721 research outputs found

    GM1 Ganglioside Modifies α-Synuclein Toxicity and is Neuroprotective in a Rat α-Synuclein Model of Parkinson\u27s Disease.

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    While GM1 may interact with α-synuclein in vitro to inhibit aggregation, the ability of GM1 to protect against α-synuclein toxicity in vivo has not been investigated. We used targeted adeno-associated viral vector (AAV) overexpression of human mutant α-synuclein (A53T) in the rat substantia nigra (SN) to produce degeneration of SN dopamine neurons, loss of striatal dopamine levels, and behavioral impairment. Some animals received daily GM1 ganglioside administration for 6 weeks, beginning 24 hours after AAV-A53T administration or delayed start GM1 administration for 5 weeks beginning 3 weeks after AAV-A53T administration. Both types of GM1 administration protected against loss of SN dopamine neurons and striatal dopamine levels, reduced α-synuclein aggregation, and delayed start administration of GM1 reversed early appearing behavioral deficits. These results extend prior positive results in MPTP models, are consistent with the results of a small clinical study of GM1 in PD patients that showed slowing of symptom progression with chronic use, and argue for the continued refinement and development of GM1 as a potential disease modifying therapy for PD

    Wavelet-based medical image fusion via a non-linear operator

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    Medical image fusion has been extensively used to aid medical diagnosis by combining images of various modalities such as Computed Tomography (CT) and Magnetic Resonance Image (MRI) into a single output image that contains salient features from both inputs. This paper proposes a novel fusion algorithm through the use of a non-linear fusion operator, based on the low sub-band coefficients of the Discrete Wavelet Transform (DWT). Rather than employing the conventional mean rule for approximation sub-bands, a modified approach is taken by the introduction of a non-linear fusion rule that exploits the multimodal nature of the image inputs by prioritizing the stronger coefficients. Performance evaluation of CT-MRI image fusion datasets based on a range of wavelet filter banks shows that the algorithm boasts improved scores of up to 92% as compared to established methods. Overall, the non-linear fusion rule holds strong potential to help improve image fusion applications in medicine and indeed other fields

    A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

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    BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

    Duplex Moiety Kidney With Ureteral Ectopia; A Case Series

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    Ureteral ectopia is a common condition presenting as incontinence in females and incidentally detected in males. The diagnosis requires thorough radiological investigations to delineate the anatomy and formulate the treatment. The prognosis is generally excellent. We presented a series of three cases of ureteral ectopia and discussion regarding their management.Keywords: Female; Urinary Incontinence; Ectopic Ureter; Duplex Moiety Kidney

    A Novel approach for Agrobacterium-mediated germ line transformation of Indian Bread wheat (Triticum aestivum) and Pasta wheat (Triticum durum)

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    Recalcitrance of wheat towards tissue culture procedures has hampered the wide use of conventional transformation techniques for its improvement. In the present study, a novel, non-tissue culture, cost effective approach has been established for the introduction of transgenes in wheat. Dry, mature seeds of two Indian varieties of wheat, Triticum aestivum cv. HD2329 (bread wheat), and Triticum durum cv. PDW215 (pasta wheat), were co-cultivated with Agrobacterium strain GV2260 (p35SGUSINT) and LBA4404 (pCAMBIA 3301), respectively, in the presence of 200 μM acetosyringone. The plantlets testing gus positive were raised till maturity in garden pots. T0 lines were screened by PCR for presence of selectable markers in the transformed plants followed by confirmation with Southern hybridization. In bread wheat, nptII was detected in five primary transformed lines (T0) (ws1, ws2, ws3, ws4, ws5) and the bar gene in three putatively transformed durum wheat lines (wsb1, wsb2, wsb3). The transformation efficiency was calculated as 1.16%, and 0.84% for T. aestivum and T. durum, respectively.Â

    AFLP MARKERS BASED DIVERSITY ANALYSIS AMONG WILD RELATIVES OF TOMATO COLLECTED FROM CHHATTISGARH REGIONS OF INDIA

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    The cultivated Tomato (Solanum lycopersicum) is the second most consumed vegetable worldwide and a well studied crop species in terms of genetics, genomics, and breeding. For the current study wild relatives consisted of cherry and medium sized tomato fruits of 10 tomato genotypes were collected from different regions of Chhattisgarh in order to find out the genetic diversity among these. AFLP analysis revealed that, a total of 2209 reliable polymorphic bands were observed in the 9 AFLP gels varied from 128 to 417, of which only 3 was monomorphic across all 10 genotype. The average no of polymorphic bands present across genotype per primer combination varied from 2.11- 5.48. All the primer combination used in this study has >0.800 PIC value and ranged from 0.813 (ESA14 Vs MSA12) to 0.898 (ESA13 Vs MSA14). The Jaccard’s similarity coefficient for AFLP data set varied from 0.13 to 0.60. The 10 genotype formed 2 major clusters at 13 % similarity level. The lowest similarity (0.13) was between genotypes Raipur cherry and Janjgir long which were the most divergent while the highest similarity (0.72) was found between the genotypes jashpur cherry and Janjgir cripping. This study demonstrated that AFLP markers are effective for obtaining unique fingerprints of, and assessing genetic diversity among, tomato wild relatives

    Drug repurposing in the treatment of COVID-19: A review

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    The first outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was in Wuhan, Hubei, China in December 2019 and declared as a pandemic by the World Health Organization. Currently, there is no proven effective vaccine or therapeutic agent to combat the deadly coronavirus disease. Currently, prevention from the infection, control measures and supportive care help to treat against COVID-19. Until an effective vaccine is available for COVID-19 infection, one can repurpose known therapeutic agents that block the entry of the virus into the host cell and control the COVID-19 infection. Drug repurposing is the new use of old drugs. In this review, the most common and possible drug treatment for COVID-19 is highlighted. The therapeutic agents include antiviral drugs like Remdesivir, chloroquine, hydroxychloroquine, lopinavir/ritonavir, umifenovir, favipiravir and oseltamivir and other agents. Clinical trials are ongoing to evaluate the safety and efficacy of these therapeutic agents in COVID-19 patients
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