Clinical evaluation of siddha drug Saara Parpam in the treatment of Azhal Kalladaippu (Renal Calculi)

The aim of the study is to evaluate the therapeutic efficacy of the drug Saara Parpam (internal) in Azhal Kalladaippu. Before initiating the clinical study, approval was got from the Institutional Ethical committee (NIS/6-20/IEC/15-16) for conducting the clinical study. The herbal raw drugs were authenticated by Botanist NIS and the mineral raw drugs were authenticated by Research Officer Chemistry, Department of Chemistry, Siddha Council Research Institute, Arumbakkam, Chennai and the study drug was prepared by the investigator in the Gunapadam laboratory of National Institute of Siddha as per the standard operating procedure mentioned in the protocol. The biochemical (qualitative) analyses were done at the bio chemistry lab of National Institute of Siddha. Physico chemical (quantitative) analysis, phytochemical analysis of the study drug, HPTLC and in vitro lithotriptic activity of Saara Parpam were done at Nobal Research Solutions, Sathiyabama University, and Chennai. For clinical study 80 cases were screened based on inclusion and exclusion criteria at the out patient department of Department of Maruthuvam, National Institute of Siddha. Out of 80 cases 40 cases were recruited for the clinical study. Clinical diagnosis of Azhal Kalladaippu was arrived by both Siddha and modern methodologies. Required laboratory investigations were carried out before and after treatment and the concerned data were recorded in the proforma. Before initiating the study, informed consent was obtained from the patients. A day before starting the study drug treatment, purgation was given (Agathiyar kulambu 130mg with Sankankuppi juice) early morning in empty stomach to the patients correct the elevated mukkutram. The patients were treated for a period of 48 days. The study medicine selected was Saaara parpam at the dose of 260mg twice a day with adjuvant of seerga kudineer after food. Clinical assessment was done during each visit once in 8 days and the data were noted in the prescribed proforma. During the study period there was no event of any adverse reactions owing to the drug wasreported. The biochemical study of the study drug revealed the presence of chloride, Iron, ammonium, etc. The study drug revealed the presence of phytocomponents such as alkaloids, phenols, proteins. In vitro study revealed that, the study drug “Saaraparpam” has liththotriptic action; it acted well on Struvite type of stones. Statistical analysis showed significant difference between before and after treatment in the kidney stone size (p < 0.0001) and symptoms (p < 0.0001) Clinically out of 40 cases, 22 cases (55%) had clinically good improvement (symptoms completely relived) after treated with study drug, 13cases (32.5%) had moderate improvement (symptoms reduced). 5 cases (12.5%) had no improvement. All the 40 cases were taken ultra sonography, before and after the completion of the trial drug treatment. Based on the USG Abdomen reports out of 40 cases 15 cases (37.5%) showed good improvement stone completely dissolved) 16 cases (40%) showed moderate improvement (reduction in number and size) and 9cases (22.5%) cases showed poor prognosis (no change in size and number of stone)

Improved Task Graph-based Parallel Data Processing for Dynamic Resource Allocation in Cloud

AbstractIn recent years large-set parallel data processing has gained quantum as one of the predominant applications of Infrastructure-as-a-Service (IaaS) clouds. Data processing frameworks like Google's MapReduce and its open source implementation Hadoop, Microsoft's Dryad and so on are currently in use for parallel data processing in cloud-based companies. But the problem with them is that they are designed for homogeneous environments like clusters and disregard the dynamic and heterogeneous nature of a cloud. As a result, allocation and de-allocation of compute nodes at runtime is ineffective thereby increasing processing time and cost. In this paper we present our approach towards parallel data processing exploiting dynamic resource allocation in IaaS clouds. Our architecture ensures parallel data processing using Directed Acyclic task graph. To reduce the latency and to improve throughput, load balancing is introduced in the architecture. Incoming jobs are divided into tasks that are assigned to different types of virtual machines that are dynamically instantiated and terminated during job execution

Elaborating a coiledâ coilâ assembled octahedral protein cage with additional protein domains

De novo design of protein nanoâ cages has potential applications in medicine, synthetic biology, and materials science. We recently developed a modular, symmetryâ based strategy for protein assembly in which short, coiledâ coil sequences mediate the assembly of a protein building block into a cage. The geometry of the cage is specified by the combination of rotational symmetries associated with the coiledâ coil and protein building block. We have used this approach to design wellâ defined octahedral and tetrahedral cages. Here, we show that the cages can be further elaborated and functionalized by the addition of another protein domain to the free end of the coiledâ coil: in this case by fusing maltoseâ binding protein to an octahedral protein cage to produce a structure with a designed molecular weight of ~1.8 MDa. Importantly, the addition of the maltose binding protein domain dramatically improved the efficiency of assembly, resulting in ~ 60â fold greater yield of purified protein compared to the original cage design. This study shows the potential of using small, coiledâ coil motifs as offâ theâ shelf components to design MDaâ sized protein cages to which additional structural or functional elements can be added in a modular manner.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146469/1/pro3497.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146469/2/pro3497_am.pd

A prospective, open label clinical study to evaluate the safety, efficacy and tolerability of azadvir herbal steam inhaler in asymptomatic, mildly symptomatic COVID-19 patients and health care workers posted to covid wards

Background: COVID-19 patients experience cytokine storm which cause pulmonary and extra-pulmonary complications even with currently available of standard of care. Additional antiviral and immune boosters are the need of hour to treat COVID-19 and to prevent post covid complications.Methods: In this study we enrolled 40 asymptomatic to mild COVID-19 patients to receive azadvir herbal steam inhaler along with standard of care. We evaluated the benefits of azadvir herbal steam inhaler by assessing RT-PCR conversion, clinical outcomes and improvement in immune markers (LDH, CRP, D-DIMER).Results: At the end of the study the immune markers improved significantly in study patients. In mild symptomatic cases IL-6 was 23.2 pg/ml on day 0 and 21.8 pg/ml on day 14. Reduction in IL-6 in mild symptomatic patients was statistically highly significant (p=0.0056). Mean IL-6 in asymptomatic patients was 22.3 pg/ml on day 0 and 21.1 pg/ml on day 14. Reduction in IL-6 in asymptomatic patients was statistically highly significant (p=0.0035).  Mean D-dimer was showing decreasing trend from day 0 to day 14 in mild symptomatic patients. In asymptomatic patients D dimer was 0.8 µg/ml on day 0 and 0.6 µg/ml on day 14. D-dimer decreased significantly from day 0 to day 14 (p value =0.0013). Mean LDH values on day 0 in mild symptomatic patients was 319.4 U/l and 219.3 on day 14. The reduction in LDH values in mild symptomatic patients is statistically significant (p value <0.0122). In asymptomatic patients mean LDH values on day 0 was 237 U/l and 194 U/l on day 14. The reduction in LDH values in asymptomatic group was statistically significant. Mean CRP values in mild symptomatic patients on day 0 was 12.2 mg/l and 3.8 mg/l on day 14. There was significant reduction in CRP values in mild symptomatic group which was statistically significant (p value =0.0546). Mean CRP values in asymptomatic patients on day 0 was 4.9 mg/l and 2.8 mg/l on day 14. There was significant reduction in mean CRP in asymptomatic patients which was statistically significant (p value =0.0446). In the present study all 40 patients (100%) cleared the virus and became negative for RT PCR test within 6 days. None of the patients progressed to severe COVID-19 and none of the patients succumbed to the disease.Conclusions: Azadvir accelerated recovery of COVID-19 patients by RT-PCR conversion, early improvement in clinical symptoms and immune markers in this study. This study results clearly indicates that azadvir has antiviral, immune booster activity and has definitive role in the management of asymptomatic to mild COVID-19 patients along with standard of care (CTRI no. CTRI/2020/06/026181)

Symmetryâ Directed Selfâ Assembly of a Tetrahedral Protein Cage Mediated by de Novoâ Designed Coiled Coils

The organization of proteins into new hierarchical forms is an important challenge in synthetic biology. However, engineering new interactions between protein subunits is technically challenging and typically requires extensive redesign of proteinâ protein interfaces. We have developed a conceptually simple approach, based on symmetry principles, that uses short coiledâ coil domains to assemble proteins into higherâ order structures. Here, we demonstrate the assembly of a trimeric enzyme into a wellâ defined tetrahedral cage. This was achieved by genetically fusing a trimeric coiledâ coil domain to its C terminus through a flexible polyglycine linker sequence. The linker length and coiledâ coil strength were the only parameters that needed to be optimized to obtain a high yield of correctly assembled protein cages.Geometry lesson: A modular approach for assembling proteins into largeâ scale geometric structures was developed in which coiledâ coil domains acted as â twist tiesâ to facilitate assembly. The geometry of the cage was specified primarily by the rotational symmetries of the coiled coil and building block protein and was largely independent of protein structural details.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138862/1/cbic201700406_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138862/2/cbic201700406.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138862/3/cbic201700406-sup-0001-misc_information.pd

Attitude and awareness of Indian parents from Kerala state towards children’s vaccination at the COVID-19 pandemic background

Background. Vaccination coverage of children in India is not sufficient since the COVID-19 pandemic (less than 90 %). This may lead to low adherence of parents to children’s vaccination.The aim. To study parental attitudes and awareness towards children vaccination programs in India at the COVID-19 pandemic background.Methods. Two hundred and fourteen participants from Kerala state (India) took part in the descriptive cross-sectional study via survey method. The survey was prepared with Google form according the principles of anonymity.Results. Indian parents demonstrated good adherence towards children’s vaccination, 98.6 % (95% confidence interval (CI): 95.9–99.5) of them vaccinated their child, and if vaccination appointment had to be rescheduled 84.6 % (95% CI: 79.1–88.8) of  them vaccinated children after. Most of Indians (68.7  %; 95%  CI: 62.1–74.5) preferred to vaccinate children in state clinics, however, 28.5 % (95% CI: 22.8–34.8) chose private clinics. Information about diseases that vaccines can prevent, vaccine safety, and side effects 47.2 % (95% CI: 40.6–53.8) of parents got from public pediatricians, 50.9 % (95% CI: 44.2–57.5) – from private pediatricians, and 10.3 % (95% CI: 6.8–15.0) – from complementary and alternative medicine practitioners. Over 80 % of Indians were informed about vaccination through mass media (83.6%; 95% CI: 78.1–87.9). Indian parents showed low awareness about vaccination, because 63.1 % (95% CI: 56.4–69.2) of parents wanted to know more about vaccination. Moreover, before vaccination 21.5 % (95% CI: 16.5–27.4) of them were not informed by a doctor about health benefits and possible risks for their children.Conclusion. In the COVID-19 pandemic Indian parents showed good attitude towards vaccination and low awareness in vaccination questions

The immunopeptidome from a genomic perspective:Establishing the noncanonical landscape of MHC class I–associated peptides

G.B., D.B., K.W., A.P., R.F., T.R.H., S.K., and J.A.A. received support from Fundacja na rzecz Nauki Polskiej (FNP) (grant ID: MAB/3/2017). D.R.G. received support from Genome Canada & Genome BC (grant ID: 264PRO). D.J.H. received support from NuCana plc (grant ID: SMD0-ZIUN05). H.A. received support from Swedish Cancer Foundation (grant ID: 211709). H.G. received support from United Kingdom Research and Innovation (UKRI) (grant ID: EP/S02431X/1). C.P. received support from Fundação para a Ciência e a Tecnologia (FCT) through LASIGE Research Unit (grant ID: UIDB/00408/2020 and UIDP/00408/2020). A.L. F.M.Z., C.P., A.R., A.P., and J.A.A. received support from European Union’s Horizon 2020 research and innovation programme (grant ID: 101017453). C.B. received support from Agence Nationale de la Recherche (ANR) through GRAL LabEX (grant ID: ANR-10-LABX-49-01) and CBH-EUR-GS 32 (grant ID: ANR-17-EURE0003). S.N.S. received support from Cancer Research UK (CRUK) and the Chief Scientist's Office of Scotland (CSO): Experimental Cancer Medicine Centre (ECMC) (grant ID: ECMCQQR-2022/100017). A.L. received support from Chief Scientist's Office of Scotland (CSO) NRS Career Researcher Fellowship. R.O.N. received support from CRUK Cambridge Centre Thoracic Cancer Programme (grant ID: CTRQQR-2021\100012).Tumor antigens can emerge through multiple mechanisms, including translation of non-coding genomic regions. This non-canonical category of antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry to enable the discovery of non-canonical MHC-associated peptides (ncMAPs) from non-coding regions. Considering that the emergence of tumor antigens can also involve post-translational modifications, we included an open search component in our pipeline. Leveraging the wealth of mass spectrometry-based immunopeptidomics, we analyzed 26 MHC class I immunopeptidomic studies of 9 different cancer types. We validated the de novo identified ncMAPs, along with the most abundant post-translational modifications, using spectral matching and controlled their false discovery rate (FDR) to 1%. Interestingly, the non-canonical presentation appeared to be 5 times enriched for the A03 HLA supertype, with a projected population coverage of 54.85%. Here, we reveal an atlas of 8,601 ncMAPs with varying levels of cancer selectivity and suggest 17 cancer-selective ncMAPs as attractive targets according to a stringent cutoff. In summary, the combination of the open-source pipeline and the atlas of ncMAPs reported herein could facilitate the identification and screening of ncMAPs as targeting agents for T-cell therapies or vaccine development.Publisher PDFPeer reviewe

Matrix-Bound PAI-1 Supports Cell Blebbing via RhoA/ROCK1 Signaling

The microenvironment of a tumor can influence both the morphology and the behavior of cancer cells which, in turn, can rapidly adapt to environmental changes. Increasing evidence points to the involvement of amoeboid cell migration and thus of cell blebbing in the metastatic process; however, the cues that promote amoeboid cell behavior in physiological and pathological conditions have not yet been clearly identified. Plasminogen Activator Inhibitor type-1 (PAI-1) is found in high amount in the microenvironment of aggressive tumors and is considered as an independent marker of bad prognosis. Here we show by immunoblotting, activity assay and immunofluorescence that, in SW620 human colorectal cancer cells, matrix-associated PAI-1 plays a role in the cell behavior needed for amoeboid migration by maintaining cell blebbing, localizing PDK1 and ROCK1 at the cell membrane and maintaining the RhoA/ROCK1/MLC-P pathway activation. The results obtained by modeling PAI-1 deposition around tumors indicate that matrix-bound PAI-1 is heterogeneously distributed at the tumor periphery and that, at certain spots, the elevated concentrations of matrix-bound PAI-1 needed for cancer cells to undergo the mesenchymal-amoeboid transition can be observed. Matrix-bound PAI-1, as a matricellular protein, could thus represent one of the physiopathological requirements to support metastatic formation