Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.

PURPOSE: The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. METHODS: We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. RESULTS: Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59 years (range, 27-90 years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50 years had a 47.1% likelihood of pN+ disease. CONCLUSION: Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.

Antiproliferative effect of Solanum nigrum L. water extract on breast can-cer cells: potential roles of apoptosis and oxidative stress.

Breast cancer is the most progressive cancer among women worldwide. The currently available chemotherapeutic agents induce severe unacceptable adverse effects in breast cancer patients. In this context, natural medicinal herbs are gaining importance to find non-toxic effective anticancer drugs. Solanum nigrum is one of the major traditional medicinal plants widely used in Ayurveda for the treatment of various diseases. This study investigated the anticancer effect of Solanum nigrum water extract (SNWE) against MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines. SNWE significantly induced oxidative stress-mediated apoptotic cell death in a concentration-dependent manner. Real-time PCR results illustrated the upregulation of proapoptotic genes and downregulation of antiapoptotic genes after SNWE treatment in MCF-7 and MDA-MB-231 cell lines. Immunofluorescence analysis showed increased expressions of apoptotic markers like p53, Caspase3 and BAX by SNWE treatment. In conclusion, the findings of this study indicate the antiproliferative effect and apoptosis-inducing property of SNWE in both cell lines. Further studies are warranted on testing the anticancer activity of S. nigrum L. using animal models of cancer.

Evaluation of use of hyperbaric oxygen in suppression of hyper-proliferation in hypoxic NSCLC cells.

Hyperbaric oxygen therapy (HBO) is being researched as a potential adjuvant treatment for solid malignancies, such as NSCLC. It can reduce tumour hypoxia and has been found to slow tumour growth, stop dedifferentiation, and reduce apoptosis resistance in hypoxic NSCLC cells. Though HBO has shown promise in treating various cancers, more study is required to determine its precise mechanism of action in NSCLC. Analyze the effect of hyperbaric oxygen on the growth of hypoxic non-small cell lung cancer cells. We used the NSCLC cell lines A549 and H1299 to analyze aerobic glycolysis in vitro. Warburg effect testing included glucose absorption, lactate, adenosine triphosphate (ATP), and pyruvate measurements. Using a quantitative glycolytic flow model, we also analyzed the effect of HIF-1-induced genes on the flux of glucose metabolism. Lewis lung carcinoma (LLC) animal models in C57BL/6J mice were used to examine the development of lung tumours. The effects of pcDNA and HIF1A on glucose uptake, lactate production, pyruvate, and ATP levels were studied in A549 and H1299 NSCLC cells. While A549's glucose absorption increased over time, H1299's was dramatically decreased by HBO treatment. The pyruvate levels were more significant in H1299, particularly in hypoxia, and were lowered by HBO. In A549, the lactate content was more effective. After HBO treatment, glucose absorption was reduced while intracellular ATP levels were maintained. Overexpression of HIF-1a was able to counteract the effect of HBO on glycolytic gene expression. PFKP is a possible therapeutic target because HBO reduces the Warburg effect in NSCLC cells by downregulating HIF-1.

Laparoscopic sleeve gastrectomy for obesity treatment in adolescents and young adults: a systematic review and meta-analysis.

BACKGROUND: The incidence of obesity has been increasing in younger population, posing a significant impact on adolescents' life and health care system worldwide. METHODS: We critically analyzed the existing literature on the use of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity. We performed an in-depth evaluation of 37 studies and analyzed the effect of LSG in 2300 patients, aged ≤ 22 years. RESULTS: Mean body mass index (BMI) loss after LSG was 17.81 kg/m2. Gastroesophageal reflux was the most common complication. Most of the patients showed remission of comorbidities including hypertension, diabetes, and obstructive sleep apnea after LSG. CONCLUSIONS: These findings suggest that surgical intervention is highly beneficial for reducing BMI in appropriately selected adolescents and young adults suffering from obesity and comorbidities such as life-threatening obstructive sleep apnea.

Serum Levels of Proinflammatory Biomarkers in Military Recruits with and without Metabolic Syndrome.

Objectives: Inflammatory mediators are associated with many chronic diseases; however, their role in metabolic syndrome (Met-S) is not well documented. We therefore aimed to compare the serum markers of inflammation including C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and TNF-ß in young military recruits with and without Met-S. We hypothesized that any significant change in inflammatory markers between the two groups would indicate the role of inflammation in Met-S that would help in future directions for screening and treatment of Met-S. Design and Methods. A total of 2010 adult men, aged 18-30 years, were divided into two groups: with Met-S (N = 488) and without Met-S (N = 1522), according to the International Diabetes Federation definition. We compared the serum levels of inflammatory biomarkers between the two groups. We also studied the correlations between the inflammatory markers and the components of Met-S to explore the biomarker potential of inflammatory markers for screening of Met-S. Logistic regression analysis was performed to test the association between inflammatory markers and Met-S. Results: A large number of subjects in the Met-S group were suffering from obesity. Out of the 2010 total subjects, only 731 (36.4%) had normal fasting blood sugar (FBS), while the prevalence of prediabetes and diabetes was significantly higher in subjects with Met-S. We observed significant increases in serum levels of CRP, MPO, IL-6, and TNF-ß but not TNF-α in subjects with Met-S as compared to subjects without Met-S. All the markers of inflammation showed significant correlations with Met-S, triglycerides (TG), blood pressure, body mass index (BMI), and age; however, none of these markers were correlated with HDL. Logistic regression analysis showed a significant association between Met-S and inflammatory markers. Conclusions: Serum levels of CRP, MPO, IL-6, and TNF-ß are significantly increased in young adults with Met-S. This is probably the first study reporting TNF-ß levels in Met-S. Since a proinflammatory cascade precedes many years before the onset of cardiovascular disease, these inflammatory biomarkers could help in the monitoring of high-risk individuals with Met-S who will be requiring therapeutic intervention.

Fault Classification for Cooling System of Hydraulic Machinery Using AI.

Hydraulic systems are used in all kinds of industries. Mills, manufacturing, robotics, and Ports require the use of Hydraulic Equipment. Many industries prefer to use hydraulic systems due to their numerous advantages over electrical and mechanical systems. Hence, the growth in demand for hydraulic systems has been increasing over time. Due to its vast variety of applications, the faults in hydraulic systems can cause a breakdown. Using Artificial-Intelligence (AI)-based approaches, faults can be classified and predicted to avoid downtime and ensure sustainable operations. This research work proposes a novel approach for the classification of the cooling behavior of a hydraulic test rig. Three fault conditions for the cooling system of the hydraulic test rig were used. The spectrograms were generated using the time series data for three fault conditions. The CNN variant, the Residual Network, was used for the classification of the fault conditions. Various features were extracted from the data including the F-score, precision, accuracy, and recall using a Confusion Matrix. The data contained 43,680 attributes and 2205 instances. After testing, validating, and training, the model accuracy of the ResNet-18 architecture was found to be close to 95%.

Early Identification of Crop Type for Smallholder Farming Systems Using Deep Learning on Time-Series Sentinel-2 Imagery.

Climate change and the COVID-19 pandemic have disrupted the food supply chain across the globe and adversely affected food security. Early estimation of staple crops can assist relevant government agencies to take timely actions for ensuring food security. Reliable crop type maps can play an essential role in monitoring crops, estimating yields, and maintaining smooth food supplies. However, these maps are not available for developing countries until crops have matured and are about to be harvested. The use of remote sensing for accurate crop-type mapping in the first few weeks of sowing remains challenging. Smallholder farming systems and diverse crop types further complicate the challenge. For this study, a ground-based survey is carried out to map fields by recording the coordinates and planted crops in respective fields. The time-series images of the mapped fields are acquired from the Sentinel-2 satellite. A deep learning-based long short-term memory network is used for the accurate mapping of crops at an early growth stage. Results show that staple crops, including rice, wheat, and sugarcane, are classified with 93.77% accuracy as early as the first four weeks of sowing. The proposed method can be applied on a large scale to effectively map crop types for smallholder farms at an early stage, allowing the authorities to plan a seamless availability of food.

Smartphone addiction in medical students: Association with perceived stress, personality factors and loneliness.

Background: Smartphone addiction (SMA) is an emerging concept. It has been associated with high perceived stress. There is a dearth of data on its association with loneliness and personality in the Indian context. Objectives: We planned this study to estimate the prevalence of SMA in medical students, verify its reported association with perceived stress, and determine its association with personality factors and loneliness. Methods: Four hundred and two medical students participated in this cross-sectional study. We used the SMA scale-short version to divide students into those having an addiction and not having an addiction. The Perceived Stress Scale, ten-item personality inventory, and University of California, Los Angeles Loneliness Scale were used to assess perceived stress, personality, and loneliness. Ninety-five percent confidence intervals were reported for all comparisons. Results: The prevalence of SMA in medical students was 34.8%. SMA was associated with higher perceived stress and loneliness. Students having SMA scored lower on personality domains of extraversion, agreeableness, conscientiousness, emotional stability, and openness to experience. Moreover, SMA interfered with students' social life and academic performance. Conclusions: SMA is a cause for concern. We need to plan the awareness campaigns focusing on SMA and its association with social life and academic performance. Researchers need to explore this concept in larger samples and diverse population groups to know its actual magnitude and impact. Moreover, dedicated psychiatric committees need to recommend the guidelines for the judicious use of smartphones.

Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging.

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.

Safety and outcomes of thrombolytic therapy in patients with pulmonary embolism and thrombocytopenia: A systematic review.

Thrombolysis is an established therapeutic modality for patients with high-risk (and some selected intermediate-risk) pulmonary embolism (PE) with hemodynamic instability. Physicians sometimes experience cases where both a high-risk PE and thrombocytopenia coexist. Although thrombocytopenia of <  100 × 103/mm3 is considered a contraindication in patients with ischemic stroke, the safety and outcomes of thrombolysis in patients with acute PE and thrombocytopenia are unknown. This systemic review aimed to pool data on the safety and outcomes of thrombolysis use in patients with PE and platelet count less than 150 × 103/mm3. Patients' demographics, clinical characteristics, management, type of thrombolytic therapy, and outcomes were extracted and analyzed. Of 283 articles identified through the systematic search, 11 case reports fulfilled the inclusion criteria. The mean age of the patients was 52.27 years, and 54.5% were women. The median platelet level before thrombolysis was 65.50 × 103/mm3. Before thrombolysis was initiated, the lowest and highest platelet levels were 29 × 103/mm3 and 105 × 103/mm3, respectively. Alteplase was used in 10 patients and urokinase in one patient. One patient who had a massive PE died of aspiration pneumonia. Interestingly, no thrombocytopenia-related complications were reported. This systematic review highlights the potential benefits and safety of thrombolysis in patients with acute PE in the context of thrombocytopenia. Nevertheless, data available in the literature concerning this topic are scarce and limited to case reports. More extensive studies on the use of thrombolysis in patients with PE and thrombocytopenia are desperately needed. Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42021286415.

Pro-Apoptotic and Immunotherapeutic Effects of Carbon Nanotubes Functionalized with Recombinant Human Surfactant Protein D on Leukemic Cells.

Nanoparticles are efficient drug delivery vehicles for targeting specific organs as well as systemic therapy for a range of diseases, including cancer. However, their interaction with the immune system offers an intriguing challenge. Due to the unique physico-chemical properties, carbon nanotubes (CNTs) are considered as nanocarriers of considerable interest in cancer diagnosis and therapy. CNTs, as a promising nanomaterial, are capable of both detecting as well as delivering drugs or small therapeutic molecules to tumour cells. In this study, we coupled a recombinant fragment of human surfactant protein D (rfhSP-D) with carboxymethyl-cellulose (CMC) CNTs (CMC-CNT, 10-20 nm diameter) for augmenting their apoptotic and immunotherapeutic properties using two leukemic cell lines. The cell viability of AML14.3D10 or K562 cancer cell lines was reduced when cultured with CMC-mwCNT-coupled-rfhSP-D (CNT + rfhSP-D) at 24 h. Increased levels of caspase 3, 7 and cleaved caspase 9 in CNT + rfhSP-D treated AML14.3D10 and K562 cells suggested an involvement of an intrinsic pathway of apoptosis. CNT + rfhSP-D treated leukemic cells also showed higher mRNA expression of p53 and cell cycle inhibitors (p21 and p27). This suggested a likely reduction in cdc2-cyclin B1, causing G2/M cell cycle arrest and p53-dependent apoptosis in AML14.3D10 cells, while p53-independent mechanisms appeared to be in operation in K562 cells. We suggest that CNT + rfhSP-D has therapeutic potential in targeting leukemic cells, irrespective of their p53 status, and thus, it is worth setting up pre-clinical trials in animal models.

Design of expert guided investigation of native L-asparaginase encapsulated long-acting cross-linker-free poly (lactic-co-glycolic) acid nanoformulation in an Ehrlich ascites tumor model.

Present study explores native L-asparaginase encapsulated long-acting cross-linker-free PLGA-nanoformulation in an Ehrlich ascites tumor model. L-asparaginase-PLGA nanoparticles for tumor were prepared using a double emulsion solvent evaporation technique, optimized and validated by Box-Behnken Design. L-ASN-PNs showed a particle size of 195 nm ± 0.2 nm and a PDI of 0.2. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques revealed its smooth morphology and elicited an in-vitro release of 80% of the drug, following the Higuchi drug release model. In-vivo studies of L-ASN-PNs on an Ehrlich ascites tumor (EAT) model were completed and compared with the standard medication of 5-fluorouracil (5-FU) treatment. L-ASN-PN treated mice showed a 51.15% decrease in tumor volume and 100% survival rate with no reduction in body weight, no haemotoxicity and no hepatotoxicity, as evident from the hematological parameters, and liver enzyme parameters that were well within the prescribed limits. Chemotherapy has severe side effects and restricted therapeutic success. Henceforth, the purported L-Asparaginase PLGA nanoparticles are a suitable entity for better tumor regression, intra-tumor accumulation and no hematological side-effects.

DNA methylation signatures of breast cancer in peripheral T-cells.

BACKGROUND: Immune surveillance acts as a defense mechanism in cancer, and its disruption is involved in cancer progression. DNA methylation reflects the phenotypic identity of cells and recent data suggested that DNA methylation profiles of T cells and peripheral blood mononuclear cells (PBMC) are altered in cancer progression. METHODS: We enrolled 19 females with stage 1 and 2, nine with stage 3 and 4 and 9 age matched healthy women. T cells were isolated from peripheral blood and extracted DNA was subjected to Illumina 450 K DNA methylation array analysis. Raw data was analyzed by BMIQ, ChAMP and ComBat followed by validation of identified genes by pyrosequencing. RESULTS: Analysis of data revealed ~ 10,000 sites that correlated with breast cancer progression and established a list of 89 CG sites that were highly correlated (p < 0.01, r > 0.7, r < - 0.7) with breast cancer progression. The vast majority of these sites were hypomethylated and enriched in genes with functions in the immune system. CONCLUSIONS: The study points to the possibility of using DNA methylation signatures as a noninvasive method for early detection of breast cancer and its progression which need to be tested in clinical studies.

Correction to: GLP-I Secretion in Healthy and Diabetic Wistar Rats in Response to Aqueous Extract of Momordica charantia.

Following publication of the original article [1], the authors reported that there was an error in the acknowledgements. In this Correction, the incorrect and correct acknowledgements are shown.

GLP-I secretion in healthy and diabetic Wistar rats in response to aqueous extract of Momordica charantia.

BACKGROUND: Diabetes mellitus is one of the major global health disorders increasing at an alarming rate in both developed and developing countries. The objective of this study was to assess the effect of aqueous extract of Momordica charantia (AEMC) on fasting blood glucose (FBG), tissue glycogen, glycosylated haemoglobin, plasma concentrations of insulin and GLP-1 hormone (glucagon-like peptide 1) in healthy and diabetic wistar rats. METHODS: Male Wistar rats (both normal and diabetic) were treated with AEMC by gavaging (300 mg/kg body wt/day for 28 days). RESULTS: AEMC was found to increase tissue glycogen, serum insulin and GLP-1 non-significantly (P > 0.05) in normal, significantly (P < 0.01) in diabetic Wistar rats, whereas decrease in FBG and Glycosylated haemoglobin non-significantly (P > 0.05) in normal, significantly (P < 0.01) in diabetic Wistar rats. The elevation of GLP-1 level in normal and diabetic treated groups may be due to the L-cell regeneration and proliferation by binding with L-cell receptors and makes a conformational change, resulting in the activation of a series of signal transducers. The polar molecules of M. charantia also depolarize the L-cell through elevation of intracellular Ca2+ concentration and which in turn releases GLP-1. GLP-1 in turn elevates beta-cell proliferation and insulin secretion. CONCLUSION: The findings tend to provide a possible explanation for the hypoglycemic action of M. charantia fruit extracts as alternative nutritional therapy in the management and treatment of diabetes.

Correction to: GLP-I secretion in healthy and diabetic Wistar rats in response to aqueous extract of Momordica charantia.

Following publication of the original article [1], the authors reported that there was an error in the acknowledgements.

Histopathology of the Liver, Kidney, and Spleen of Mice Exposed to Gold Nanoparticles.

Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections with a gap of one week) of 5 nm, 20 nm, and 50 nm diameter GNPs on the structural and biochemical changes in the liver, kidney, and spleen of mice. The results showed that small sized GNPs (5 nm) produced significant pathological changes in the liver on day 2 that gradually reduced on day 8. The medium (20 nm) and large (50 nm) sized GNPs preferentially targeted the spleen and caused significant pathological changes to the spleen architecture on day 2 that persisted on day 8 as well. There were minimal and insignificant pathological changes to the kidneys irrespective of the GNPs size. The animals that were primed with the pre-exposure of GNPs did not show any aggravation of histological changes after the second dose of the same GNPs. None of the dose regimens of the GNPs were able to significantly affect the markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) in all of the organs that were studied. In conclusion, the size of GNPs plays an important role in their pathological effects on different organs of mice. Moreover, the primed animals become refractory to further pathological changes after the second dose of GNPs, suggesting the importance of a priming dose in medical applications of GNPs.

The Association Between Physical activity with Cognitive And Cardiovascular Deconditioning In Age Related Decline Of College Students.

OBJECTIVE: To determine the association between physical activity and cognition in age-related decline of college students and to find the correlation between physical activity with cardiovascular deconditioning. METHODS: The analytical cross-sectional study was conducted from January 1 to May 1, 2017, in different medical and engineering colleges of Rawalpindi and Islamabad in Pakistan.Data was collected through non-probability purposive sampling method. Demographic data was recorded and standardized assessment tools, including physical activity index and stroop colour word test for cognition, were used. Bivariate correlation analysis was used to determine association between different variables. RESULTS: Of the 702 subjects, 340(48.5%) were males and 362(51.7%) were females. The overall mean age was 21.84±1.73 years (range: 17-24 years), and mean body mass index was 22.12±3.6.Overall, 292 (41.8%) students were labelled as physically active and 410(58.8%) had sedentary lifestyle.Physical activity and cognition showed positive association (p=0.004) in students.Physically inactive participants showed cardiovascular and cognitive deconditioning with age (p = 0.68). CONCLUSIONS: Physical activity was found to be a key tool of cardiovascular health and cognition.It ameliorated overall health and brought better academic performance of students engaged in sports-related activities.

Presentation of parathyroid adenoma with genu valgum and thoracic deformities.

Parathyroid adenoma is the main cause of primary hyperparathyroidism. It is usually asymptomatic and occurs more commonly in adults. It presents with raised parathormone (PTH) and Ca+ levels in serum. Its presentation in adolescence is rare. We report one such incidence of a 14 years old girl who presented with bone pains short stature, and generalized muscle wasting. She was found to have genu valgum at the knee joint, pectus carniatum, scoliosis and cystic changes in pelvis and calvarium. Biochemical investigations and parathyroid Tc-99mMIBI scan confirmed the diagnosis of a parathyroid adenoma. The gland was removed by parathyroidectomy. Till date 12 such cases are reported and none had thoracic, vertebral or calvarium involvement.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. FROM THE CLINICAL EDITOR: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.