Publications by authors named "Anita Mehta"

86 Publications

Multiple screening approaches reveal HDAC6 as a novel regulator of glycolytic metabolism in triple-negative breast cancer.

Sci Adv 2021 Jan 15;7(3). Epub 2021 Jan 15.

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer without a targeted form of therapy. Unfortunately, up to 70% of patients with TNBC develop resistance to treatment. A known contributor to chemoresistance is dysfunctional mitochondrial apoptosis signaling. We set up a phenotypic small-molecule screen to reveal vulnerabilities in TNBC cells that were independent of mitochondrial apoptosis. Using a functional genetic approach, we identified that a "hit" compound, BAS-2, had a potentially similar mechanism of action to histone deacetylase inhibitors (HDAC). An in vitro HDAC inhibitor assay confirmed that the compound selectively inhibited HDAC6. Using state-of-the-art acetylome mass spectrometry, we identified glycolytic substrates of HDAC6 in TNBC cells. We confirmed that inhibition or knockout of HDAC6 reduced glycolytic metabolism both in vitro and in vivo. Through a series of unbiased screening approaches, we have identified a previously unidentified role for HDAC6 in regulating glycolytic metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abc4897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810372PMC
January 2021

Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia.

Cancer Cell 2020 Dec 19;38(6):872-890.e6. Epub 2020 Nov 19.

Department of Medical Oncology, Dana-Farber Cancer Institute, 440 Brookline Avenue, M430, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address:

Acquired resistance to BH3 mimetic antagonists of BCL-2 and MCL-1 is an important clinical problem. Using acute myelogenous leukemia (AML) patient-derived xenograft (PDX) models of acquired resistance to BCL-2 (venetoclax) and MCL-1 (S63845) antagonists, we identify common principles of resistance and persistent vulnerabilities to overcome resistance. BH3 mimetic resistance is characterized by decreased mitochondrial apoptotic priming as measured by BH3 profiling, both in PDX models and human clinical samples, due to alterations in BCL-2 family proteins that vary among cases, but not to acquired mutations in leukemia genes. BCL-2 inhibition drives sequestered pro-apoptotic proteins to MCL-1 and vice versa, explaining why in vivo combinations of BCL-2 and MCL-1 antagonists are more effective when concurrent rather than sequential. Finally, drug-induced mitochondrial priming measured by dynamic BH3 profiling (DBP) identifies drugs that are persistently active in BH3 mimetic-resistant myeloblasts, including FLT-3 inhibitors and SMAC mimetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccell.2020.10.010DOI Listing
December 2020

Cognitive Function Assessment in Patients on Moderate- or High-Intensity Statin Therapy.

J Clin Med Res 2020 Apr 30;12(4):255-265. Epub 2020 Mar 30.

Cooper Research Institute, Cooper Medical School of Rowan University, Camden, NJ, USA.

Background: Cardiovascular diseases are the leading cause of death in the USA. Statin therapy reduces cardiovascular events significantly. Cognitive impairment has been reported with statin therapy but there is a lack of consensus. We analyzed the cognitive functions of adult patients who were on moderate-intensity statin therapy (MIST) or high-intensity statin therapy (HIST).

Methods: A total of 213 patients underwent cognitive assessment testing. Cognitive function scores were correlated with the durations of statin therapy, age, and level of education by using Pearson correlation. Independent -test was used to compare the mean cognitive function score to the gender, race, type of statin therapy, and comorbid conditions.

Results: Mean age of all the patients was 55.4 years. Majority of the patients (66.2%) were on MIST while the rest (33.8%) were on HIST. Cognitive impairment was observed in 17.8% of the studied patients. A total of 41.7% of the patients in the HIST group and 5.7% in the MIST group had cognitive impairment (P < 0.001). There was no correlation between cognitive function score and age (r = -0.106), weakly positive correlation between the level of education and cognitive function score (r = 0.252), and weakly negative correlation between the duration of statin therapy and cognitive function score (r = -0.283). In the group of patients on HIST with cognitive impairment, the proportion of patients on atorvastatin 40 - 80 mg was significantly higher than the proportion of patients on rosuvastatin 20 - 40 mg (66.7% vs. 33.3%; P < 0.05). In the group of patients on MIST with cognitive impairment, atorvastatin 10 - 20 mg was the most commonly used statin therapy (50%), followed by rosuvastatin 10 mg (25%), simvastatin 20 - 40 mg (12.5%) and pravastatin 40 - 80 mg (12.5%).

Conclusions: We found a significantly higher association of cognitive impairment in patients who were on MIST or HIST compared to the general population. We found no correlation between cognitive function score and age, weakly positive correlation between the level of education and cognitive function score, and weakly negative correlation between the duration of statin therapy and cognitive function score. HIST was associated with a higher frequency of cognitive impairment compared to the MIST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr4144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188372PMC
April 2020

Carotid intima media thickness in children with nephrotic syndrome: an observational case control study.

Sudan J Paediatr 2019 ;19(2):110-116

Department of Paediatrics, BRD Medical College, Gorakhpur, India.

Carotid intima media thickness (cIMT) is considered as a surrogate marker for the various cardiovascular events that complicate nephrotic syndrome (NS). The present work was conducted to study cIMT in children with NS and to find out its correlation with dyslipidemia and other risk factors. This was a case control study conducted at a tertiary care hospital in children with NS who were more than 2 years with normal serum complement, being on therapy for NS for at least 1 year, glomerular filtration rate more than 90 ml/minute/1.73 m and absence of acute infection in previous 3 months. Sixty six children with NS constituted the case material and 128 age and sex matched children were taken as control. The mean age in case and control cohort was 6.71 ± 3.3 and 7.89 ± 3.95 years, respectively. The mean age of onset of illness was 4.32 ± 2.25 years. The mean duration of illness was 2.39 ± 1.44 years. Thickness of cIMT was higher in NS children as compared to control group in all the ages, but this difference was statistically significant only after 4 years of age. There was statistically significant, but weak positive correlation between cIMT and age of NS children, duration of disease and number of relapses. There was no correlation of cIMT with hypertension, body mass index, serum creatinine, and dyslipidemia. A negative, but statistically insignificant correlation of cIMT was found with serum albumin and serum cholesterol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.24911/SJP.106-1535804613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962263PMC
January 2019

An experimental model of asthma in rats using ovalbumin and lipopolysaccharide allergens.

Heliyon 2019 Nov 19;5(11):e02864. Epub 2019 Nov 19.

Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.

Asthma is chronic and multi-factorial inflammatory disease hence single allergen induced asthma in an animal is not identical to clinical asthma. Therefore, we developed a novel experimental model of asthma in rats using ovalbumin (OVA) and lipopolysaccharide (LPS) allergens. Rats were divided into four groups; normal (NC), OVA, LPS, and OVA-LPS treated. Rats were sensitized with OVA (100 μg/kg, adsorbed in 100 mg/mL aluminum hydroxide, i.p.), LPS (10 μg/kg, i.p.) and both (OVA-LPS) on 7, 14, 21 days and was followed by challenge with OVA (1%w/v), LPS (1%w/v), OVA (0.5%w/v) and LPS (0.5%w/v) for 30 min thrice/week for three weeks in the OVA, LPS and OVA-LPS groups, respectively. On 41 day, lung function parameters (respiration rate, tidal volume, and airflow rate), total and differential leukocytes count in the blood as well as BALf and inflammatory cytokines (IL-4, IL-5, and IL-13) in serum were measured. Histology of lungs was performed. The results suggested that the tidal volume and airflow rate were significantly decreased while respiration rate, total and differential leukocytes count in blood as well as BALf and serum cytokines level were significantly increased in the OVA-LPS as compared to NC, OVA, and LPS. In conclusion, the combination of OVA and LPS induced phenotypes of severe asthma with eosinophilic, neutrophilic and lymphocytic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2019.e02864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872797PMC
November 2019

Spectrum and Immediate Outcome of Acute Kidney Injury in a Pediatric Intensive Care Unit: A Snapshot Study from Indian Subcontinent.

Indian J Crit Care Med 2019 Aug;23(8):352-355

Department of Pediatrics, BRD Medical College, Gorakhpur, Uttar Pradesh, India.

Background And Aims: Acute kidney injury (AKI) became an important cause of mortality and morbidity in critically ill children, despite advancement in its management. In developing countries etiology of AKI are different from that of developed countries.

Materials And Methods: This observational study was carried out in pediatric intensive care unit (PICU) in 2 months to18 years of critically ill children. Kidney injury was defined and categorized by the pRIFLE criteria.

Results: Out of 361children, 86 children (23.8%) developed AKI at some point during admission, 275 children (age and sex matched) who did not develop kidney injury during hospitalization served as non-AKI children. Maximum cases of AKI were seen in 1-5 years of age. Maximum children of AKI were of viral encephalitis (n = 43, 50.0%) followed by scrub typhus (n = 14, 16.3%). Risk factors for the development of AKI were shock, PRISM score and longer hospital stay. In our study the mortality in AKI children (n = 30, 34.8%) was significantly higher ( = 0.005) as compared to non-AKI children (n = 56, 20.3%)). Duration on mechanical ventilation, PICU stay and hospital stay were also significantly ( = 0.001) higher in AKI children.

Conclusion: AKI is common in critically ill children and associated with high mortality and morbidity.

How To Cite This Article: Bharat A, Mehta A, Tiwari HC, Sharma B, Singh A, Singh V. Spectrum and Immediate Outcome of Acute Kidney Injury in a Pediatric Intensive Care Unit: A Snapshot Study from Indian Subcontinent. Indian J Crit Care Med 2019;23(8):352-355.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5005/jp-journals-10071-23217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709838PMC
August 2019

Rituximab in kidney disease and transplant.

Animal Model Exp Med 2019 Jun 26;2(2):76-82. Epub 2019 Mar 26.

Department of Pharmacology L. M. College of Pharmacy Ahmedabad Gujarat India.

Rituximab is a chimeric monoclonal antibody that binds to CD20 antigen of B-cells. It depletes the level of mature B-cells by various mechanisms such as mediation of antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and B-cell apoptosis. Rituximab is a USFDA approved drug for clinical use in non-Hodgkin's B-cell lymphoma (NHL), rheumatoid arthritis, chronic lymphocytic leukemia (CLL), granulomatosis with polyangiitis and pemphigus vulgaris. It is also known for its "off label" use in renal disease and renal transplant worldwide. However, the exact mechanisms by which it exerts its effect in the aforementioned condition remain unclear but may be related to its long-term effects on plasma cell development and the impact on B-cell modulation of T cell responses. This review discusses the current use of rituximab in renal disease and renal transplantation, and its potential role in novel therapeutic protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ame2.12064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600632PMC
June 2019

Protective effects of Gαq-RGS2 signalling inhibitor in aminophylline induced cardiac arrhythmia.

Clin Exp Pharmacol Physiol 2019 11 16;46(11):1037-1043. Epub 2019 Aug 16.

Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.

An over activation of GPCR mediated Gαq dependent signalling pathway is widely associated with the development of cardiovascular abnormalities. The objective of study was to evaluate the effects of (1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one) Gαq-RGS2 signalling inhibitor on aminophylline induced cardiac arrhythmia in rats. Rats were divided into four groups; normal rats, disease control (DC, aminophylline treated 100 mg/kg/d, i.p., 7 days), Gαq-RGS2 signalling inhibitor (1 and 10 mg/kg/d, p.o., 7 days) treated arrhythmic rats. Gαq-RGS2 signalling inhibitor was administered 1 hour prior to the administration of aminophylline from 1st day. At the end of study, heart rate (HR), QRS complex, QT and RR interval were measured by electrocardiogram (ECG) of anesthetized rats. Systolic and diastolic blood pressure (SBP, DBP) by invasive method, cardiac damage markers (CK-MB, LDH) in the serum, antioxidant enzymes (SOD, catalase, glutathione) and cAMP level were measured. The treatment of Gαq-RGS2 signalling inhibitor (10 mg/kg) significantly abolished the aminophylline induced increase of heart rate, prolongation of RR and QT interval as compared to DC rats. Gαq-RGS2 signalling inhibitor (1 and 10 mg/kg) significantly attenuated the prolongation in QRS complex, increase of SBP, DBP and cardiac damage markers as compared to DC. Gαq-RGS2 signalling inhibitor treatment (10 mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC. Gαq-RGS2 signalling inhibitor (10 mg/kg) showed the protective effect against the aminophylline induced cardiac arrhythmia and it might be due to improvement in cAMP level and antioxidant enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1440-1681.13143DOI Listing
November 2019

Reprint of: Breast tissue markers: Why? What's out there? How do I choose?

Clin Imaging 2019 May - Jun;55:196-212. Epub 2019 Jun 14.

Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1234, New York, NY 10029, United States of America.

Tissue marker placement after image-guided breast biopsy has become a routine component of clinical practice. Marker placement distinguishes multiple biopsied lesions within the same breast, prevents re-biopsy of benign lesions, enables multi-modality correlation, guides pre-operative localization and helps confirm surgical target removal. Numerous breast tissue markers are currently available, with varied shapes, composition, and associated bio-absorbable components. This review serves to familiarize the breast interventionalist with the tissue markers most widely available in the United States today and to provide guidance regarding selection of appropriate markers for various clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinimag.2019.05.014DOI Listing
November 2019

PARP Inhibitor Efficacy Depends on CD8 T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer.

Cancer Discov 2019 06 23;9(6):722-737. Epub 2019 Apr 23.

Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8 T-cell infiltration and activation , and that CD8 T-cell depletion severely compromises antitumor efficacy. Olaparib-induced T-cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared with HR-proficient TNBC cells and models. CRISPR-mediated knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T-cell infiltration . These findings elucidate an additional mechanism of action of PARP inhibitors and provide a rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC. SIGNIFICANCE: This work demonstrates cross-talk between PARP inhibition and the tumor microenvironment related to STING/TBK1/IRF3 pathway activation in cancer cells that governs CD8 T-cell recruitment and antitumor efficacy. The data provide insight into the mechanism of action of PARP inhibitors in -associated breast cancer..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2159-8290.CD-18-1218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548644PMC
June 2019

Anti-leukemic and anti-angiogenic effects of d-Limonene on K562-implanted C57BL/6 mice and the chick chorioallantoic membrane model.

Animal Model Exp Med 2018 Dec 21;1(4):328-333. Epub 2018 Nov 21.

Department of Pharmacology L. M. College of Pharmacy Ahmedabad Gujarat India.

Background: d-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of d-Limonene on a K562-induced model of chronic myeloid leukemia (CML) in C57BL/6 mice.

Method: The tail vein injection model of K562 cells in immunocompromised C57BL/6 mice was developed and evaluated for characteristics of the disease. The mice were treated with d-Limonene and evaluated for haematological parameters. We also evaluated the effect of d-Limonene on angiogenesis using the chick chorioallantoic membrane (CAM) assay.

Results: In a complete blood count, a significant dose-dependent reduction in white blood cell, neutrophil and lymphocyte counts, but an elevation in red blood cell count and haemoglobin content was observed with d-Limonene treatment compared to the disease control or untreated group. In the CAM assay, d-Limonene produced a significant dose-dependent reduction in number of blood vessels in treatment groups compared to the vehicle-treated group.

Conclusion: These studies suggest promising anti-leukemic and anti-angiogenic effects of d-Limonene in the treatment of CML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ame2.12039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388054PMC
December 2018

A neutron tomography study: probing the spontaneous crystallization of randomly packed granular assemblies.

Sci Rep 2018 Dec 5;8(1):17637. Epub 2018 Dec 5.

Institut Laue-Langevin, 71 Avenue des Martyrs, 38000, Grenoble, France.

We study the spontaneous crystallization of an assembly of highly monodisperse steel spheres under shaking, as it evolves from localized icosahedral ordering towards a packing reaching crystalline ordering. Towards this end, real space neutron tomography measurements on the granular assembly are carried out, as it is systematically subjected to a variation of frequency and amplitude. As expected, we see a presence of localized icosahedral ordering in the disordered initial state (packing fraction ≈ 0.62). As the frequency is increased for both the shaking amplitudes (0.2 and 0.6 mm) studied here, there is a rise in packing fraction, accompanied by an evolution to crystallinity. The extent of crystallinity is found to depend on both the amplitude and frequency of shaking. We find that the icosahedral ordering remains localized and its extent does not grow significantly, while the crystalline ordering grows rapidly as an ordering transition point is approached. In the ordered state, crystalline clusters of both face centered cubic (FCC) and hexagonal close packed (HCP) types are identified, the latter of which grows from stacking faults. Our study shows that an earlier domination of FCC gives way to HCP ordering at higher shaking frequencies, suggesting that despite their coexistence, there is a subtle dynamical competition at play. This competition depends on both shaking amplitude and frequency, as our results as well as those of earlier theoretical simulations demonstrate. It is likely that this involves the very small free energy difference between the two structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-36331-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281579PMC
December 2018

Patterning the insect eye: From stochastic to deterministic mechanisms.

PLoS Comput Biol 2018 11 15;14(11):e1006363. Epub 2018 Nov 15.

Max Planck Institute for Mathematics in the Sciences, Leipzig, Germany.

While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity. In human and Drosophila eyes, photoreceptors sensitive to different wavelengths of light are distributed in stochastic patterns, and one such patterning system has been analyzed in detail in the Drosophila retina. Interestingly, some species in the dipteran family Dolichopodidae (the "long legged" flies, or "Doli") instead exhibit highly orderly deterministic eye patterns. In these species, alternating columns of ommatidia (unit eyes) produce corneal lenses of different colors. Occasional perturbations in some individuals disrupt the regular columns in a way that suggests that patterning occurs via a posterior-to-anterior signaling relay during development, and that specification follows a local, cellular-automaton-like rule. We hypothesize that the regulatory mechanisms that pattern the eye are largely conserved among flies and that the difference between unordered Drosophila and ordered dolichopodid eyes can be explained in terms of relative strengths of signaling interactions rather than a rewiring of the regulatory network itself. We present a simple stochastic model that is capable of explaining both the stochastic Drosophila eye and the striped pattern of Dolichopodidae eyes and thereby characterize the least number of underlying developmental rules necessary to produce both stochastic and deterministic patterns. We show that only small changes to model parameters are needed to also reproduce intermediate, semi-random patterns observed in another Doli species, and quantification of ommatidial distributions in these eyes suggests that their patterning follows similar rules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1006363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264902PMC
November 2018

High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.

Transl Oncol 2019 Feb 12;12(2):256-268. Epub 2018 Nov 12.

Institute of Pathology, Medical University of Graz, Graz, Austria; Department of Pathology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. Electronic address:

Background & Aims: Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, and fibrosis at late stage. Disturbance of the keratin cytoskeleton and aggregation of keratins (KRTs) are essential for MDB formation.

Methods: We analyzed livers of aged Krt18 mice that spontaneously developed in the majority of cases SH-associated HCC independent of sex. Interestingly, the hepatic lipid profile in Krt18 mice, which accumulate KRT8, closely resembles human SH lipid profiles and shows that the excess of KRT8 over KRT18 determines the likelihood to develop SH-associated HCC linked with enhanced lipogenesis.

Results: Our analysis of the genetic profile of Krt18 mice with 26 human hepatoma cell lines and with data sets of >300 patients with HCC, where Krt18 gene signatures matched human HCC. Interestingly, a high KRT8/18 ratio is associated with an aggressive HCC phenotype.

Conclusions: We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2018.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234703PMC
February 2019

Relactation in lactation failure and low milk supply.

Sudan J Paediatr 2018 ;18(1):39-47

Department of Paediatrics, Baba Raghav Das Medical College, Gorakhpur 273013, Uttar Pradesh, India.

The objective of the study was to determine the causes of lactation failure (LF), factors affecting relactation in mothers having low milk supply (LMS) and LF, and to know the success rate of relactation by proper counselling and positive support group. It was a prospective hospital-based study conducted in tertiary care referral hospital in mothers with their biological infants of less than 4 months of age, who were admitted with LF and some breastfeeding (BF) related problems. Mothers were advised for frequent BF in proper position and good attachment under supervision of trained BF experts with good support group. Lactogogue was used in few mothers. There were 64 mothers with LF and LMS, out of them 45 (70.3%) were between the age of 21-35 years. Maximum infants ( = 51, 79.69%) were below 6 weeks of age; and in 32 (78.04%) infants, artificial feeding was started within 15 days of postnatal life. Commonest cause of LF was mother's misconception of insufficient milk ( = 25, 39%). Relactation was possible in 100% mothers. Complete relactation was possible in 29 (85.29%) mothers when their age was <25 years and in 38 (86.36%) mothers when their infants age was <6 weeks. Chances of complete relactation were less, when duration of artificial feeding was more and infant was fed with bottle (62.96%). We found no difference with the use of lactogogue. Relactation was possible in 100% of mothers (may be partial) by continuous and positive support from family members and trained health workers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.24911/SJP.2018.1.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113782PMC
January 2018

Breast tissue markers: Why? What's out there? How do I choose?

Clin Imaging 2018 Nov - Dec;52:123-136. Epub 2018 Jul 6.

Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1234, New York, NY 10029, United States of America.

Tissue marker placement after image-guided breast biopsy has become a routine component of clinical practice. Marker placement distinguishes multiple biopsied lesions within the same breast, prevents re-biopsy of benign lesions, enables multi-modality correlation, guides pre-operative localization and helps confirm surgical target removal. Numerous breast tissue markers are currently available, with varied shapes, composition, and associated bio-absorbable components. This review serves to familiarize the breast interventionalist with the tissue markers most widely available in the United States today and to provide guidance regarding selection of appropriate markers for various clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinimag.2018.07.003DOI Listing
January 2019

Cover-Encodings of Fitness Landscapes.

Bull Math Biol 2018 08 12;80(8):2154-2176. Epub 2018 Jun 12.

Max Planck Institute for Mathematics in the Sciences, Inselstrasse 22, 04103, Leipzig, Germany.

The traditional way of tackling discrete optimization problems is by using local search on suitably defined cost or fitness landscapes. Such approaches are however limited by the slowing down that occurs when the local minima that are a feature of the typically rugged landscapes encountered arrest the progress of the search process. Another way of tackling optimization problems is by the use of heuristic approximations to estimate a global cost minimum. Here, we present a combination of these two approaches by using cover-encoding maps which map processes from a larger search space to subsets of the original search space. The key idea is to construct cover-encoding maps with the help of suitable heuristics that single out near-optimal solutions and result in landscapes on the larger search space that no longer exhibit trapping local minima. We present cover-encoding maps for the problems of the traveling salesman, number partitioning, maximum matching and maximum clique; the practical feasibility of our method is demonstrated by simulations of adaptive walks on the corresponding encoded landscapes which find the global minima for these problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11538-018-0451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061522PMC
August 2018

An anti-asthmatic activity of natural Toll-like receptor-4 antagonist in OVA-LPS-induced asthmatic rats.

Clin Exp Pharmacol Physiol 2018 11 25;45(11):1187-1197. Epub 2018 Jul 25.

Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, India.

Toll-like receptor-4 (TLR4) is a key component of the innate immune system and activation of TLR4 signaling has a significant role in the pathogenesis of asthma. Therefore, our objective was to identify the natural TLR4 antagonist and evaluate its activity in experimentally induced asthma. Soya lecithin origin phosphatidylcholine (soya PC) was identified as a natural TLR4 antagonist by computational study. Based on the computational study, TLR4 antagonist activity of soya PC was confirmed in in vitro lipopolysaccharide (LPS)-induced neutrophil adhesion assay. In the in vivo study, rats were sensitized with ovalbumin (OVA) (100 μg/kg, i.p.) on the 7th, 14th and 21st days and challenged intranasally with OVA (100 μg/100 μL) and LPS (10 ng/100 μL), 4 days/wk for 3 weeks. At the end of the experiment, we performed lung function parameters (respiratory rate, tidal volume, airflow rate), inflammatory cytokines (interleukin [IL]-4, IL-5, IL-13), total and differential leukocytes in blood as well as bronchoalveolar lavage fluid (BALf) and histological examinations. The computational study indicated that TLR4 antagonist activity of soya PC is due to linoleic acid (18:2) fatty acid chain. Soya PC significantly suppressed the LPS-induced neutrophil adhesion in a concentration-dependent manner to 1 μg/mL. The treatment of soya PC (5 and 10 mg/kg, 18 days, i.p.) significantly improved the lung function parameters, total and differential leukocyte counts in blood and BALf in asthmatic rats. This efficacy of soya PC was in extent similar to dexamethasone (2.5 mg/kg, 18 days, i.p.). However, soya PC was superior to dexamethasone in terms of benefits. The protective action of soya PC may be due to TLR4 antagonist activity and linoleic acid composition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1440-1681.13002DOI Listing
November 2018

Gamma Imaging-Guided Minimally Invasive Breast Biopsy: Initial Clinical Experience.

AJR Am J Roentgenol 2018 Mar 11;210(3):695-699. Epub 2018 Jan 11.

1 Department of Radiology, Breast Imaging and Interventional Center, The George Washington University, 2300 M St NW, Washington, DC 20037.

Objective: The purpose of this study was to evaluate our initial experience with gamma imaging-guided vacuum-assisted breast biopsy in women with abnormal findings.

Materials And Methods: A retrospective review of patients undergoing breast-specific gamma imaging (BSGI), also known as molecular breast imaging (MBI), between April 2011 and October 2015 found 117 nonpalpable mammographically and sonographically occult lesions for which gamma imaging-guided biopsies were recommended. Biopsy was performed with a 9-gauge vacuum-assisted device with subsequent placement of a titanium biopsy site marker. Medical records and pathologic findings were evaluated.

Results: Of the 117 biopsies recommended, 104 were successful and 13 were canceled. Of the 104 performed biopsies, 32 (30.8%) had abnormal pathologic findings. Of those 32 biopsies, nine (28.1%) found invasive cancers, six (18.8%) found ductal carcinoma in situ (DCIS), and 17 (53.1%) found high-risk lesions. Of the 17 high-risk lesions, there were three (17.6%) lobular carcinomas in situ, five (29.4%) atypical ductal hyperplasias, two (11.8%) atypical lobular hyperplasias, one (5.9%) flat epithelial atypia, and six (35.3%) papillomas. Two cases of atypical ductal hyperplasia were upgraded to DCIS at surgery. The overall cancer detection rate for gamma imaging-guided biopsy was 16.3%. In this study, gamma imaging-guided biopsy had a positive predictive value of total successful biopsies of 16.3% for cancer and 30.8% for cancer and high-risk lesions.

Conclusion: Gamma imaging-guided biopsy is a viable approach to sampling BSGI-MBI-detected lesions without sonographic or mammographic correlate. Our results compare favorably to those reported for MRI-guided biopsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.17.18513DOI Listing
March 2018

Molecular Breast Imaging: A Comprehensive Review.

Semin Ultrasound CT MR 2018 Feb 20;39(1):60-69. Epub 2017 Oct 20.

George Washington University, Comprehensive Breast Care Center, Washington, DC.

Molecular breast imaging (MBI), also called breast-specific gamma imaging (BSGI), has been an integral component of our breast imaging practice for over a decade. Unlike mammography and ultrasound that are based on anatomy, MBI is a physiologic approach to breast cancer detection. MBI detects additional foci of occult breast cancer in 9.0% of women with newly diagnosed breast cancer, has a high sensitivity for detecting high-risk lesions, and detects 98% of invasive breast cancer and 91.0% of ductal carcinoma in situ. Furthermore, in surveillance of high-risk women, BSGI/MBI detects occult cancer in up to 16.5 per 1000 women. This modality is increasingly being used to assess response to treatment in women undergoing neo-adjuvant chemotherapy and for adjunct screening in women with dense breasts. It has been shown to influence surgical management in nearly a quarter of women with newly diagnosed breast cancer. The Society of Nuclear Imaging has established clinical indications and The American College of Radiology has established appropriateness criteria as well as an accreditation program for MBI. A BIRADS-like lexicon for MBI has also been described. Initially, MBI utilized 10-20mCi of 99mTc sestamibi, however, recent studies have reported the use of 5-10mCi with equal sensitivity to the higher dose of radiotracer. There are over 300 studies in the literature about MBI/BSGI with increasing integration of MBI into clinical practice. This chapter will describe the history, current literature and indications, clinical use, approach to biopsy and integration of MBI into clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.sult.2017.10.001DOI Listing
February 2018

STK38L kinase ablation promotes loss of cell viability in a subset of KRAS-dependent pancreatic cancer cell lines.

Oncotarget 2017 Oct 11;8(45):78556-78572. Epub 2017 Sep 11.

Department of Pharmacology and Experimental Therapeutics, Center for Cancer Research, Boston University Graduate School of Medicine, Boston, MA, USA.

Pancreatic ductal adenocarcinomas (PDACs) are highly aggressive malignancies, associated with poor clinical prognosis and limited therapeutic options. Oncogenic mutations are found in over 90% of PDACs, playing a central role in tumor progression. Global gene expression profiling of PDAC reveals 3-4 major molecular subtypes with distinct phenotypic traits and pharmacological vulnerabilities, including variations in oncogenic KRAS pathway dependencies. PDAC cell lines of the aberrantly differentiated endocrine exocrine (ADEX) subtype are robustly KRAS-dependent for survival. The gene is located on chromosome 12p11-12p12, a region amplified in 5-10% of primary PDACs. Within this amplicon, we identified co-amplification of with the gene in a subset of primary human PDACs and PDAC cell lines. Therefore, we determined whether PDAC cell lines are dependent on expression for proliferation and viability. encodes a serine/threonine kinase, which shares homology with Hippo pathway kinases LATS1/2. We show that expression is elevated in a subset of primary PDACs and PDAC cell lines displaying ADEX subtype characteristics, including overexpression of mutant KRAS. RNAi-mediated depletion of STK38L in a subset of ADEX subtype cell lines inhibits cellular proliferation and induces apoptosis. Concomitant with these effects, STK38L depletion causes increased expression of the LATS2 kinase and the cell cycle regulator p21. LATS2 depletion partially rescues the cytostatic and cytotoxic effects of STK38L depletion. Lastly, high mRNA expression is associated with decreased overall patient survival in PDACs. Collectively, our findings implicate STK38L as a candidate targetable vulnerability in a subset of molecularly-defined PDACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.20833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667982PMC
October 2017

A protective role of Gαq-RGS2 loop activator on streptozotocin induced diabetic complications in rats: An independent on elevated serum glucose level modulation.

Eur J Pharmacol 2018 Jan 23;818:141-147. Epub 2017 Oct 23.

Department of Pharmacology, L.M. College of Pharmacy, Ahmedabad, Gujarat, India. Electronic address:

An overactivation of Gαq dependent signaling pathway is crucial for development of metabolic and vascular abnormalities in diabetes. Therefore, our objective was to study effects of Gαq-RGS2 loop activator (1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one) on STZ induced diabetic complications in rats. Animals were divided into four groups; normal rats, diabetic rats (Streptozotocin, STZ, 60mg/kg, i.p.), Gαq-RGS2 loop activator (1mg/kg/d, i.p., 15 d, at 6 wk after citrate buffer or STZ administration, respectively) treated normal rats and diabetic rats. At the end of 8 wk, the metabolic parameters, hemodynamic parameters, in-vivo vascular reactivity and aortic anti-oxidant status were evaluated. A treatment of Gαq-RGS2 loop activator significantly decreased serum cholesterol (P < 0.001), triglyceride (P < 0.01), systolic/diastolic/mean arterial blood pressure (P < 0.001), lactate dehydrogenase (P < 0.001), cardiac selective creatinine kinase (P < 0.001), urea (P < 0.05), creatinine (P < 0.001), aortic superoxide dismutase (P < 0.05) and catalase(P < 0.05) in diabetic rats whereas increased basal (P < 0.05) and stimulated (acetylcholine (P < 0.01) and nitroglycerine (P < 0.05)) serum nitric oxide level without affecting elevated serum glucose level. The nitroglycerin stimulated NO production was significantly (P < 0.01) increased by Gαq-RGS2 loop activator administration in normal rats, too. Collectively, Gαq-RGS2 loop activator protects rats against streptozotocin induce hemodynamic and metabolic modulation without affecting elevated serum glucose level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2017.10.046DOI Listing
January 2018

Regulation of autophagy, NF-κB signaling, and cell viability by miR-124 in mutant mesenchymal-like NSCLC cells.

Sci Signal 2017 Sep 12;10(496). Epub 2017 Sep 12.

Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.

mutant non-small cell lung cancer (NSCLC) may be classified into epithelial or mesenchymal subtypes. Despite having the same "driver" mutation, mesenchymal NSCLCs are less responsive than are epithelial NSCLCs to inhibition of the RAS pathway. Identifying alternative networks that promote survival specifically in mesenchymal NSCLC may lead to more effective treatments for this subtype. Through their numerous targets in cellular signaling pathways, noncoding microRNAs (miRNAs) often function as tumor suppressors or oncogenes. In particular, some miRNAs regulate the epithelial-mesenchymal transition (EMT). We derived an EMT-related miRNA signature by profiling the abundance of miRNAs in a panel of epithelial (KE) or mesenchymal (KM) mutant NSCLC cell lines. This signature revealed a number of suppressed miRNAs in KM cell lines, including members of the miR-200 family, which can suppress tumor progression by inhibiting EMT. Reconstituting KM cells with one of these miRNAs, miR-124, disrupted autophagy and decreased cell survival by reducing the abundance of p62, which is both an adaptor for selective autophagy and a regulator of the transcription factor nuclear factor κB (NF-κB). Suppression of p62 by miR-124 correlated with reduced abundance of the autophagy activator beclin 1 (BECN1), the ubiquitin ligase TRAF6, and the NF-κB subunit RELA/p65. The abundance of miR-124 inversely correlated with the expression of and in patient NSCLC samples. These findings reveal how the loss of miR-124 promotes cell survival networks in the aggressive mesenchymal subtype of mutant NSCLC, which might lead to improved subtype-selective therapeutic strategies for patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scisignal.aam6291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657393PMC
September 2017

Keratin 18-deficiency results in steatohepatitis and liver tumors in old mice: A model of steatohepatitis-associated liver carcinogenesis.

Oncotarget 2016 11;7(45):73309-73322

Institute of Pathology, Medical University of Graz, Graz 8036, Austria.

Backround: Steatohepatitis (SH)-associated liver carcinogenesis is an increasingly important issue in clinical medicine. SH is morphologically characterized by steatosis, hepatocyte injury, ballooning, hepatocytic cytoplasmic inclusions termed Mallory-Denk bodies (MDBs), inflammation and fibrosis.

Results: 17-20-months-old Krt18-/- and Krt18+/- mice in contrast to wt mice spontaneously developed liver lesions closely resembling the morphological spectrum of human SH as well as liver tumors. The pathologic alterations were more pronounced in Krt18-/- than in Krt18+/- mice. The frequency of liver tumors with male predominance was significantly higher in Krt18-/- compared to age-matched Krt18+/- and wt mice. Krt18-deficient tumors in contrast to wt animals displayed SH features and often pleomorphic morphology. aCGH analysis of tumors revealed chromosomal aberrations in Krt18-/- liver tumors, affecting loci of oncogenes and tumor suppressor genes.

Materials And Methods: Livers of 3-, 6-, 12- and 17-20-months-old aged wild type (wt), Krt18+/- and Krt18-/- (129P2/OlaHsd background) mice were analyzed by light and immunofluorescence microscopy as well as immunohistochemistry. Liver tumors arising in aged mice were analyzed by array comparative genomic hybridization (aCGH).

Conclusions: Our findings show that K18 deficiency of hepatocytes leads to steatosis, increasing with age, and finally to SH. K18 deficiency and age promote liver tumor development in mice, frequently on the basis of chromosomal instability, resembling human HCC with stemness features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.12325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341981PMC
November 2016

MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling.

Mol Cancer Res 2016 12 21;14(12):1204-1216. Epub 2016 Sep 21.

Department of Pharmacology and Experimental Therapeutics, Center for Cancer Research, Boston University School of Medicine, Boston Massachusetts.

MEK inhibitors have limited efficacy in treating RAS-RAF-MEK pathway-dependent cancers due to feedback pathway compensation and dose-limiting toxicities. Combining MEK inhibitors with other targeted agents may enhance efficacy. Here, codependencies of MEK, TAK1, and KRAS in colon cancer were investigated. Combined inhibition of MEK and TAK1 potentiates apoptosis in KRAS-dependent cells. Pharmacologic studies and cell-cycle analyses on a large panel of colon cancer cell lines demonstrate that MEK/TAK1 inhibition induces cell death, as assessed by sub-G accumulation, in a distinct subset of cell lines. Furthermore, TAK1 inhibition causes G-M cell-cycle blockade and polyploidy in many of the cell lines. MEK plus TAK1 inhibition causes reduced G-M/polyploid cell numbers and additive cytotoxic effects in KRAS/TAK1-dependent cell lines as well as a subset of BRAF-mutant cells. Mechanistically, sensitivity to MEK/TAK1 inhibition can be conferred by KRAS and BMP receptor activation, which promote expression of NF-κB-dependent proinflammatory cytokines, driving tumor cell survival and proliferation. MEK/TAK1 inhibition causes reduced mTOR, Wnt, and NF-κB signaling in TAK1/MEK-dependent cell lines concomitant with apoptosis. A Wnt/NF-κB transcriptional signature was derived that stratifies primary tumors into three major subtypes: Wnt-high/NF-κB-low, Wnt-low/NF-κB-high and Wnt-high/NF-κB-high, designated W, N, and WN, respectively. These subtypes have distinct characteristics, including enrichment for BRAF mutations with serrated carcinoma histology in the N subtype. Both N and WN subtypes bear molecular hallmarks of MEK and TAK1 dependency seen in cell lines. Therefore, N and WN subtype signatures could be utilized to identify tumors that are most sensitive to anti-MEK/TAK1 therapeutics.

Implications: This study describes a potential therapeutic strategy for a subset of colon cancers that are dependent on oncogenic KRAS signaling pathways, which are currently difficult to block with selective agents. Mol Cancer Res; 14(12); 1204-16. ©2016 AACR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-16-0173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136310PMC
December 2016

Effect of potassium channel openers in acute and chronic models of glaucoma.

Taiwan J Ophthalmol 2016 Jul-Sep;6(3):131-135. Epub 2016 Jun 20.

Department of Pharmacy, NIMS University, Shobha Nagar, Jaipure-Delhi Highway (NH-11C), Jaipur 303121, Rajasthan, India.

Purpose: Glaucoma is characterized by increased intraocular pressure (IOP). The effect of nicorandil and pinacidil on IOP in experimentally induced acute and chronic models of glaucoma and the mechanism of action involved were studied.

Methods: New Zealand white rabbits were used for the study. After the measurement of IOP, nicorandil (1%), pinacidil (1%), and pilocarpine as standard (1%) were instilled topically into the left eye. The other eye served as control. Dextrose (5%) was used to induce acute glaucoma. IOP changes were recorded every 15 minutes until the pressure became normal. Freshly prepared α-chymotrypsin solution was introduced in the posterior chamber to induce chronic glaucoma. Rabbits with ocular hypertension were selected for the study. Similar drug solutions were used to study the effect on IOP. Glibenclamide, pilocarpine, and indomethacin (1%) were used to study the mechanism of action of both drugs. The IOPs were measured just prior to drug instillation and at suitable time intervals using a tonometer.

Results: Pretreatment with topical nicorandil and pinacidil significantly lowered the rise in IOP in the acute model. Nicorandil and pinacidil initially caused rise in IOP for 15-30 minutes in chronic glaucoma. This was followed by reduction in IOP. Pretreatment with indomethacin and pilocarpine did not modify the effect of nicorandil and pinacidil on IOP. Pretreatment with glibenclamide blocked IOP from the lowering effect of nicorandil and pinacidil.

Conclusion: The oculohypotensive effect shown by these drugs appears to be attributable to enhancement of the aqueous humor outflow. This effect is perhaps mediated through potassium channels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tjo.2016.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525614PMC
June 2016

CT versus ultrasound guidance for percutaneous drainages in the pediatric population: an institutional review meant to limit radiation.

Clin Imaging 2016 May-Jun;40(3):431-4. Epub 2015 Dec 18.

Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.

Computed tomography (CT)-guided percutaneous drainage is a minimally invasive procedure that allows for accurate diagnosis and therapy with minimal complications. The drawback is that CT guidance carries a significant amount of radiation exposure. CT-guided percutaneous drainages have been widely used in adults and have been gaining momentum within the pediatric population. Through a thorough review of our institution's (Montefiore Medical Center) CT-guided percutaneous drainages within our pediatric patients, we assessed the radiation exposure per study as well as which studies were deemed possible under ultrasound guidance as a possible alternative.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinimag.2015.12.004DOI Listing
December 2016

A psychosocial oncology program: perceptions of the telephone-triage assessment.

Support Care Cancer 2016 07 5;24(7):2937-44. Epub 2016 Feb 5.

Ingram School of Nursing, McGill University, 3506 University St., Montreal, QC, H3A 2A7, Canada.

Purpose: Cancer can be a significant source of distress for patients and family members, which led to the creation of psychosocial oncology (PSO) programs across Canada. To access the PSO program at this institution, individuals are first triaged over the telephone by a clinical nurse specialist (CNS) who also provides psychosocial support during the call. In our study, we explored the perceptions of cancer patients or family members about their psychosocial telephone-triage assessment conducted by a CNS for a PSO program.

Methods: A qualitative descriptive design was used to explore the perceptions of nine cancer patients and family members triaged by the CNS for the PSO program. Audiotaped in-person interviews were transcribed verbatim and analyzed for themes and categories using a constant comparative method.

Results: Three major themes emerged: (1) Triage as a bridge to care, referred to the structure of telephone-triage and link to psychosocial services; (2) feeling a supportive presence, referred to the CNS' actions to foster a therapeutic relationship; and (3) different paths to tailored care, referred to the individualized strategies targeted to the participant's unique needs. As most participants described trusting the CNS, these three themes were found to emerge through a lens of trust.

Conclusion: Overall, the telephone triage was able to address the concerns of many participants and provide individualized coping strategies and support. This study further demonstrates that psychosocial support can be provided during triage over the telephone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-016-3091-8DOI Listing
July 2016

Influence of malnutrition on adverse outcome in children with confirmed or probable viral encephalitis: a prospective observational study.

Biomed Res Int 2015 28;2015:407473. Epub 2015 Jan 28.

Department of Pediatrics, BRD Medical College, Gorakhpur, India.

A prospective observational study was conducted in a tertiary care teaching hospital from August 2008 to August 2009 to explore the independent predictors of adverse outcome in the patients with confirmed/probable viral encephalitis. The primary outcome variable was the incidence of adverse outcomes defined as death or severe neurological deficit such as loss of speech, motor deficits, behavioural problems, blindness, and cognitive impairment. Patients with confirmed or probable viral encephalitis were classified into two groups based on their Z-score of weight-for-age as per WHO growth charts. Group I. Patients with confirmed or probable viral encephalitis with weight-for-age (W/A) Z-scores below -2SD were classified as undernourished. Group II. Patients with confirmed or probable viral encephalitis were classified as having normal nutritional status (weight-for-age Z-score >-2SD). A total of 114 patients were classified as confirmed or probable viral encephalitis based on detailed investigations. On multivariate logistic regression, undernutrition (adjusted OR: 5.05; 95% CI: 1.92 to 13.44) and requirement of ventilation (adjusted OR: 6.75; 95% CI: 3.63 to 77.34) were independent predictors of adverse outcomes in these patients. Thus, the results from our study highlight that the association between undernutrition and adverse outcome could be extended to the patients with confirmed/probable viral encephalitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/407473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324747PMC
November 2015

Vitamin D improves corticosteroid efficacy and attenuates its side-effects in an animal model of asthma.

Can J Physiol Pharmacol 2015 Jan;93(1):53-61

a Department of Pharmacology, L.M. College of Pharmacy, Navarangpura, Ahmedabad, Gujarat 380 009, India.

The subacute use of corticosteroids has side-effects such as glucose intolerance, dyslipidemia, anxiety, and depression, which could be halted with vitamin D, which is an immunomodulatory vitamin. Thus, we aimed to study the anti-asthmatic efficacy and side-effects profile of vitamin D, the corticosteroid dexamethasone, and their combination on ovalbumin-induced airway inflammation in rats. For this, 2 different doses of vitamin D (50 IU/kg, daily for 2 weeks, or and 60000 IU/kg, bolus dose, by intraperitoneal injection (i.p.)) were administered in combination with dexamethasone (2.5 mg/kg, i.p., for 2 weeks) prior to challenge with ovalbumin. At the end of the therapy, the asthmatic parameters such as differential white blood cell counts, serum levels of immunoglobulin E, bronchoalveolar lavaged fluid, and interleukin-5, as well as serum levels of nitric oxide were significantly increased after allergen challenges in asthmatic rats as compared with the controls. Such increases were significantly attenuated by monotherapy with vitamin D and with combination therapy of vitamin D and dexamethasone, where the combination therapy was superior to the monotherapy. Dexamethasone-induced hyperglycemia, hyperlipidemia, and behavioral abnormalities in the allergic rats were attenuated with vitamin D. The daily dose was better for controlling serum levels of immunoglobulin E than the bolus dose, whereas the bolus was superior for reducing dexamethasone-induced psychotropic abnormalities. There were no significant changes in other parameters between the daily and the bolus dose. In conclusion, a daily dose of vitamin D in combination with dexamethasone is more efficacious for treating asthma in allergic rats than monotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/cjpp-2014-0323DOI Listing
January 2015