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Chemo brain, a constellation of cognitive deficiencies followed by chemotherapy drugs, used to treat different types of cancers and adversely impacts the quality of life of a cancer survivor. The underlying mechanism of chemo brain remains vague, thus delaying the advancement of efficient treatments. Unfortunately, there is no US FDA approved medicine for chemo brain and often medicines considered for chemo brain are already the ones approved for other diseases. Nevertheless, researches exploring stem cell transplantation in different neurodegenerative diseases demonstrate that cellular transplantation could reverse chemotherapy-induced chemo brain. This review talks about the mechanism behind the cognitive impairments instigated by different chemotherapy drugs used in cancer treatment, and how stem cell therapy could be advantageous to overcome this disease.

White matter damage persists in hypoxic-ischemic newborns even when treated with hypothermia. We have previously shown that intraventricular delivery of human glial progenitors (GPs) at the neonatal stage is capable of replacing abnormal host glia and rescuing the lifespan of dysmyelinated mice. However, such transplantation in the human brain poses significant challenges as related to high-volume ventricles and long cell migration distances. These challenges can only be studied in large animal model systems. In this study, we developed a three dimensional (3D)-printed model of the ventricular system sized to a newborn pig to investigate the parameters that can maximize a global biodistribution of injected GPs within the ventricular system, while minimizing outflow to the subarachnoid space. Bioluminescent imaging and magnetic resonance imaging were used to image the biodistribution of luciferase-transduced GPs in simple fluid containers and a custom-designed, 3D-printed model of the piglet ventricular system. Seven independent variables were investigated. The results demonstrated that a low volume (0.1 mL) of cell suspension is essential to keep cells within the ventricular system. If higher volumes (1 mL) are needed, a very slow infusion speed (0.01 mL/min) is necessary. Real-time magnetic resonance imaging demonstrated that superparamagnetic iron oxide (SPIO) labeling significantly alters the rheological properties of the GP suspension, such that, even at high speeds and high volumes, the outflow to the subarachnoid space is reduced. Several other factors, including GP species (human vs. mouse), type of catheter tip (end hole vs. side hole), catheter length (0.3 vs. 7.62 m), and cell concentration, had less effect on the overall distribution of GPs. We conclude that the use of a 3D-printed phantom model represents a robust, reproducible, and cost-saving alternative to in vivo large animal studies for determining optimal injection parameters.

Hepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs). HepT1 cells were injected into the livers or tail veins of mice, and tumor growth was monitored with magnetic resonance and bioluminescent imaging. Blood was analyzed with fluorescence activated cell sorting to identify CTCs. Intra- and extra-hepatic tumor samples were harvested for immunohistochemistry and RNA and DNA sequencing. Cell lines were grown from tumor samples and profiled with RNA sequencing. With intrahepatic injection of HepT1 cells, 100% of animals grew liver tumors and showed vascular invasion, metastasis, and CTCs. Mutation profiling revealed genetic alterations in seven cancer-related genes, while transcriptomic analyses showed changes in gene expression with cells that invade vessels. Tail vein injection of HepT1 cells resulted in multifocal, metastatic disease. These unique models will facilitate further meaningful studies of high-risk HB.Summary StatementIn this work, we developed and thoroughly characterized several unique models of hepatoblastoma derived from the HepT1 cell line that show high-risk features.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. High-risk patients have poor survival, and current chemotherapies are associated with significant toxicities. Targeted therapies are needed to improve outcomes and patient quality of life. Most HB cases are TP53 wild-type; therefore, we hypothesized that targeting the p53 regulator Murine double minute 4 (MDM4) to reactivate p53 signaling may show efficacy. MDM4 expression was elevated in HB patient samples, and increased expression was strongly correlated with decreased expression of p53 target genes. Treatment with NSC207895 (XI-006), which inhibits MDM4 expression, or ATSP-7041, a stapled peptide dual inhibitor of MDM2 and MDM4, showed significant cytotoxic and antiproliferative effects in HB cells. Similar phenotypes were seen with short hairpin RNA (shRNA)-mediated inhibition of MDM4. Both NSC207895 and ATSP-7041 caused significant upregulation of p53 targets in HB cells. Knocking-down TP53 with shRNA or overexpressing MDM4 led to resistance to NSC207895-mediated cytotoxicity, suggesting that this phenotype is dependent on the MDM4-p53 axis. MDM4 inhibition also showed efficacy in a murine model of HB with significantly decreased tumor weight and increased apoptosis observed in the treatment group. This study demonstrates that inhibition of MDM4 is efficacious in HB by upregulating p53 tumor suppressor signaling.

This paper proposes a novel routing protocol for OppNets called MLProph, which uses machine learning (ML) algorithms, namely decision tree and neural networks, to determine the probability of successful deliveries. The ML model is trained by using various factors such as the predictability value inherited from the PROPHET routing scheme, node popularity, node's power consumption, speed, and location. Simulation results show that MLProph outperforms PROPHET+, a probabilistic-based routing protocol for OppNets, in terms of number of successful deliveries, dropped messages, overhead, and hop count, at the cost of small increases in buffer time and buffer occupancy values.

Neurological disorders are a major threat to public health. Stem cell-based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre-clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000-fold larger volume of the human brain compared to mice. Human GPs transplanted into the mouse brain migrate extensively and can induce global cell replacement, but a similar extent of migration in the human brain would only allow for local rather than global cell replacement. We review here the mechanisms that govern cell migration, which could potentially be exploited to enhance the migratory properties of GPs through cell engineering pre-transplantation. We furthermore discuss the (dis)advantages of the various cell delivery routes that are available, with particular emphasis on intra-arterial injection as the most suitable route for achieving global cell distribution in the larger brain. Now that therapeutic success has proven to be feasible in small animal models, future efforts will need to be directed to enhance global cell delivery and migration to make bench-to-bedside translation a reality.

This paper presents a Tensor Transposition Library for GPUs (TTLG). A distinguishing feature of TTLG is that it also includes a performance prediction model, which can be used by higher level optimizers that use tensor transposition. For example, tensor contractions are often implemented by using the TTGT (Transpose-Transpose-GEMM-Transpose) approach – transpose input tensors to a suitable layout and then use high-performance matrix multiplication followed by transposition of the result. The performance model is also used internally by TTLG for choosing among alternative kernels and/or slicing/blocking parameters for the transposition. TTLG is compared with current state-of-the-art alternatives for GPUs. Comparable or better transposition times for the "repeated-use" scenario and considerably better "single-use" performance are observed.

The aim of this study was to examine the allele and genotype of APOA5 -1131T/C (rs662799) and APOA5-56C/G (rs3135506) gene in acute myocardial (AMI) case and control subjects. 304 case and 304 controls were enrolled in this study. DNA was extracted using salting out method followed by polymerase chain reaction amplification and restriction endonuclease digestion (using MseI for -1131T/C and Taq1 for -56C/G). Digested PCR products were identified using agarose gel electrophoresis and stained with ethidium bromide. There was a strong association between APOA5 -1131T/C (TC vs. TT, OR= 1.58 and CC vs. TT OR= 2.43) and APOA5 -56C/G (CG vs. CC, OR= 1.64 and GG vs. CC, OR= 2.44) polymorphisms with AMI. Out of the six potential risk factors for coronary artery disease, only smoking, diabetes and hypertension were found to be associated with APOA5 gene and increased the risk of AMI. Smoking was the most prominent risk factor for both the genes. Other risk factors like history of dyslipidemia, obesity and family history of coronary artery disease did not reveal any potential association with the candidate gene. Our data demonstrate that both the SNPs in the APOA5 gene (-1131T/C, and -56C/G) were strongly associated with AMI in north Indian population.

Article history: Received on: 04/06/2015 Revised on: 19/07/2015 Accepted on: 12/08/2015 Available online: 27/09/2015 Gender differences are increasingly recognized in cardiology. It is also well known that women have higher complications and a higher mortality related to coronary procedures. In arrhythmias, gender-specific variations in the electrophysiological structure of the heart or hormonal effects may explain some of the gender differences. The aim of this study was to evaluate gender differences according to their risk factors, indications and modes of pacing. A total of 267 patients who had pacemaker implantation for bradyarrhythmia indications were enrolled in our study. A pre-designed questionnaire was filled to record their baseline characteristics, clinical indications and mode of pacing. Out of 267 patients 190 were male and 77 were female. Data was analyzed with SPSS 16.0 software (SPSS, Chicago, IL, USA) The pacemaker implantation requirement was 31% significantly lower among males compared with females who were hypertensive (RR=0.69, 95%CI=0.58-0.82, p=0.0001) and 1.57 times (RR=1.57, 95%CI=1.32-1.87, p=0.0001) significantly higher among male patients than females who were the tobacco user in any form. The single chamber requirement was 1.41 times significantly (RR=1.41, 95%CI=1.16-1.71, p=0.0001) higher in males than females. The risk analysis showed that complete heart blockage (p= 0.02) and sick sinus syndrome (p= 0.01) were significantly higher in males as compared with females. In conclusion male patients had more CHB, sick sinus syndrome and syncope as primary pacemaker indication, compared with female patients. Smoking was the most prominent risk factor in male and hypertension in female and most importantly there were significant gender differences in indications leading to pacing.

Syncope is a symptom of many underlying disease states, which range from the relatively benign to the life threatening. There are numerous investigations done for patients with recurrent unexplained syncope which may have very low yield when it comes to making a definitive diagnosis. Recently, the implantable loop recorder (ILR) for continuous monitoring of the cardiac rhythm has been launched in India. This review will briefly discuss these current availabel strategies and focus on the usefulness of an ILR in the definitive diagnosis and treatment of patients with a recurrent unexplained syncope.

Pheochromocytomas are catecholamine secreting tumors of chromaffin cells. The extra adrenal pheochromocytomas are known as paragangliomas. Paragangliomas of the urinary bladder account for less than 0.06 % of all bladder tumors [1]. It commonly presents between second to fourth decades of life. Most surgeons and anesthesiologists are unfamiliar with paraganglioma of the urinary bladder. Unsuspected paraganglioma greatly increases peroperative morbidity and mortality in patients undergoing even relatively minor surgical procedures.

Background Abnormal collagen metabolism is thought to play an important role in the development of primary inguinal and ventral hernia. The detection of an impaired collagen balance both in the tissue as well as in cultured fibroblasts underlines the suspicion that the development of hernia is likely to be implemented primarily by a disturbance of the fibroblast function and their collagen genes. Based on these results we assume that the altered collagen synthesis in hernia patients can be regarded as a genetically linked deregulation serving as a basic initiating or promoting factor for the development of primary inguinal hernias. With the hypothesis that hernia is a local manifestation of a systemic disease manifested by increased expression of matrix metallo-proteinase-2 (MMP-2), a study was planned with following aims: 1) to establish a causal association between inguinal hernia and MMP-2; 2) to test the hypothesis that hernia is a local manifestation of a systemic disorder rather than a mere local mechanical defect. Methods A case control study was conducted on 30 subjects of each direct and indirect inguinal hernia and 30 controls. DAC-ELISA test was used for analysis of serum (preoperative) and tissue samples (fascia transversalis) in patients as well as controls. Results Statistically, serum levels of MMP-2 were significantly increased in all the hernia patients as compared to controls. This increment was maximum in patients of direct hernia. MMP-2 was not detectable in tissue samples. Conclusions Hernia is a local manifestation of a systemic disease rather than a mere local mechanical defect. Keywords MMP-2; Matrix Metalloproteinase-2; Inguinal hernia; DAC-ELISA; Collagen metabolism; PBST-Phosphate Buffer Saline Tween-20

Objective: The aim of this study was to compare serum lipid profiles: total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and very low density lipoprotein cholesterol (VLDL-c) and lipid ratio among ovarian cancer (OC) patients and healthy controls. Methods: Total 300 subjects were enrolled in this study. Study group comprised of 150 clinically and histologically proved cases of ovarian carcinoma and 150 healthy women recruited as a control group. Plasma levels of TC, TG and HDL were determined using a commercially available kit and a semi-automated analyzer. LDL and VLDL were calculated by Friedewald's formula. Results: In our study, we found the higher level of mean serum cholesterol, TGs, LDL-c and VLDL in OC patients as compared to the controls. The HDL level is higher in controls as compared to study group. TGs, HDL-c VLDL were found highly significant in OC patients as compared to controls. The Ratio of TC/HDL, LDL/HDL, HDL/LDL was also found significantly higher in OC patients as compared to controls. Conclusions: The results of the present study shows that plasma lipid levels, except HDL-cholesterol, are increase in OC. As there is an alteration in the plasma lipid profile during gynecologic cancers, it may be helpful for diagnosis of the disease. Further studies needed to investigate, to group important factors including, cancer stages and type of cancer, parity, and menopausal status that may affect lipid profiles in OC patients along with an investigation of new lipid profiles to clarify most lipid factors that may involve in OC development are needed.

Background Inguinal lymph node involvement is an important prognostic factor in penile cancer. Inguinal lymph node dissection allows staging and treatment of inguinal nodal disease. However, it causes morbidity and is associated with complications, such as lymphocele, skin loss and infection. Video Endoscopic Inguinal Lymphadenectomy (VEIL) is an endoscopic procedure, and it seems to be a new and attractive approach duplicating the standard open procedure with less morbidity. We present here a critical perioperative assessment with points of technique. Methods Ten patients with moderate to high grade penile carcinoma with clinically negative inguinal lymph nodes were subjected to elective VEIL. VEIL was done in standard surgical steps. Perioperative parameters were assessed that is - duration of the surgery, lymph-related complications, time until drain removal, lymph node yield, surgical emphysema and histopathological positivity of lymph nodes. Results Operative time for VEIL was 120 to180 minutes. Lymph node yield was 7 to 12 lymph nodes. No skin related complications were seen with VEIL. Lymph related complications, that is, lymphocele, were seen in only two patients. The suction drain was removed after four to eight days (mean 5.1). Overall morbidity was 20% with VEIL. Conclusion In our early experience, VEIL was a safe and feasible technique in patients with penile carcinoma with non palpable inguinal lymph nodes. It allows the removal of inguinal lymph nodes within the same limits as in conventional surgical dissection and potentially reduces surgical morbidity.