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We present the case of a 20-year-old male who underwent successful surgical correction of pectus excavatum with the Highly Modified Ravitch Repair (HMRR). At 29 months the attempted operative removal of the Ravitch bar was unsuccessful despite the impression of adequate bar location on chest x-ray. Subsequent imaging with computed tomography was unclear in determining whether the bar was supra or infra-diaphragmatic due to the tissue distortion subsequent to initial surgery. Video assisted thoracoscopic surgery (VATS) successfully retrieved the bar and revealed that it was not in the thorax, but had migrated to the intra-abdominal bare area of the liver, with no evidence of associated diaphragmatic defect or hernia. Intra-abdominal pectus bar migration is a rare clinical entity, and safe removal can be facilitated by the use of the VATS technique. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade has been used to treat breast cancer, but the clinical responses remain relatively poor. We have used the CRISPR-Cas9 kinome knockout library consisting of 763 kinase genes to identify tumor-intrinsic kinases conferring resistance to anti-PD-1 immune checkpoint blockade. We have identified the CDC42BPB kinase as a potential target to overcome the resistance to anti-PD-1 immune checkpoint blockade immunotherapy. We found that CDC42BPB is highly expressed in breast cancer patients who are non-responsive to immunotherapy. Furthermore, a small-molecule pharmacological inhibitor, BDP5290, which targets CDC42BPB, synergized with anti-PD-1 and enhanced tumor cell killing by promoting T cell proliferation in both in vitro and in vivo assays. Moreover, anti-PD-1-resistant breast cancer cells showed higher expression of CDC42BPB, and its inhibition rendered the resistant cells more susceptible to T cell killing in the presence of anti-PD-1. We also found that CDC42BPB phosphorylated AURKA, which in turn upregulated PD-L1 through cMYC. Our results have revealed a robust link between tumor-intrinsic kinase and immunotherapy resistance and have provided a rationale for a unique combination therapy of CDC42BPB inhibition and anti-PD-1 immunotherapy for breast cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: Human immunodeficiency virus (HIV) infection is a major public health problem. These patients are at an increased risk for end-stage kidney disease. Both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) are the accepted modalities of treatment., Materials and Methods: In this retrospective study, we included all HIV-positive end-stage kidney disease (ESKD) patients who were on dialysis - HD or CAPD - for at least 1 month. Data were collected from the dialysis charts and analyzed., Results: There were 20 patients in the CAPD group and 76 patients in the HD group. Mean age was 49.6 ± 8.73 years in the CAPD group and 46.28 ± 9.02 years in the HD group. Hypertension and diabetes were the common causes for ESKD. Mean survival was slightly better in CAPD group (20.94 vs. 15.46 months). The HD group had higher mortality within 12 months of dialysis initiation, and infection was the cause for early deaths. Mean infection episodes was 2.1 in HD group and 3.1 in CAPD group. CAPD patients with low albumin (<2.5 g/dl) had higher peritonitis rates., Conclusion: Managing HIV-positive dialysis patients remains challenging. In our study, survival was marginally better in the CAPD group. In both groups, low CD4 count was associated with more infections and low albumin with more peritonitis episodes. A study incorporating more peritoneal dialysis (PD) patients, longer follow-ups, and a matched non-HIV control will throw more light on patient outcomes., Competing Interests: There are no conflicts of interest., (© 2024 Indian Journal of Nephrology | Published by Scientific Scholar.)

Dendritic cells (DCs) play critical roles in recognizing and presenting antigens to T cells. They secrete dendritic cell-derived extracellular vesicles (DC-sEVs), which could mimic the function of DCs. Therefore, we explore the possibility of using DC-sEVs as a potential personalized vaccine in this study. We compared the efficacy of DCs and DC-sEVs on stimulating the immune system to target breast cancer cells and found that DC-sEVs had significantly more MHC molecules on the surface when compared to the parental DCs. In our in vivo and in vitro testing, Dc-sEVs showed significant advantages over DCs, regarding efficacy, safety, storage, and potential delivery advantages. DC-sEVs were able to suppress the growth of immune-cold breast tumors, while DCs failed to do so. These results indicate the strong potential utility of DC-sEVs as a personalized immunotherapy for breast cancer., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Breast cancer has been shown to be resistant to immunotherapies. To overcome this challenge, we developed an active immunotherapy for personalized treatment based on a smart nanovesicle. This is achieved by anchoring membrane-bound bioactive interleukin 2 (IL2) and enriching T cell-promoting costimulatory factors on the surface of the dendritic cell-derived small extracellular vesicles. This nanovesicle also displays major histocompatibility complex-bound antigens inherited from tumor lysate-pulsed dendritic cell. When administrated, the surface-bound IL2 is able to guide the nanovesicle to lymphoid organs and activate the IL2 receptor on lymphocytes. Furthermore, it is able to perform antigen presentation in the replacement of professional antigen-presenting cells. This nanovesicle, named IL2-ep13nsEV, induced a strong immune reaction to rescue 50% of the mice in our humanized patient-derived xenografts, sensitized cancer cells to immune checkpoint inhibitor treatment, and prevented the recurrence of resected tumors. This paradigm presents a feasible strategy for the treatment and prevention of metastatic breast cancer.

Background: Ductal carcinoma in situ (DCIS) of breast is the noninvasive lesion that has propensity to progress to the malignant form. At present, it is still unknown which lesions can potentially progress to invasive forms. In this study, we aimed to identify key lncRNAs involved in DCIS growth., Methods: We employ disease-related lncProfiler array to identify IPW in specimens of DCIS and matching control samples and validate the observations in three DCIS-non-tumorigenic cell lines. Further, we examine the mechanism of IPW action and the downstream signaling in in vitro and in vivo assays. Importantly, we screened a library containing 390 natural compounds to identify candidate compound selectively inhibiting IPW low DCIS cells., Results: We identified lncRNA IPW as a novel tumor suppressor critical for inhibiting DCIS growth. Ectopic expression of IPW in DCIS cells strongly inhibited cell proliferation, colony formation and cell cycle progression while silencing IPW in primary breast cells promoted their growth. Additionally, orthotropic implantation of cells with ectopic expression of IPW exhibited decreased tumor growth in vivo. Mechanistically, IPW epigenetically enhanced miR-29c expression by promoting H3K4me3 enrichment in its promoter region. Furthermore, we identified that miR-29c negatively regulated a stemness promoting gene, ID2, and diminished self-renewal ability of DCIS cells. Importantly, we screened a library containing 390 natural compounds and identified toyocamycin as a compound that selectively inhibited the growth of DCIS with low expression of IPW, while it did not affect DCIS with high IPW expression. Toyocamycin also suppressed genes associated with self-renewal ability and inhibited DCIS growth in vivo., Conclusion: Our findings revealed a critical role of the IPW-miR-29c-ID2 axis in DCIS formation and suggested potential clinical use of toyocamycin for the treatment of DCIS., (© 2022. The Author(s).)

Bone metastasis is an incurable complication of breast cancer. In advanced stages, patients with estrogen-positive tumors experience a significantly higher incidence of bone metastasis (>87%) compared to estrogen-negative patients (<56%). To understand the mechanism of this bone-tropism of ER + tumor, and to identify liquid biopsy biomarkers for patients with high risk of bone metastasis, the secreted extracellular vesicles and cytokines from bone-tropic breast cancer cells are examined in this study. Both exosomal miR-19a and Integrin-Binding Sialoprotein (IBSP) are found to be significantly upregulated and secreted from bone-tropic ER + breast cancer cells, increasing their levels in the circulation of patients. IBSP is found to attract osteoclast cells and create an osteoclast-enriched environment in the bone, assisting the delivery of exosomal miR-19a to osteoclast to induce osteoclastogenesis. Our findings reveal a mechanism by which ER + breast cancer cells create a microenvironment favorable for colonization in the bone. These two secreted factors can also serve as effective biomarkers for ER + breast cancer to predict their risks of bone metastasis. Furthermore, our screening of a natural compound library identifies chlorogenic acid as a potent inhibitor for IBSP-receptor binding to suppress bone metastasis of ER + tumor, suggesting its preventive use for bone recurrence in ER + patients., (© 2021. The Author(s).)

Background: Brain metastasis of breast cancer exhibits exceedingly poor prognosis, and both triple negative (TN) and Her2 + subtypes have the highest incidence of brain metastasis. Although estrogen blockers are considered to be ineffective for their treatment, recent evidence indicates that estrogen blockade using tamoxifen showed certain efficacy. However, how estrogen affects brain metastasis of triple negative breast cancer (TNBC) remains elusive., Methods: To examine the effect of estrogen on brain metastasis progression, nude mice were implanted with brain metastatic cells and treated with either estrogen supplement, tamoxifen, or ovariectomy for estrogen depletion. For clinical validation study, brain metastasis specimens from pre- and post-menopause breast cancer patients were examined for microglia polarization by immunohistochemistry. To examine the estrogen-induced M2 microglia polarization, microglia cells were treated with estrogen, and the M1/M2 microglia polarization was detected by qRT-PCR and FACS. The estrogen receptor-deficient brain metastatic cells, SkBrM and 231BrM, were treated with conditioned medium (CM) derived from microglia that were treated with estrogen in the presence or absence of tamoxifen. The effect of microglia-derived CM on tumor cells was examined by colony formation assay and sphere forming ability., Results: We found that M2 microglia were abundantly infiltrated in brain metastasis of pre-menopausal breast cancer patients. A similar observation was made in vivo, when we treated mice systemically with estrogen. Blocking of estrogen signaling either by tamoxifen treatment or surgical resection of mice ovaries suppressed M2 microglial polarization and decreased the secretion of C-C motif chemokine ligand 5, resulting in suppression of brain metastasis. The estrogen modulation also suppressed stemness in TNBC cells in vitro. Importantly, estrogen enhanced the expression of signal regulatory protein α on microglia and restricted their phagocytic ability., Conclusions: Our results indicate that estrogen promotes brain metastasis by skewing polarity of M2 microglia and inhibiting their phagocytic ability, while tamoxifen suppresses brain metastasis by blocking the M2 polarization of microglia and increasing their anti-tumor phagocytic ability. Our results also highlight a potential therapeutic utility of tamoxifen for treating brain metastasis of hormone receptor-deficient breast cancer.

Smoking has a profound impact on tumor immunity, and nicotine, which is the major addictive component of smoke, is known to promote tumor progression despite being a non-carcinogen. In this study, we demonstrate that chronic exposure of nicotine plays a critical role in the formation of pre-metastatic niche within the lungs by recruiting pro-tumor N2-neutrophils. This pre-metastatic niche promotes the release of STAT3-activated lipocalin 2 (LCN2), a secretory glycoprotein from the N2-neutrophils, and induces mesenchymal-epithelial transition of tumor cells thereby facilitating colonization and metastatic outgrowth. Elevated levels of serum and urine LCN2 is elevated in early-stage breast cancer patients and cancer-free females with smoking history, suggesting that LCN2 serve as a promising prognostic biomarker for predicting increased risk of metastatic disease in female smoker(s). Moreover, natural compound, salidroside effectively abrogates nicotine-induced neutrophil polarization and consequently reduced lung metastasis of hormone receptor-negative breast cancer cells. Our findings suggest a pro-metastatic role of nicotine-induced N2-neutrophils for cancer cell colonization in the lungs and illuminate the therapeutic use of salidroside to enhance the anti-tumor activity of neutrophils in breast cancer patients.

Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.

Up to 40% of lung cancer patients develop brain metastasis, and the median survival of these patients remains less than 6 months. Smoking is associated with lung cancer. However, how smoking impacts the development of brain metastasis remains elusive. We examined 281 lung cancer patients with distant metastasis and found that smokers exhibited a significantly high incidence of brain metastasis. We found that nicotine enhanced brain metastasis, while a depletion of microglia suppressed this effect in vivo. Nicotine skewed the polarity of microglia to the M2 phenotype, thereby increasing the secretion of IGF-1 and CCL20, which promoted tumor progression and stemness. Importantly, nicotine enhanced the expression of SIRPα in microglia and restricted their phagocytic ability. We also identified a compound, parthenolide, that suppressed brain metastasis by blocking M2 polarization. Our results indicate that nicotine promotes brain metastasis by skewing the polarity of M2 microglia, which enhances metastatic tumor growth. Our results also highlight a potential risk of using nicotine for tobacco cessation., Competing Interests: Disclosures: Dr. Shiozawa reported grants from Teva Pharmaceutical Industries outside the submitted work. Dr. Chan reported other from Elekta and other from Monteris outside the submitted work. No other disclosures were reported., (© 2020 Wu et al.)

Background: Low grade gliomas (LGG) are most often noted with the unpredictable overall survival and progression to higher grades. Objective: In the present study, we analyze the clinicopathological features influencing the prognostic outcomes and compared the features with criteria developed by EORTC., Materials and Methods: We observed the 130 LGG clinical cases in single institute and maintained the follow-up for more than 5 years. In addition, the molecular details were confirmed with markers as IDH, 1p/19q codeletion, p53 and ATRX mutations., Results: The mean age of patients as 37.67 years and male population contributing to 70%. We observed biased incidence among the male population with dominating occurrence at frontal and parietal lobes in the brain. 40.8% patients had oligodendroglioma, 33.8% astrocytoma, 19.2% oligoastrocytoma and 2.3% gemistocytic astrocytoma pathology. Patients who were subjected to chemotherapy and radiotherapy were noted with average survival of 29 months. Oligodendroglial tumors were found with progression free survival (PFS) of 25 months, oligoastrocytoma cases with 32 months, diffuse astrocytoma cases with 23 months while the gemistocytic astrocytoma cases had 22 months. The PFS for LGG cases was 4.7 years while the overall survival was 4.9 years. Mean survival of patients with KPS score <70 and >70 was 1.5 & 4.9 years respectively. 64 patients were observed with the tumor size >5 cm. In total, 72.3% of the patients were underwent GTR, 23.3% STR and 3.8% underwent biopsy., Conclusion: Taken together, the clinical symptoms, expression of molecular markers and the prognosis details provided by our results can help for better management of LGG cases. We further propose to use following five factors to accurately describe the prognosis and tumor recurrence: 1) Age >50 years, 2) tumor size >5 cm, 3) MIB index >5%, 4) KPS score < 70 and 5) gemistocytic pathology., Competing Interests: None

Astrocytoma constitutes the most noted malignancies of the central nervous system with worse clinical outcomes in grade IV astrocytoma or glioblastoma multiforme. Owing to poor clinical outcomes with existing therapeutic regime, there is a need to revisit the initial course of treatment. Statistical information of clinicopathological parameters could be used to understand the spread of disease and, in turn, to formulate updated treatment management. In the present study, we have seen anatomic distribution of astrocytoma subtypes in a group of 479 patients and correlated it with survival outcomes. Anatomic location was confirmed by MRI (magnetic resonance imaging) images. A registry of patients was maintained with clinicopathological details as tumor type, location, age/sex, and survival after surgery. We have observed overall survival particulars in patients diagnosed with astrocytoma. Our findings highlight that in total cases, tumor location was anatomically dominated by frontal and temporal lobes. Survival analysis in high-grade (grade III, p  = 0.03; grade IV, p  = 0.01) astrocytic tumors confirms poor outcomes with temporal, parietal, and occipital location as compared to frontal lobe. Overall survival study demonstrates glioblastoma multiforme (GBM) was associated with worse prognosis as compared to astrocytoma subtypes ( p  < 0.0001). In high-grade astrocytomas, anaplastic astrocytoma was found with 34 months of median survival age while 14 months in the case of patients with glioblastoma multiforme. In conclusion, we report dismal prognosis in parietal, temporal, and occipital lobes in grade II, grade III, and grade IV astrocytoma patients. Among astrocytoma subtypes, patients with glioblastoma multiforme were associated with worse survival outcomes. We uniquely feature the survival of astrocytoma patients for the first time and observe GBM patients have slightly longer survival., Competing Interests: The authors declare that they have no conflict of interest.The present studies involving human participants were approved by the Institutional Ethics Committee (ICE), University of Hyderabad and KIMS Foundation Research Centre (KFRC), KIMS, Secunderabad, India. All subjects participating were completely anonymized.Informed consent was obtained from all individual participants included in the study.

Objectives: Astrocytoma represents most noted malignancy of the brain. The overall survival rate of patients with progressive form remains dismal despite of the present clinical advancements. Search for biomarkers can open new avenues of therapeutic measures to curb the progressive astrocytic tumors. Nck1 is reported to be involved in actin cytoskeleton rearrangement and neuronal migration. Here, we have determined prognostic importance of Nck1 protein in astrocytoma progression. Temporal lobe epilepsy tissues were used as control., Methods: Real time PCR was used to analyze Nck1 transcript expression while western blotting and immunohistochemistry techniques were used to study expression on translational levels. Protein expression in western blots was categorized as Nck1 positive and Nck1 negative. We further seen the prognostic significance of Nck1 in 246 glioblastoma tissue samples as visible from the TCGA database., Results: We find Nck1 RNA and protein was upregulated significantly in high grade tissues as compared to low grade and control tissue samples (p < 0.05). Logrank test and Kaplan-Meier analysis signified the use of Nck1 as independent prognostic marker for astrocytoma progression and its expression levels were correlated with poor survival in surgically resected human tissue samples (Chi square = 10.7, p = 0.001). Further, glioblastoma was noticed to be predominant at frontal and temporal lobe., Conclusion: On account of it's over expression, Nck1 appears as possible biomarker for astrocytoma progression and may serve as an important therapeutic target. Prominent origin of glioblastoma at frontal and temporal lobe suggests possible involvement of tissue specific developmental or transcriptional factors in origin of tumors.

Astrocytoma is recognized as the most common neoplasm of the brain with aggressive progression. The therapeutic regime for glioblastoma, the most aggressive astrocytoma, often consists of aggressive chemo and radiotherapy. The present holistic approaches, however, have failed to influence the quality life of patients. Therefore, it is necessary to understand the underlying mechanisms of its progression for updated therapeutic evaluation. Human cytomegalovirus (HCMV) is reported to be associated with glioblastoma progression. The hypothesis still remains controversial due to the lack of concrete evidences. Here, we report the profile of miRNAs encoded by human host and the cytomegalovirus (CMV) involved in modulation of CMV infection in surgically resected human astrocytoma tissue samples of various malignancy grades (n = 24). Total RNA from the control brain and tumor tissues was extracted by TriZol reagent. The expression levels of the mature form of miRNA were detected by real-time PCR. Primarily, we found the upregulation of miR-210-3p, miR-155-5p, miR-UL-112-3p, miR-183-5p, and miR-223-5p in high-grade astrocytic tumors as compared with low-grade tumor tissues. miR-214-3p is significantly expressed in control brain tissues and its expression decreased with astrocytoma grade progression. This miRNA was reported to be associated with antiviral proprieties. Among CMV-encoded miRNA, miR-UL-112-3p was significantly upregulated in glioblastoma tissue samples and may be involved in providing immune escape to the virus as well as involved in modulating the immune microenvironment of glioblastoma. Taken together, we conclude the possible involvement of miRNAs in modulating the CMV dependent astrocytoma progression.

Background: Nitidine chloride (NC) is known to exert anticancer and anti-metastatic effects on a variety of tumors. Recently, NC has also been shown to inhibit PIK3/AKT/mTOR axis in U87 human glioma cells., Methods: The study shows NC employing pDok2, caspase 3 dependent cell death in C6 rat glioma and U87 human malignant glioblastoma cells. The effect of NC on glioblastoma cell lines was accessed by MTT, clonogenic and wound healing assays. Cell cycle analysis was performed by FACS. Moreover, the effect of NC on downstream target proteins, such as caspase3, pDok2, PARP, and Gsk3 beta, were measured by western blotting., Results: Overexpressed pDok2 protein has recently been reported as a prognostic marker with poor outcomes for human glioblastoma multiformae. We found that NC inhibits pDok2 in U87 cells in a concentration-dependent way. We further showed that cleaved PARP and cleaved caspase 3 protein expressions were increased in C6 cells treated with NC in a dose-dependent way. NC effectively attenuated C6 cells growth and colony formation at 8μM (micromoles) concentration. Cell cycle arrest in G2/M phase was further confirmed by flow cytometry. NC also exhibited its inhibitory effect on Gsk3 beta, which has been proven to be altered in glioma biology., Conclusions: Collectively, we predicted that NC could be employed as a potential anti-glioma mediator that needs attention to explore the mechanisms of its activity., (Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Astrocytoma is the most frequent malignancies of the brain. Despite present clinical advancements, median survival time in malignant forms remains poor. Downstream of kinase protein 2 (Dok2) is adaptor protein known to modulate the effect of tyrosine kinase. Previously, Dok2 is shown to be marker of poor prognosis in colorectal and gastric cancer, and reduced levels of Dok2 were reported in lung adenocarcinoma and gastric cancer. The aim of the present study was to evaluate prognostic significance of pDok2 expression in surgically resected astrocytoma tissue samples. In the present study, 47 numbers of tissue samples were collected from patients who underwent surgery for astrocytoma. Temporal lobe epilepsy tissues were used as control. Real-time PCR was used to study transcript expression while protein expression was studied by western blotting and immunohistochemistry. The pDok2 expression was categorized as pDok2 positive and pDok2 negative on the basis of intensity of protein expression. This observation was confirmed by two independent pathologists. Control and few GII tissues were used as reference on account for low expression of pDok2 protein. Basic information of patients as anatomic origin of tumor and follow-up details were retrieved from hospital registry. Kaplan-Meier test was used to analyze the association of pDok2 expression and survival outcome in clinical cases. Real-time PCR signifies pDok2 is overexpressed in high-grade (GIII + GIV) tissue samples compared with low-grade (GII) and control brain tissue samples (p < 0.005). Western blotting and immunohistochemistry analysis signifies overexpression of pDok2 protein expression in tumor tissue samples as compared with control brain tissues. Clinico-pathological analysis reveals 83% of high-grade astrocytoma (GIII + GIV) and 30% of low-grade (GII) tissue samples which were detected with pDok2 expression. Tumor location was found to be predominant at the frontal and temporal lobes. Survival studies underline prognostic importance of pDok2 protein. Median survival of 20 months was reported with patients with positive pDok2 expression (95% CI 0.083 to 0.49). Taken together, pDok2 protein overexpression is associated with poor prognosis in astrocytoma clinical cases and appears to be an attractive target for therapeutic intervention. Noticeable anatomic origin at the frontal and temporal lobe suggests site-specific role of developmental factors in tumor occurrence.

Astrocytomas are the most common brain tumors with poor survival in malignant forms. Signal regulatory protein alpha (SIRP alpha) is a transmembrane protein expressed on immune cells and macrophages and is reported to modulate tumor cell phagocytosis. In the present study, we investigated the involvement of miR-520d-5p and miR-520d-3p in regulation of SIRP alpha expression. Here, we report mRNA and protein expression profile of SIRP alpha in 39 surgically resected human astrocytoma tissue samples and 14 control brain tissue samples. Transcript expression pattern was studied by real-time PCR while Western blotting and immunohistochemistry were used to evaluate protein expression. Expression profile of miR-520d-5p and miR-520d-3p was studied by real-time PCR. Computational prediction was employed to analyze the binding of miR-520d-5p and miR-520d-3p for SIRP alpha mRNA. It is evident from preliminary investigation that SIRP alpha transcripts are expressed in control brain tissues, increased in low-grade (grade II) tumor tissues, and decreased with further grade progression (P < 0.05). SIRP alpha protein was moderately expressed in control brain tissues but under-expressed in low- and high-grade tissue samples (P < 0.05). Immunohistochemistry results further confirmed Western blot outcomes. Computational prediction supplemented with 3' and 5'UTR targeting analysis and correlation studies reveals that hsa-miR-520d-5p (P = 0.028, R 2  = 0.94) (95 % CI 0.15 to 0.99) and hsa-miR-520d-3p (P = 0.027, R 2  = 0.94) (95% CI 0.17 to 0.99) may be the putative microRNAs involved in regulation of SIRP alpha protein expression. Real-time PCR expression profile depicts that mature form of both miRNAs is significantly overexpressed in low-grade (GII) tumor tissue samples compared to control and high-grade (GIII and GIV) tissue samples. MiR-520d-5p and miR-520d-3p were found with expression pattern similar to SIRP alpha transcripts. We show that SIRP alpha protein is under-expressed in low and high grades of astrocytoma patients' tissue samples. Control brain tissues were found to be positive with SIRP alpha protein expression. Real-time PCR expression analysis confirms that miR-520d-5p and miR-520d-3p expression levels were significantly correlated with SIRP alpha transcripts in control, low-grade, and high-grade tissue samples. Computational prediction further evidenced for binding sites of these miRNAs on 3' and 5'UTR of SIRP alpha transcripts. Taken together, we predict that miR-520d-5p and miR-520d-3p may be having role in the regulation of under-expressed SIRP alpha protein expression.

We report an unusual case of a 61-year-old woman with group B Streptococcus-positive infective endocarditis and a left ventricular-right atrium or Gerbode's defect. We discuss the issues surrounding such an infection and the implications of such a rare cardiac defect in our case report., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The clinical environment is becoming increasingly dominated by information technology, most recently the smartphone with its applications (apps) of a multitude of uses. There are already tens of thousands of medical apps available for download, to educate both patients and trainees, and many more are being designed to facilitate delivery of care. The rapid development of this technology has outgrown its quality evaluation and regulation, both urgently required to maintain patient safety, protect sensitive data, and ensure dissemination of accurate information. We review medical apps themed towards cardiothoracic surgery in terms of medical professional involvement in their content and design., Methods: iTunes and Play Store were searched for cardiothoracic surgery-themed medical apps, using the terms cardiothoracic, thoracic, cardiac, heart, lung, surgery, and variations thereof and including the term medical., Results: A focused search yielded 379 apps, of which 6% were associated with a named medical professional, 15% with a publisher or professional society, and 63% with a user rating., Conclusions: The findings suggest inadequate input from the medical profession. The article discusses the pressing issues regarding quality evaluation, regulation, and information security, required for smartphones and handheld devices to become an integral and safe part of delivery of care., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Inappropriate or excessive use of topical corticosteroids can lead to cutaneous and systemic adverse effects which occur more commonly with the use of very potent steroids. Monitoring and analysis of the prescription practices of topical steroids can help to achieve rational prescription of these drugs., Aim: The present study was carried out to study and analyze the pattern of prescribing topical corticosteroids among outpatients attending the dermatology clinic in a rural tertiary care and teaching hospital, Ambajogai, Maharashtra., Materials and Methods: A cross-sectional descriptive study was conducted for a duration of two months from August 2011 to September 2011, and 500 prescriptions were randomly collected from the dermatology pharmacy and analyzed., Results: About 66% of the prescriptions contained four to five drugs per prescription. Topical steroids were given in 28.4% of all the prescriptions. In almost all the prescriptions, strength, quantity of the steroid to be used, frequency, site, and duration of application was not mentioned. The chief complaints and diagnoses were not mentioned in about 85% of the prescriptions for topical corticosteroids. About 94.36% of the prescriptions contained very potent steroids., Conclusion: Inadequate prescribing information is a clear characteristic of the dermatological prescriptions containing topical corticosteroids. Doctors should be educated about the importance of giving patients sufficient information regarding the use of steroids. There is a need to revise hospital formulary where low-potency steroids can also be included along with potent ones so that the latter can be avoided in conditions where they are unnecessary.

Objectives: The study was carried out with the aim of evaluation of the adverse drug reaction profile of anti-snake venom serum (ASV) in a rural tertiary care hospital., Methods: An observational study was conducted in SRTR Medical College, Ambajogai, Maharashtra, India. A total number of 296 indoor case papers of snake bite from February to September 2011 and June to August 2012 were retrieved from the record section and the antivenom reactions were assessed. In addition, basic epidemiological data and prescribing practices of ASV were also analyzed., Results: Vasculotoxic snake bites were more common (50.61%) than neuroparalytic ones (22.56%). Mild envenomation was the commonest presentation. A total of 92 (56.10%) patients who received ASV suffered from antivenom reactions. The most common nature of reaction was chills, rigors (69.56%) followed by nausea and vomiting (34.8%). 10-15% patients suffered from moderate to severe reactions like hypotension and sudden respiratory arrest. We did not find any dose response relationship of ASV to risk of reactions (odds ratio 0.37). Intradermal sensitivity test was performed in about 72% cases., Conclusion: Our study showed a higher incidence of reactions to ASV at our institute.

Objective: Operating in a day surgery unit has potential benefits, including lower risk of cancellation, reduced infection rates, cost effectiveness and increased patient satisfaction. We believe that we are the first unit in the UK to regularly perform thoracic surgery in a dedicated day surgery unit, and describe our experience to date., Methods: Data were collected prospectively from 1 September 2007 to 31 December 2009. Following surgery, patients were observed in a recovery area for 1h before transfer back to a short-stay ward. When chest drains were used, they were attached to an ambulatory drainage device for the patient to be discharged with. All patients were reviewed postoperatively, and were discharged home within 4-6h if appropriate., Results: Ninety-eight patients underwent thoracic surgery in our day surgery unit. Sixty (61.2%) patients were male. The mean age was 53.0 (17-83) years. There were no deaths. Twenty-nine (29.6%) were mediastinal procedures (MED group) such as mediastinoscopy/otomy, 31 (31.6%) were video-assisted thoracoscopic surgery (VATS group) procedures such as lung biopsies and pleurodeses and 38 (38.8%) were a variety of other (OTHER group) procedures such as chest wall interventions and sternal wire removal. Out of the cohort, three (3.1%) patients required admission directly from the day surgery unit, and three (3.1%) were admitted late after discharge with problems relating to their surgery. Our Day Surgery Programme accounted for 12.0% of the total thoracic workload during the time period., Conclusions: Surgeons are continually trying to fast track increasingly complex procedures and, with good patient selection, thoracic surgery can be performed safely and effectively in day surgery units., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study is to report our 9 years' experience with endoscopic cardiac tumor resection using the port access approach., Methods: From March 1997 to December 2005, 27 patients (mean age, 56.2 +/- 16.9 years; 70% female) underwent endoscopic cardiac tumor resection using endocardiopulmonary bypass and endoaortic-balloon clamp technique. Nineteen (70%) patients presented in New York Heart Association class I, 4 patients presented with embolic stroke, and 4 patients presented with atrial arrhythmias. All patients underwent echocardiography on admission, intraoperatively, at discharge, and at follow-up evaluation. Eight patients additionally required mitral valve replacement (n = 1), tricuspid valve replacement (n = 1), mitral valve repair (n = 2), mini-maze (n = 1), and closure of patent foramen ovale (n = 3). Mean follow-up was 3.4 +/- 2.7 years., Results: Mean endoaortic-balloon clamp and endocardiopulmonary bypass times were 68.8 +/- 30.8 minutes and 112.2 +/- 41.5 minutes, respectively. There were no conversions to sternotomy. Tumors resected were classified as left atrial myxoma (n = 20), right atrial myxoma (n = 3), lipoma (n = 1), intravenous leiomyoma involving the inferior vena cava and the tricuspid valve (n = 1), plexiform tumor of the sinoatrial node (n = 1), and papillary fibroelastoma of aortic valve noncoronary cusp (n = 1). There were no hospital deaths. Mean intensive care unit and hospital stays were 1.4 +/- 1.1 days and 7.3 +/- 3.4 days, respectively. Postoperative complications were evolving stroke (n = 1), re-exploration for bleeding (n = 1), and myocardial ischemia requiring stenting (n = 1). Follow-up failed to demonstrate residual or recurrent tumor. One patient had a small residual atrial septal defect. Ninety-two percent of patients appreciated the cosmetic result and fast recovery., Conclusions: Endoscopic cardiac tumor resection is feasible and a valid oncologic approach with an attractive cosmetic advantage over median sternotomy.

[reaction: see text] An efficient asymmetric synthesis of the vasopeptidase inhibitor BMS-189921 was accomplished. Two short enantioselective syntheses of the common key intermediate (S)-alpha-aminoazepinone 6b were developed. Olefin 3 was converted to 6b via asymmetric hydrogenation. Alternatively, enyne 12 was converted to racemic alpha-aminoazepinone 15b, which was transformed to 6b by a practical dynamic resolution.

The radial artery continues to enjoy resurgence in popularity as a conduit for coronary artery bypass grafting but few studies have examined the prevalence of preexisting disease in this vessel. We highlight a potential, avoidable pitfall when use of the radial artery for coronary artery bypass grafting is proposed.

We report the first case of AIDS-associated Kaposi's Sarcoma in a 35 year old Indian female, a commercial sex worker, with lesions involving skin and mucous membranes. Diagnosis was confirmed on histopathology, electron microscopy, seropositivity, (ELISA and Western Blot) as well as Pepti-LAV test and viral culture. Antibodies to human immunodeficiency virus, both HIV-1 & 2, were present. HLA DR5,7 was positive on oligotyping. Genetic predisposition, therefore, may be suspected.