of conductivity in NC films should result in general from a combination of temperature variations of both n and μ. By applying the model to solution-processed Si NC films, we conclude that transport within each NC is similar to that in amorphous Si (a-Si), with charges hopping along band tail states located below the conduction band edge. For Si NCs, we obtain values of ET - EF of ∼0.25 eV. The overall mobility μ in Si NC films is significantly further reduced with respect to that typically found in a-Si due to the additional transport constraints imposed by inter-NC transfer processes inherent to a nanoparticulate film. Our model accounting for inter- and intra-NC charge transport processes provides a simple and more general description of charge transport that can be broadly applied to films of semiconductor NCs.

Background: Splanchnic venous thrombosis (SVT) is a common vascular complication of acute pancreatitis (AP). We conducted this study to prospectively investigate the frequency, risk factors, and extent of SVT in patients with AP and to evaluate the role of thrombophilia in its causation., Methods: Patients with AP presenting between January 2015 and June 2016 were prospectively evaluated with contrast-enhanced computed tomography (CT) for the presence of SVT. These patients underwent a detailed analysis of coagulation parameters., Results: We evaluated 96 patients with AP (73 male, mean age 31.85±13.34 years), of whom 26 (27.1%) had SVT. Splenic vein, portal vein, and superior mesenteric vein involvement were seen in 22 (84.6%), 11 (42.3%), and 4 (15.3%) patients, respectively. Necrotizing pancreatitis, CT severity index (CTSI) >6 and modified CTSI >6 were significantly more frequent in patients with SVT than in those without (96.2% vs. 78.6%, 76.9% vs. 47.1%, and 92.3% vs. 67.1%, respectively). Proteins C and S, and antithrombin III deficiency were found in 23.8%, 33.3% and 31.0% of patients, respectively. Anti-β2-glycoprotein I and lupus anticoagulant were positive in 4.8% and 11.9% of patients, respectively. Factor V Leiden mutation analysis was positive in 6.1% of patients. Coagulation abnormality did not differ significantly between the patients with and without SVT., Conclusions: SVT is more common in patients with necrotizing pancreatitis, suggesting that local inflammation plays a major role in its causation. Thrombophilia is seen in one third of patients with AP but does not seem to increase the risk of SVT., Competing Interests: Conflict of Interest: None

Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients' clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared with both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared with more superior segments). Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.

Cell-to-cell variation in gene expression creates a need for techniques that can characterize expression at the level of individual cells. This is particularly true for rare circulating tumour cells, in which subtyping and drug resistance are of intense interest. Here we describe a method for cell analysis-single-cell mRNA cytometry-that enables the isolation of rare cells from whole blood as a function of target mRNA sequences. This approach uses two classes of magnetic particles that are labelled to selectively hybridize with different regions of the target mRNA. Hybridization leads to the formation of large magnetic clusters that remain localized within the cells of interest, thereby enabling the cells to be magnetically separated. Targeting specific intracellular mRNAs enablescirculating tumour cells to be distinguished from normal haematopoietic cells. No polymerase chain reaction amplification is required to determine RNA expression levels and genotype at the single-cell level, and minimal cell manipulation is required. To demonstrate this approach we use single-cell mRNA cytometry to detect clinically important sequences in prostate cancer specimens.

Background: Neurosurgical residents face a unique combination of challenges, including long duty hours, technically challenging cases, and uncertain employment prospects. We sought to assess the demographics, interests, career goals, self-rated happiness, and overall well-being of Canadian neurosurgery residents., Methods: A cross-sectional survey was developed and sent through the Canadian Neurosurgery Research Collaborative to every resident enrolled in a Canadian neurosurgery program as of April 1, 2016., Results: We analyzed 76 completed surveys of 146 eligible residents (52% response rate). The median age was 29 years, with 76% of respondents being males. The most popular subspecialties of interest for fellowship were spine, oncology, and open vascular neurosurgery. The most frequent self-reported number of worked hours per week was the 80- to 89-hour range. The majority of respondents reported a high level of happiness as well as stress. Sense of accomplishment and fatigue were reported as average to high and overall quality of life was low for 19%, average for 49%, and high for 32%. Satisfaction with work-life balance was average for 44% of respondents and was the only tested domain in which significant dissatisfaction was identified (18%). Overall, respondents were highly satisfied with their choice of specialty, choice of program, surgical exposure, and work environment; however, intimidation was reported in 36% of respondents and depression by 17%., Conclusions: Despite a challenging residency and high workload, the majority of Canadian neurosurgery residents are happy and satisfied with their choice of specialty and program. However, work-life balance, employability, resident intimidation, and depression were identified as areas of active concern.

The peritoneum is involved in many diseases such as primary malignancy (mesothelioma), infectious disease (tuberculosis), and disseminated malignancy (peritoneal carcinomatosis). The peritoneal disease may manifest as ascites and/or peritoneal masses or nodules. Endoscopic ultrasound (EUS), due to its ability to provide high-resolution images, has revolutionized the imaging and diagnosis of pancreaticobiliary diseases among other gastrointestinal conditions. EUS can not only help in imaging of various lesions close to the gastrointestinal lumen but also aspirate/biopsy them. We conducted a systematic search to identify published literature on the value of EUS in detection and diagnosis of peritoneal disorders. This review aims to summarize the available literature on the use of EUS-guided paracentesis and fine-needle aspiration from peritoneal nodules.

Background: Although spinal cord stimulation (SCS) therapy has been shown to be efficacious in various pain conditions, the ability for SCS therapy to maintain long-term efficacy has been questioned., Objective: The purpose of this study was to investigate whether a loss of efficacy (LOE) phenomenon exists with SCS therapy and to investigate if this phenomenon is more apparent in any specific patient population., Study Design: A retrospective, observation chart review was conducted to evaluate the patient response to SCS therapy over time., Setting: Massachusetts General Hospital, Boston, Massachusetts., Methods: Patients who received a SCS at the Massachusetts General Hospital, between January 1, 2002 and December 31, 2012, were invited to participate. A total of 62 patients were included in this study. Various models were created to analyze pain score changes over time using 2-tailed statistical analysis. Additionally, one-way ANOVA and Pearson's chi-square tests were used to determine if certain patient characteristics were associated with LOE., Results: Compared to the visual analog scale (VAS) score at one month after device implantation, pain scores increased 1.95 points after 2 years (95% CI: 1.06 to 2.84, P = < 0.001). There were no significant differences in baseline characteristics between the groups of patients who did and did not lose efficacy of their therapy. However, those who experienced LOE had a baseline SCS therapy VAS score 3.09 points lower than those who did not (95% CI: 1.69 to 4.48, P = < 0.001)., Limitations: This study had several limitations including the retrospective nature of its design, confounders to VAS scores, small sample size, missing data points, and the evaluation of only conventional, low-frequency SCS therapy., Conclusions: Patients who received a SCS had a significant increase in VAS scores over time. Our data did not show any baseline patient characteristic that helped predict LOE. However, patients who have significant baseline response to therapy may be more likely to experience LOE., Key Words: Spinal cord stimulation, chronic pain, retrospective study, low frequency electrical stimulation, efficacy, chronic pain therapy.

Background: Acute necrotizing pancreatitis (ANP) is complicated with segmental portal hypertension (PHT) and formation of venous collaterals. Presence of collaterals in vicinity of endoscopic transmural tract can lead to potentially catastrophic situation. Here, we report safety and outcome of EUS-guided transmural drainage of walled-off pancreatic necrosis (WOPN) in patients with PHT and intra-abdominal collaterals., Methods: Retrospective analysis of collected database of patients (n=18; age 40.94±8.43 years; 17 males) who underwent EUS-guided transmural drainage of WOPN and had PHT with collaterals., Results: Etiology of ANP: alcohol in 14 and gallstones in 3 patients. Mean size of collection was 10.7±3.5 cm, and all 18 patients had splenic vein thrombosis with 1 patient also having portal vein thrombosis. Drainage was not feasible in 1 patient as no window free of collaterals could be found. One patient with gastric variceal bleeding underwent drainage after successful obliteration of varix with glue. Multiple plastic stents were placed in 15 patients and fully covered self-expanding metallic stent (FCSEMS) in 1 patient and 1 patient required direct endoscopic necrosectomy (DEN). Mean procedures required were 3 ± 0.79 and time to resolution was 4.4 ± 1.3 weeks. One patient had post-drainage bleeding that was successfully managed with intravenous terlipressin and intermittent irrigation via nasocystic catheter. Successfully treated patients have been asymptomatic over follow up period of 15.65±12.2 weeks., Conclusion: EUS-guided drainage of WOPN seems to be safe and effective in patients with portal hypertension and intra-abdominal collaterals.

Background: Euphorbia hirta linn., is a species of Euphorbiaceae family. They are known as asthma plant, barokhervi. The plant E. hirta is famous for its medicinal importance among the tribal population. It is a common practice to use the whole to heal wounds. Several pharmacological properties including antiseptic, anti-inflammatory, antidibetic, antispasmodic, antibacterial, antiviral, antifungal, anticonvulsant, nootropic, antifertility and aphrodisiac properties have already been reported for this plant. The aim of present work was to evaluate the wound healing property in diabetic animals by oral and topical administration of ethanolic extract of E. hirta whole plant., Methods: The ethanolic extract of E. hirta was subjected to determine the total phenolic content and total flavonoid content using galic acid and quercetin, respectively as standard. A single injection of alloxan monohydrate (120 mg/kg, i.p.) prepared in normal saline was administered to produce diabetes in rats, after overnight fasting. For analyzing the rate of contraction of wound, excision wounds sized 4.90cm 2 and of 2 mm depth were used. Oral (100, 200 and 400 mg/kg/day; p.o.) and topical treatment with the extract (5% and 10% ointment 50 mg/kg/day) and standard (5% povidone iodine ointment 50 mg/kg/day) was started on the day of induction of wound and continued up to 16 days. The means of wound area measurement between groups at different time intervals were compared using ANOVA and Dunnet's test. The diabetic wound healing mechanism was studied by measuring the plasma level of glucose, malondialdehyde (MDA) and nitric oxide (NO) in both control and treated groups. For the confirmation of activity, histopathology of the wounds tissues from excision wound model was performed., Results: Phytochemical investigations showed the presence of various phytoconstituents (carbohydrates, saponins, alkaloids, glycosides, steroids, flavonoids, tannins). In the ethanolic extract of E. hirta the total phenol content was 285 ± 3.22 mg/g whereas the total flavonoid content was 118.46 ± 1.85 mg/g. In the present study, E. hirta caused significant wound closer both orally (35.92%, 44.69% and 61.42% at the doses of 100, 200 and 400, respectively) and topically (32.86% and 36.32% at the doses of 5% and 10%) treated groups as compared to diabetic control. However, the orally treated groups showed more significant effect than the topically treated groups. Moreover, oral administration of E. hirta ethanolic extract significantly reduced the blood glucose levels in diabetic wound rats (p < 0.01) on day 8 and day 16 as compared to the diabetic wound control (p < 0.01). On the other hand, topical application of E. hirta did not influence the blood glucose levels in diabetic rats (p > 0.05). It also demonstrated a significant decrease in the plasma levels of lipid malondialdehyde and nitric oxide. The results of biochemical parameters were further supported by the histopathological changes of different organs (liver, pancrease, kidney, heart and skin from wound area) which were evidenced through a decrease in inflammatory cell infiltration., Conclusion: The present study demonstrates that E. hirta whole plant extract promotes healing of wounds more significantly as compared to diabetic control rats, where healing is otherwise delayed.

Background Currently, the literature lacks reliable data regarding operative case volumes at Canadian neurosurgery residency programs. Our objective was to provide a snapshot of the operative landscape in Canadian neurosurgical training using the trainee-led Canadian Neurosurgery Research Collaborative., Methods: Anonymized administrative operative data were gathered from each neurosurgery residency program from January 1, 2014, to December 31, 2014. Procedures were broadly classified into cranial, spine, peripheral nerve, and miscellaneous procedures. A number of prespecified subspecialty procedures were recorded. We defined the resident case index as the ratio of the total number of operations to the total number of neurosurgery residents in that program. Resident number included both Canadian medical and international medical graduates, and included residents on the neurosurgery service, off-service, or on leave for research or other personal reasons., Results: Overall, there was an average of 1845 operative cases per neurosurgery residency program. The mean numbers of cranial, spine, peripheral nerve, and miscellaneous procedures were 725, 466, 48, and 193, respectively. The nationwide mean resident case indices for cranial, spine, peripheral nerve, and total procedures were 90, 58, 5, and 196, respectively. There was some variation in the resident case indices for specific subspecialty procedures, with some training programs not performing carotid endarterectomy or endoscopic transsphenoidal procedures., Conclusions: This study presents the breadth of neurosurgical training within Canadian neurosurgery residency programs. These results may help inform the implementation of neurosurgery training as the Royal College of Physicians and Surgeons residency training transitions to a competence-by-design curriculum.

Isolating subpopulations of heterogeneous cancer cells is an important capability for the meaningful characterization of circulating tumor cells at different stages of tumor progression and during the epithelial-to-mesenchymal transition. Here, we present a microfluidic device that can separate phenotypically distinct subpopulations of cancer cells. Magnetic nanoparticles coated with antibodies against the epithelial cell adhesion molecule (EpCAM) are used to separate breast cancer cells in the microfluidic platform. Cells are sorted into different zones on the basis of the levels of EpCAM expression, which enables the detection of cells that are losing epithelial character and becoming more mesenchymal. The phenotypic properties of the isolated cells with low and high EpCAM are then assessed using matrix-coated surfaces for collagen uptake analysis, and an NAD(P)H assay that assesses metabolic activity. We show that low-EpCAM expressing cells have higher collagen uptake and higher folate-induced NAD(P)H responses compared to those of high-EpCAM expressing cells. In addition, we tested SKBR3 cancer cells undergoing chemically induced hypoxia. The induced cells have reduced expression of EpCAM, and we find that these cells have higher collagen uptake and NAD(P)H metabolism relative to noninduced cells. This work demonstrates that nanoparticle-mediated binning facilitates the isolation of functionally distinct cell subpopulations and allows surface marker expression to be associated with invasiveness, including collagen uptake and metabolic activity.

Background: The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity., Methods: The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa., Results: P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract's doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema., Conclusions: The investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.

Introduction: Neurological manifestations although common in Systemic Lupus Erythematosus (SLE), are often not recognized due to their diversed and varied presentation. Therefore, the study was planned to highlight the pattern of neurological involvement in SLE to help in early recognition., Aim: To study the pattern of neurological involvement in SLE and its correlation with disease activity and different investigation., Materials and Methods: This hospital based prospective observational study was carried out from August 2009 to July 2010. Diagnosed cases of SLE [based upon American Rheumatism Association (ARA) criteria] who presented with neurological manifestations at the time of diagnosis or develop during the course of the disease were included in the study. They were assessed clinically and investigated with neuroimaging and neurophysiological tests as applicable., Results: In total, 52 consecutive patients with SLE were evaluated, 92% were female. The most common age group was 21 to 25 years. Nervous system involvement was found in 19 (36.54%) patients. Cognitive impairment was the most frequent manifestation, present in 11 (57.89%) patients followed by seizure disorder in eight patients (42.1%). Peripheral neuropathy was diagnosed in eight (42.1%), acute confusional state in six (31.57%) and headache and depression was diagnosed in five (26.31%) patients each. Less common manifestations were psychosis, movement disorder and aseptic meningitis. Percentage of neurological manifestations directly correlated with disease activity. A significant difference was found in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score between the patients with Neuro Psychiatric Systemic Lupus Erythematosus (NPSLE) and those without NPSLE (32.42±16.34 Vs 17.3±10.6)., Conclusion: Neurological involvement in SLE is seen relatively early in the course of the disease with cognitive impairment being the most common manifestation and correlate with disease activity.

Objective: To assess the evidence base for high-frequency spinal cord stimulation (HFSCS). HFSCS has the potential to provide paresthesia-free pain relief for patients with chronic pain, in contrast to conventional spinal cord stimulation, which produces distracting and potentially unpleasant paresthesias., Design: A systematic review following standard methodological guidelines (Prospero #CRD42015029215)., Methods: We searched PubMed to March 14, 2016 without language restriction and hand-checked reference lists. Two authors independently performed study selection, bias evaluations, and data extraction. The pre-clinical review selected studies focusing on the mechanism and non-human experience with HFSCS. Clinically, any prospective study of adults using HFSCS (≥ 1000 Hz) was included., Results: Pre-clinical studies have characterized many aspects underlying the mechanism of HFSCS. For the clinical systematic review, eight trials (236 participants randomized or 160 followed prospectively) met inclusion criteria. All trials of HFSCS focused on patients with chronic low back pain with one exception, which included patients with chronic migraine. All but one trial documented funding by industry. Performance bias due to unmasked participants, physicians, and outcome assessors limited the quality of all but one study., Conclusions: Significant growth in the preclinical and clinical evidence base for HFSCS suggests that HFSCS may differ from conventional SCS in mechanism of action and efficacy of treatment, respectively. Addressing current knowledge gaps in clinical evidence will require standardization in trial reporting and leveraging the paresthesia-free characteristic of HFSCS to enable masking in high-quality randomized controlled trials., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Glioblastoma multiforme lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in glioblastoma multiforme, glioma cells exhibit intrinsic resistance toward many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here, we show that overexpression of the protein phosphatase 2A (PP2A) inhibitor protein PME-1 drives resistance of glioma cells to various multikinase inhibitors. The PME-1-elicited resistance was dependent on specific PP2A complexes and was mediated by a decrease in cytoplasmic HDAC4 activity. Importantly, both PME-1 and HDAC4 associated with human glioma progression, supporting clinical relevance of the identified mechanism. Synthetic lethality induced by both PME-1 and HDAC4 inhibition was dependent on the coexpression of proapoptotic protein BAD. Thus, PME-1-mediated PP2A inhibition is a novel mechanistic explanation for multikinase inhibitor resistance in glioma cells. Clinically, these results may inform patient stratification strategies for future clinical trials with selected kinase inhibitors in glioblastoma multiforme. Cancer Res; 76(23); 7001-11. ©2016 AACR., (©2016 American Association for Cancer Research.)

Morphological and molecular delimitation of Spirostomum species is currently under debate. We addressed species boundaries within the genus Spirostomum, using the ITS1-5.8S-ITS2 region and the secondary structure of the ITS2 molecule, and 18S and 28S (D1D2) sequences additionally. The Spirostomum ITS region is among the shortest within the ciliates hitherto studied. The Spirostomum ITS2 molecule matches the "ring model", but exhibits only two helices radiating from a common loop. According to comparative analyses, they very likely correspond to helices II and III of other eukaryotes. Our phylogenetic analyses of the ITS region revealed a complex genealogical structure within the genus Spirostomum. However, boundaries among Spirostomum species could not be unambiguously determined either by phylogenetic trees, networks or sequence divergence cutoffs, because ITS2 sequences transcended species boundaries of the following morphospecies: S. ambiguum, S. minus, S. subtilis and S. teres. According to molecular diversity analysis, this is very likely caused by polymorphism in S. minus and S. teres, and by the lack of variability in S. ambiguum and S. subtilis. No compensatory base changes (CBCs) were detected in helices of the ITS2 molecule between different Spirostomum species, documenting that CBC analysis per se is not able to effectively discriminate Spirostomum species., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Two colepid ciliates, Levicoleps taehwae nov. spec. and L. biwae jejuensis nov. subspec., were collected from the brackish water of the Taehwa River and a small freshwater pond in Jeju Island, South Korea, respectively. Their living morphology, infraciliature, and small subunit (SSU) rRNA gene sequences were determined using standard methods. Barrel-shaped L. taehwae nov. spec. is a small ciliate with an average size of 45 × 25 μm in vivo, about 15 ciliary rows each composed of 12 monokinetids and two perioral dikinetids, and two 20 μm-long caudal cilia. The sequence length and GC content of the SSU rRNA gene are 1,669 bp, 44.5%. This novel species is similar in body size to Coleps hirtus, and has six armor tiers and hirtus-type tier plates, and the same number of ciliary rows as C. hirtus; however, it can be distinguished from the latter by the absence of armor spines and its sequence similarity of SSU rRNA gene is about 92.8% which indicates that it is a distinct form. Levicoleps biwae jejuensis nov. subspec., is a medium colepid ciliate which has a barrel-shaped body, about 22 somatic kineties and 16 transverse ciliary rows, three mini adoral organelles, and four 15 μm-long caudal cilia. The sequence length and GC content of the SSU rRNA gene are 1,666 bp and 44.4%., (© 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.)

Cancer cells, and in particular those found circulating in blood, can have widely varying phenotypes and molecular profiles despite a common origin. New methods are needed that can deconvolute the heterogeneity of cancer cells and sort small numbers of cells to aid in the characterization of cancer cell subpopulations. Here, we describe a new molecular approach to capturing cancer cells that isolates subpopulations using two-dimensional sorting. Using aptamer-mediated capture and antisense-triggered release, the new strategy sorts cells according to levels of two different markers and thereby separates them into their corresponding subpopulations. Using a phenotypic assay, we demonstrate that the subpopulations isolated have markedly different properties. This system provides an important new tool for identifying circulating tumor cell subtypes.

L-Glutamine (Gln) functions physiologically to balance the carbon and nitrogen requirements of tissues. It has been proposed that in cancer cells undergoing aerobic glycolysis, accelerated anabolism is sustained by Gln-derived carbons, which replenish the tricarboxylic acid (TCA) cycle (anaplerosis). However, it is shown here that in glioblastoma (GBM) cells, almost half of the Gln-derived glutamate (Glu) is secreted and does not enter the TCA cycle, and that inhibiting glutaminolysis does not affect cell proliferation. Moreover, Gln-starved cells are not rescued by TCA cycle replenishment. Instead, the conversion of Glu to Gln by glutamine synthetase (GS; cataplerosis) confers Gln prototrophy, and fuels de novo purine biosynthesis. In both orthotopic GBM models and in patients, (13)C-glucose tracing showed that GS produces Gln from TCA-cycle-derived carbons. Finally, the Gln required for the growth of GBM tumours is contributed only marginally by the circulation, and is mainly either autonomously synthesized by GS-positive glioma cells, or supplied by astrocytes.

Glioblastoma is the most common form of primary brain tumor in adults and is essentially incurable. Despite aggressive treatment regimens centered on radiotherapy, tumor recurrence is inevitable and is thought to be driven by glioblastoma stem-like cells (GSC) that are highly radioresistant. DNA damage response pathways are key determinants of radiosensitivity but the extent to which these overlapping and parallel signaling components contribute to GSC radioresistance is unclear. Using a panel of primary patient-derived glioblastoma cell lines, we confirmed by clonogenic survival assays that GSCs were significantly more radioresistant than paired tumor bulk populations. DNA damage response targets ATM, ATR, CHK1, and PARP1 were upregulated in GSCs, and CHK1 was preferentially activated following irradiation. Consequently, GSCs exhibit rapid G2-M cell-cycle checkpoint activation and enhanced DNA repair. Inhibition of CHK1 or ATR successfully abrogated G2-M checkpoint function, leading to increased mitotic catastrophe and a modest increase in radiation sensitivity. Inhibition of ATM had dual effects on cell-cycle checkpoint regulation and DNA repair that were associated with greater radiosensitizing effects on GSCs than inhibition of CHK1, ATR, or PARP alone. Combined inhibition of PARP and ATR resulted in a profound radiosensitization of GSCs, which was of greater magnitude than in bulk populations and also exceeded the effect of ATM inhibition. These data demonstrate that multiple, parallel DNA damage signaling pathways contribute to GSC radioresistance and that combined inhibition of cell-cycle checkpoint and DNA repair targets provides the most effective means to overcome radioresistance of GSC., (©2015 American Association for Cancer Research.)

Three peritrichous ciliates, Zoothamnium arcuatum n. sp., Z. grossi n. sp., and Z. parahentscheli Sun et al., 2009, were collected from an estuary of the Taehwagang River, Korea. All these species were investigated based on live observations and silver staining, and their small subunit (SSU) rRNA gene was also sequenced. Zoothamnium arcuatum can be identified by a goblet-shaped colony, double-layered peristomial lip, and abstomally shortened row 3 of infundibular polykinety 3 (P3). Zoothamnium grossi is morphologically characterized by an alternately branched stalk with the lowest secondary stalk diverging from the main part of colony, asymmetrically bell-shaped zooids, and three short, parallel ciliary rows in P3. Phylogenetic analysis revealed that the three Zoothamnium species described in this paper clustered with other members of the family Zoothamniidae, as expected., (© 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.)

Objective: Spinal cord stimulation (SCS) has been in clinical use for nearly four decades. In earliest observations, researchers found a significant increase in pain threshold during SCS therapy without changes associated with touch, position, and vibration sensation. Subsequent studies yielded diverse results regarding how SCS impacts pain and other sensory thresholds. This pilot study uses quantitative sensory testing (QST) to objectively quantify the impact of SCS on warm sensation, heat pain threshold, and heat pain tolerance., Materials and Methods: Nineteen subjects with an indwelling SCS device for chronic pain were subjected to QST with heat stimuli. QST was performed on an area of pain covered with SCS-induced paresthesia and an area without pain and without paresthesia, while the SCS was turned off and on. The temperature at which the patient detected warm sensation, heat pain, and maximal tolerable heat pain was used to define the thresholds., Results: We found that all three parameters, the detection of warm sensation, heat pain threshold, and heat pain tolerance, were increased during the period when SCS was on compared with when it was off. This increase was observed in both painful and non-painful sites., Conclusion: The observed pain relief during SCS therapy seems to be related to its impact on increased sensory threshold as detected in this study. The increased sensory threshold on areas without pain and without the presence of SCS coverage may indicate a central (spinal and/or supra-spinal) influence from SCS., (© 2015 International Neuromodulation Society.)

Background: Neuropathic pain is a condition resulting from injury to the peripheral and/or central nervous system. Despite extensive research over the last several decades, neuropathic pain remains difficult to manage., Methods: The authors conducted a randomized, placebo-controlled, double-blinded, and crossover clinical trial to examine the effect of 1.5% topical diclofenac (TD) on neuropathic pain. The authors hypothesized that 1.5% TD would reduce the visual pain score and improve both quantitative sensory testing and functional status in subjects with neuropathic pain. The authors recruited subjects with postherpetic neuralgia and complex regional pain syndrome. The primary outcome was subject's visual pain score., Results: Twenty-eight subjects completed the study (12 male and 16 female) with the mean age of 48.8 yr. After 2 weeks of topical application, subjects in 1.5% TD group showed lower overall visual pain score compared with placebo group (4.9 [1.9] vs. 5.6 [2.1], difference: 0.8; 95% CI, 0.1 to 1.3; P = 0.04) as well as decreased burning pain (2.9 [2.6] vs. 4.3 [2.8], difference, 1.4; 95% CI, 0.2 to 2.6; P = 0.01). There were no statistical differences in constant pain, shooting pain, or hypersensitivity over the painful area between the groups. This self-reported improvement of pain was corroborated by the decreased pain summation detected by quantitative sensory testing. There were no statistically significant changes in functional status in these subjects. There were no complications in both groups., Conclusion: The findings indicate that 1.5% TD may serve as an effective treatment option for patients with neuropathic pain from postherpetic neuralgia and complex regional pain syndrome.

Breast tuberculosis is a rare form of tuberculosis. Moreover the disease is often overlooked and misdiagnosed as carcinoma or pyogenic abscess. Reports on breast tuberculosis have been few; reported incidence of breast tuberculosis amongst the total number of mammary conditions varies between 0.1 and 4 percent. Bilateral involvement is still more uncommon (3%). Here we report 3 cases of adult female ranging from 27 to 35 years who presented with 1 to 4 months history of firm lumps in both breasts and no axillary lymphadenopathy. Fine needle aspiration cytology (FNAC) of breast lump in all 3 cases were done but in 1 case showed evidence of tubercular mastitis and other 2 cases findings were inconclusive. Subsequent Excisional Biopsy of those 2 cases showed features of tuberculosis. All 3 were prescribed with four drug anti-tubercular treatments continued for 12 months in 2 cases and 9 months in other case depending upon their response. The lumps disappeared and ulcer healed after anti-tubercular treatment.

Hsp90 is a major protein involved in the stabilization of various proteins in cancer cells. The present investigation focused on the molecular docking simulation studies of flavanols as inhibitors of Hsp90 at the high affinity adenosine triphosphate (ATP) binding site and analyzed absorption, distribution, metabolism, excretion and toxicity (ADME-toxicity). The molecular docking analysis revealed that the flavanols showed competitive inhibition with ATP molecule at the active site and enhanced pharmacological parameters., (© 2016 the Journal of Biomedical Research. All rights reserved.)

During apoptosis, the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases. Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell, leading to rapid caspase activation and apoptosis. Using a new imaging approach, we demonstrate that MOMP is not an all-or-nothing event. Rather, we find that a minority of mitochondria can undergo MOMP in a stress-regulated manner, a phenomenon we term "minority MOMP." Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death. Instead, this caspase activity leads to DNA damage that, in turn, promotes genomic instability, cellular transformation, and tumorigenesis. Our data demonstrate that, in contrast to its well-established tumor suppressor function, apoptosis also has oncogenic potential that is regulated by the extent of MOMP. These findings have important implications for oncogenesis following either physiological or therapeutic engagement of apoptosis., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the evidence on the validity of sacral lateral branch blocks and the effectiveness of sacral lateral branch thermal radiofrequency neurotomy in managing sacroiliac complex pain., Design: Systematic review with comprehensive analysis of all published data., Interventions: Six reviewers searched the literature on sacral lateral branch interventions. Each assessed the methodologies of studies found and the quality of the evidence presented., Outcome Measures: The outcomes assessed were diagnostic validity and effectiveness of treatment for sacroiliac complex pain. The evidence found was appraised in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system of evaluating scientific evidence., Results: The searches yielded two primary publications on sacral lateral branch blocks and 15 studies of the effectiveness of sacral lateral branch thermal radiofrequency neurotomy. One study showed multisite, multidepth sacral lateral branch blocks can anesthetize the posterior sacroiliac ligaments. Therapeutic studies show sacral lateral branch thermal radiofrequency neurotomy can relieve sacroiliac complex pain to some extent. The evidence of the validity of these blocks and the effectiveness of this treatment were rated as moderate in accordance with the GRADE system., Conclusions: The literature on sacral lateral branch interventions is sparse. One study demonstrates the face validity of multisite, multidepth sacral lateral branch blocks for diagnosis of posterior sacroiliac complex pain. Some evidence of moderate quality exists on therapeutic procedures, but it is insufficient to determine the indications and effectiveness of sacral lateral branch thermal radiofrequency neurotomy, and more research is required., (Wiley Periodicals, Inc.)

Primary malignant melanoma of penis with secondaries to the adrenal gland is rare. Here we report a case of malignant melanoma of penis in a 60 years old man who presented with intermittent gross, episodic haematuria of 11 months duration and a hard indurated pigmented fungating lesion over the glans penis. Following an initial tissue biopsy from the penile growth which revealed malignant melanoma the patient underwent partial Panectomy. Few days after recovery the patient underwent laparotomy and incisional biopsy from adrenal mass revealed metastatic malignant melanoma histopathologically.

Resistance to radiotherapy in glioblastoma (GBM) is an important clinical problem and several authors have attributed this to a subpopulation of GBM cancer stem cells (CSCs) which may be responsible for tumour recurrence following treatment. It is hypothesised that GBM CSCs exhibit upregulated DNA damage responses and are resistant to radiation but the current literature is conflicting. We investigated radioresistance of primary GBM cells grown in stem cell conditions (CSC) compared to paired differentiated tumour cell populations and explored the radiosensitising effects of the ATM inhibitor KU-55933. We report that GBM CSCs are radioresistant compared to paired differentiated tumour cells as measured by clonogenic assay. GBM CSC's display upregulated phosphorylated DNA damage response proteins and enhanced activation of the G2/M checkpoint following irradiation and repair DNA double strand breaks (DSBs) more efficiently than their differentiated tumour cell counterparts following radiation. Inhibition of ATM kinase by KU-55933 produced potent radiosensitisation of GBM CSCs (sensitiser enhancement ratios 2.6-3.5) and effectively abrogated the enhanced DSB repair proficiency observed in GBM CSCs at 24 h post irradiation. G2/M checkpoint activation was reduced but not abolished by KU-55933 in GBM CSCs. ATM kinase inhibition overcomes radioresistance of GBM CSCs and, in combination with conventional therapy, has potential to improve outcomes for patients with GBM., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

We collected Rimaleptus binucleatus from soil in the surroundings of the town of Ulsan, South Korea. Its morphology and 18S rRNA gene were studied using standard methods. This possibly widely distributed species is characterized by: (i) a size of about 170-400×20-65μm; (ii) a narrowly to cylindrically dileptid body with proboscis occupying about 30-65% of body length; (iii) two dorsal contractile vacuoles; (iv) two size groups of rod-shaped extrusomes; and (v) about 18-29 ciliary rows, 4-6 of them anteriorly differentiated into a staggered dorsal brush. Phylogenetic analyses of five new rhynchostomatian 18S rRNA gene sequences supported monophylies of the orders Tracheliida and Dileptida, but revealed that the genera Rimaleptus and Pseudomonilicaryon are polyphyletic. Monophyly of genera with two macronuclear nodules was consistently rejected, but monophylies of dileptids with many scattered macronuclear nodules and of dileptids with moniliform macronucleus and multi-rowed dorsal brush could not be excluded by statistical topology tests. Nevertheless, phylogenetic network analyses indicated considerable conflict in the phylogenetic signal provided by the 18S rRNA gene to resolve unambiguously relationships among dileptid genera., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

A new hypotrichous ciliate, Apoterritricha lutea n. g., n. sp., was discovered in a sample of a terrestrial liverwort from Korea. Its morphology was studied using detailed in vivo observation and protargol impregnation. Its phylogenetic relationships were revealed by analyses of the 18S rRNA gene. This new taxon is characterized by a combination of the following traits: (i) ellipsoidal to narrowly ellipsoidal body with an average size of 230 × 85 μm; (ii) two macronuclear nodules and two to five micronuclei; (iii) golden yellow cortical granules, forming small groups along the microtubular appendages of cirri, adoral membranelles, and dorsal kineties; (iv) typically three frontal cirri, one buccal cirrus, four frontoventral cirri, seven midventral cirri, two pretransverse cirri, seven transverse cirri, ca. 38 left, and ca. 36 right marginal cirri; and (v) on average six dorsal kineties, three dorsomarginal kineties, and three caudal cirri. In molecular phylogenies, A. lutea clusters with strong support within a clade containing Afrokeronopsis aurea and several "typical" oxytrichids having golden yellow to brown cortical granules. In this light we propose a hypothesis that is not unambiguously rejected by the present phylogenetic analyses, which shows how the Afrokeronopsis-like pattern could have evolved from a Rubrioxytricha-like ancestor via an Apoterritricha-like stage by cirri-multiplication., (© 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.)

The ciliate class Heterotrichea is defined by somatic dikinetids bearing postciliodesmata, by an oral apparatus consisting of a paroral membrane and an adoral zone of membranelles, as well as by features of nuclear division involving extramacronuclear microtubules. Although phylogenetic interrelationships among heterotrichs have been analyzed several times, deeper nodes of the heterotrichean tree of life remain poorly resolved. To cast more light on the evolutionary history of heterotricheans, we performed phylogenetic analyses of multiple loci (18S rRNA gene, ITS1-5.8S rRNA-ITS2 region, and 28S rRNA gene) using traditional tree-building phylogenetic methods and statistical tree topology tests as well as phylogenetic networks, split spectrum analysis and quartet likelihood mapping. This multifaceted approach has shown that (1) Peritromus is very likely an adelphotaxon of all other heterotrichs; (2) Spirostomum and Anigsteinia are sister taxa and their common monophyletic origin is strongly supported by a uniquely posteriorly-thickened paroral membrane; (3) the monotypic family Chattonidiidae should be suppressed because its type genus clusters within the family Condylostomatidae; and (4) new families are needed for Gruberia and Fabrea because their affiliation with Spirostomidae and Climacostomidae, respectively, is not supported by molecular phylogenies nor the fine structure of the paroral membrane., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study was done to determine the effects and outcome of inhaled budesonide in addition to standard management of asthma exacerbations in pediatric age groups. A randomized, double-blind, placebo controlled trial was done in a tertiary care urban hospital. Sixty six children aged 5 to 15 years with moderate to severe asthma exacerbations were eligible. All patients received a single dose of prednisolone 1mg/kg orally as first dose of systemic corticosteroids and then salbutamol (0.15mg/kg) and ipratropium bromide (500mcg) was nebulized every 20 minutes for 3 doses and then hourly for 2 hours as a part of standard treatment of asthma exacerbations. The intervention was 2mg (4mL) of budesonide or 4mL of normal saline which was nebulized immediately after the 1st dose of nebulized salbutamol and ipratropium bromide. The baseline characteristics of the budesonide group (n=33) and placebo group (n=33) were similar, but at 1 hour, 2 hour and 3 hour PEFR, respiratory rate, pulse rate, SaO2 and asthma score were significantly improved in the budesonide group compared to placebo group (p<0.01). The positive immediate effect of nebulized budesonide added to standard treatment of asthma exacerbations is an encouraging finding for further investigations of its routine use in the treatment of asthma exacerbations in children.

Background: The advent of high-resolution computed tomography scanning and increase in use of chest imaging for high-risk patients has led to an increase in the identification of small pulmonary nodules. The ability to locate and remove these nodules through a thoracoscopic approach is difficult. The purpose of this study is to report our experience with fiducial localization and percutaneous thoracoscopic wedge resection of small pulmonary nodules., Methods: This is a retrospective analysis of our patients who underwent computed tomography-guided fiducial localization of pulmonary nodules. Nodules were identified with intraoperative fluoroscopy and removed by thoracoscopic wedge resection., Results: Sixty-five nodules were removed in 58 patients. Removal was successful in 98% of patients (57 of 58); 79% of the nodules (53 of 65) were cancers; 20% of these were primary lung cancers of which 9 were pure ground-glass opacities. Mean size of the nodules was 9.9 ± 4.6 mm (range, 3 to 24 mm). Mean depth from visceral pleural surface was 18.7 ± 12 mm (range, 2 to 35 mm). Mean procedure time was 58.7 ± 20.1 minutes (range, 30 to 120), and mean length of stay was 2 days (range, 1 to 6). Complications occurred in 3 patients and included fiducial embolization, fiducial migration, and parenchymal hematoma., Conclusions: Fiducial localization facilitates identification and removal of small pulmonary nodules and alleviates the need for direct nodule palpation. As shown by our series, thoracoscopic wedge resection with fiducial localization is an accurate and efficient technique. This method provides a standardized means by which to resect small and deep pulmonary nodules or ground-glass opacities., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We discovered a new haptorian ciliate, Chaenea mirabilis sp. n., in brackish water collected near the town of Busan, Korea. Its morphology was studied using standard taxonomical methods and its phylogenetic relationships were assessed by phylogenetic analysis of the 18S rRNA gene. Chaenea mirabilis is distinguished from all congeners by the combination of the following traits: (i) a narrowly bursiform to flask-shaped, 60-100 μm long body; (ii) 11-21 doughnut-shaped or sometimes horseshoe-shaped macronuclear nodules; (iii) two types of extrusomes: type I is rod-shaped and 6-8 μm long, while type II is narrowly to broadly teardrop-shaped and only 1.5-2 μm long; (iv) highly refractive special granules tightly arranged between the first and second brush row, forming a conspicuous bulge; and (v) 12-13 somatic kineties. In the 18S rRNA gene phylogeny, C. mirabilis clustered with full support with other congeners. However, there was no statistical support for classification of Chaenea into the families Fuscheriidae, Acropisthiidae, or Trachelophyllidae, but a sister relationship with the Lacrymariidae could not be excluded. Therefore, we establish a new family, Chaeneidae, within the order Lacrymariida. This affiliation is strongly corroborated by the distinctly subapical dorsal brush bearing cilium-like bristles., (© 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.)

A 4 year 7 month-old girl of consanguineous parents presented with only fever for 25 days but no cough or respiratory distress. Ches x-ray showed bilateral diffuse nodulo-striate opacities in both lungs. Investigations for any infection were negative including tuberculosis. Thoracoscopic biopsy showed alveolar microliths on histopathology suggesting the diagnosis of pulmonary alveolar microlithiasis (PAM).

In vivo experimental models of hepatocellular carcinoma (HCC) that recapitulate the human disease provide a valuable platform for research into disease pathophysiology and for the preclinical evaluation of novel therapies. We present a variety of methods to generate subcutaneous or orthotopic human HCC xenografts in immunodeficient mice that could be utilized in a variety of research applications. With a focus on the use of primary tumor tissue from patients undergoing surgical resection as a starting point, we describe the preparation of cell suspensions or tumor fragments for xenografting. We describe specific techniques to xenograft these tissues i) subcutaneously; or ii) intrahepatically, either by direct implantation of tumor cells or fragments into the liver, or indirectly by injection of cells into the mouse spleen. We also describe the use of partial resection of the native mouse liver at the time of xenografting as a strategy to induce a state of active liver regeneration in the recipient mouse that may facilitate the intrahepatic engraftment of primary human tumor cells. The expected results of these techniques are illustrated. The protocols described have been validated using primary human HCC samples and xenografts, which typically perform less robustly than the well-established human HCC cell lines that are widely used and frequently cited in the literature. In comparison with cell lines, we discuss factors which may contribute to the relatively low chance of primary HCC engraftment in xenotransplantation models and comment on technical issues that may influence the kinetics of xenograft growth. We also suggest methods that should be applied to ensure that xenografts obtained accurately resemble parent HCC tissues.

Ethyl cellulose (EC) polymer was characterized for its property before considering the interactions with the plasicizer. Ethocel Std.10 FP Premium from Dow chemical company USA was tested for its solubility, morphology and thermal properties. Seven percentage of EC solution in ethanol was found to be the right viscosity used to prepare the film. The EC polymer and EC film without any plasticizers showed almost identical thermal behavior, but in X-ray diffraction showed different arrangements of crystallites and amorphous region. Dynamic mechanical analysis of film showed that without a plasticizer, EC film was not flexible and had very low elongation with high applied force. The aim of the work was to avoid using the commercially available EC dispersions Surelease® and Aquacoat®; both already have additives on it. Instead, Ethocel EC polymer (powder) was characterized in our laboratory in order to find out the properties of polymer before considering the interactions of the polymer with various plasticizers.

Management of infected non-union following fracture of a long bone is a challenge to the orthopaedic surgeon. Several methods of treating these cases have been described.(1-7) Although reports of single stage or multiple stage procedures exist in the literature, general consensus appears to favour a two-stage approach with initial debridement followed by the use of local antibiotic cement in the first stage.(2,5,8) This antibiotic-impregnated cement has been reported in previous papers as placed around an intramedullary nail or via antibiotic cement beads,(4-6,9) Cement beads offer no mechanical stability to the fracture site. Placing cement around an intramedullary device provides added concerns, such as cement nail debonding and the continued presence of metal, which could cause persistence of infection when in contact with endosteal sequestrate. We describe the use of an antibiotic cement nail fashioned by hand intra-operatively around a length of nylon tape. This eliminates the need for further metalwork during the infected stage, thereby reducing the chance of persistent non-union as well as providing some stability across the fracture site.

The association between thyroid autoimmunity and thyroid cancer was carried out in a series of solitary thyroid nodules submitted to fine-needle aspiration cytology and subsequent histopathology. US guided FNACs were obtained from 295 unselected consecutive patients with single thyroid nodules and positive (98) or negative (197) serum anti-thyroid antibody. Cytological results were classified in three classes of increased risk of malignancy: low risk (class II); indeterminate risk (class III); and suspect or malignant (class IV). A higher prevalence of class III (29.6%, p<0.05) and class IV (17.34%, p<0.05) and lower prevalence of class II (52.06%, p<0.01) were found in ATA+ nodules respectively. By multivariate logistic regression analysis ATA+ conferred a significant risk (odds ratio: 1.97 & 95% confidence interval: 0.97-3.97) for class IV cytology independently for age and sex. In 53 patients where thyroidectomy was carried out, thyroid cancer was found in (86.66%) patients with class IV nodules, in (19.4%) of class III nodules (all ATA-) and in none of 7 class II nodules. Histologically proven thyroid cancer (mostly papillary) was then observed in a higher proportion (13.2%) of ATA+, when compared with ATA- nodules (8.1%, p>0.01), but the significance of this finding is limited by the low number of class II nodules operated on. The presence of ATA+ confers an increased risk of suspicious or malignant cytology in solitary thyroid nodules.

Ninety six percent of patients with overlooked bile duct stones required surgery within 5 years of cholecystectomy, every effort should be made to keep the incidence of retained stones minimum. The facilities of pre-operative ERCP are not always available. Examination of the bile ducts under direct vision with a choledochoscope seems a certain method of ensuring that there are no residual stone. A total of 26 patients were evaluated between the periods of 2004 to 2005. Age of the patients ranged from 20 to 70 years. The mean age is about 45.88 years approximately. Six (23.07%) cases had previous history of cholecystectomy. Peroperatively 14(53.84%) cases had only choledocholithiasis, 6(23.07%) cases had cholelithiasis with choledocholithiasis, 4(15.38%) cases had choledocholithiasis with hepatolithiasis and 2(7.69%) cases had Mirrizi's type II with choledocholithiasis. After Choledochoscopy, 22(84.61%) cases had complete blind clearance, 4(15.38%) cases had incomplete blind clearance. Twenty two (84.61%) cases did not require any Choledochoscopy guided stone extraction. Four (15.38%) cases required Choledochoscopy guided Dormia basket extraction. Twenty two (84.61%) cases have undergone T tube drainage, 4(15.38%) cases undergone Roux-en-Y hepaticojejunostomy who had associated hepatolithiasis. In this series percentage of stone overlooked by instrumental exploration was 15.38 & percentage of residual stone in this study was 0%.