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Sidhhamantra Nighantu is one such unique lexicon which has a chapter named as Tridoshaghna Varga which enlists the drugs which pacify one, two or all the three Doshas i.e., Vata, Pitta and Kapha. Drugs pacifying all the three Doshas are unique in their Rasa Panchaka in terms of specific combination of Rasa, Guna, Virya and Vipaka. The Tridoshaghna concept and this chapter both stand unique and hence the present chapter was selected for its exploration through multiple correspondence analysis. Materials and Methods: All the relevant information about the drugs like their Botanical identity, family, Rasa, Guna, Virya and Vipaka of Tridoshaghna varga was collected with the help of previous and successive texts of Sidhhamantra Nighantu. The collected information was subjected to multiple correspondence analysis. Result: The chapter Tridoshaghna Varga enlists several substances of herbal origin, metallic/mineral origin and animal origin. MCA revealed that the combination of Sheeta Virya and Madhura Vipaka with the combination of Tikta and/or Katu Rasa can be the best properties for Tridoshaghna action in majority diseased conditions. Conclusion: The study data should be considered while clinical practice by clinicians and further studies should be carried out on the nutritional foods included in the chapter for better understanding of Aahara (nutritional herbs) as well as Aushadha (medicinal herbs) for Tridoshaghna action.

Introduction: Different types of Snehapaka have been mentioned in Sarangdhar Samhita such as Mrudu Paka, Madhyama Paka, Khara Paka, Dagdha Paka, Ama Paka, and Gandha Paka. Further, different uses of sneha according to its paka had been mentioned in which Madhyama Paka and Khara Paka are stated to be used for internal (Pana) and external (Abhyang), respectively. Aim: The present study was carried out to discriminate type of paka in Katupila taila on the basis of classical and modern parameters, namely, Paka pariksha, organoleptic-physicochemical parameters, and chromatography. Results: Average 934.8 g (93.48% yield) and 845.33 g (84.53% yield) of Katupila Taila madhyama paka (KPTM) and Khara paka, respectively, was obtained from batch size of, 1 L of Tila Taila with 212 g of Kalka dravya and 4 L of Kwatha of Katupila stem. Temperature reached up to 92°C and 97°C, respectively, for completion of Madhyama Paka and Khara Paka. Heating was carried out for 3 consecutive days for both Paka. Discussion: Average duration between initiation of Madhyama Paka and end of Khara Paka was 1 h and 44 min. Here, temperature and duration of heating play a major role in the type of Paka. It showed difference in the values of physicochemical parameters of both Paka. KPTM and Khara paka were having specific gravity (0.9179 ± 0.0050 and 0.9294 ± 0.0067), refractive index (1.449 ± 0.009 and 1.474 ± 0.015), acid value (2.908 ± 0.0538 and 1.809 ± 0.0472), iodine value (108.075 ± 2.9793 and 72.875 ± 3.2548), saponification value (169.66 ± 8.9132 and 226.64 ± 6.1567), and BTTT value (19.6 ± 0.3, 28.5 ± 0.5), respectively.

Supplementary Table 1 from Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

Supplementary Figure Legends 1-4 from Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

Supplementary Figure 1 from Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

Supplementary Figure 2 from Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

Daunorubicin is an anthracycline antibiotic agent used in the treatment of hematopoietic malignancies. Toxicities associated with this agent include myelosuppression and cardiotoxicity; however, the genes or genetic determinants that contribute to these toxicities are unknown. We present an unbiased genome-wide approach that incorporates heritability, whole-genome linkage analysis, and linkage-directed association to uncover genetic variants contributing to the sensitivity to daunorubicin-induced cytotoxicity. Cell growth inhibition in 324 Centre d' Etude du Polymorphisme Humain lymphoblastoid cell lines (24 pedigrees) was evaluated following treatment with daunorubicin for 72 h. Heritability analysis showed a significant genetic component contributing to the cytotoxic phenotypes (h2 = 0.18–0.63 at 0.0125, 0.025, 0.05, 0.1, 0.2, and 1.0 μmol/L daunorubicin and at the IC50, the dose required to inhibit 50% cell growth). Whole-genome linkage scans at all drug concentrations and IC50 uncovered 11 regions with moderate peak LOD scores (>1.5), including 4q28.2 to 4q32.3 with a maximum LOD score of 3.18. The quantitative transmission disequilibrium tests were done using 31,312 high-frequency single-nucleotide polymorphisms (SNP) located in the 1 LOD confidence interval of these 11 regions. Thirty genes were identified as significantly associated with daunorubicin-induced cytotoxicity (P ≤ 2.0 × 10−4, false discovery rate ≤ 0.1). Pathway and functional gene ontology analysis showed that these genes were overrepresented in the phosphatidylinositol signaling system, axon guidance pathway, and GPI-anchored proteins family. Our findings suggest that a proportion of susceptibility to daunorubicin-induced cytotoxicity may be controlled by genetic determinants and that analysis using linkage-directed association studies with dense SNP markers can be used to identify the genetic variants contributing to cytotoxicity. [Cancer Res 2007;67(11):5425–33]

Supplementary Figure 3 from Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

Supplementary Figure 4 from Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT −/− mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor β1 ( TGF β 1 ) and collagen ( COL1A1 ) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

Background The THUNDERBEAT is a multi-functional energy device which delivers both ultrasonic and bipolar energy, but there are no randomized trials which can provide more rigorous evaluation of the clinical performance of THUNDERBEAT compared to other energy-based devices in colorectal surgery. The aim of this study was to compare the clinical performance of THUNDERBEAT energy device to Maryland LigaSure in patients undergoing left laparoscopic colectomy. Methods Prospective randomized trial with two groups: Group 1 THUNDERBEAT and Group 2 LigaSure in a single university hospital. 60 Subjects, male and female, of age 18 years and above undergoing left colectomy for cancer or diverticulitis were included. The primary outcome was dissection time to specimen removal (DTSR) measured in minutes from the start of colon mobilization to specimen removal from the abdominal cavity. Versatility (composite of five variables) was measured by a score system from 1 to 5 (1 being worst and 5 the best), and adjusted/weighted by coefficient of importance with distribution of the importance as follow: hemostasis 0.275, sealing 0.275, cutting 0.2, dissection 0.15, and tissue manipulation 0.1. Other variables were: dryness of surgical field, intraoperative and postoperative complications, and mortality. Follow-up time was 30 days. Results 60 Patients completed surgery, 31 in Group 1 and 29 in Group 2. There was no difference in the DTSR between the groups, 91 min vs. 77 min (p = 0.214). THUNDERBEAT showed significantly higher score in dissecting and tissue manipulation in segment 3 (omental dissection), and in overall versatility score (p = 0.007) as well as versatility score in Segment 2 (retroperitoneal dissection p = 0.040) and Segment 3 (p = 0.040). No other differences were noted between the groups. Conclusions Both energy devices can be employed effectively and safely in dividing soft tissue and sealing mesenteric blood vessels during laparoscopic left colon surgery, with THUNDERBEAT demonstrating some advantages over LigaSure during omental dissection and tissue manipulation. ClinicalTrial.gov # NCT02628093.

Cytokeratin and desmin expression have been associated with Sertoli cell maturity and the development of testicular germ cell cancer (TGCC). Thus, the present study aimed to characterize the expression of these intermediate filaments in normal testis development and TGCC. Cytokeratin and desmin were determined by immunohistochemistry and immunofluorescence in human fetal, and adult testis and tissue from patients with pre-invasive germ cell neoplasia in-situ (GCNIS) or invasive TGCC. Desmin was expressed in Sertoli cells of the human fetal testis, and the proportion of desmin expressing Sertoli cells was significantly reduced in the second trimester, compared with the first trimester (31.14% vs. 6.74%, p = 0.0016). Additionally, Desmin was expressed in the majority of Sertoli cells in the adult testis and TGCC samples. Cytokeratin was detected in Sertoli cells of human fetal testis but was not expressed in Sertoli cells of human adult testis. In patients with TGCC, cytokeratin was not expressed in Sertoli cells in tubules with active spermatogenesis but was detected in Sertoli cells in tubules containing GCNIS cells in patients with both pre-invasive and invasive TGCC. In conclusion, desmin was not associated with Sertoli cell maturation or progression to TGCC. However, cytokeratin appeared to be an indicator of impaired Sertoli cell maturation.

Sensory evaluation is a quantitative science in which numerical data are collected to establish lawful and specific relationships between product characteristics and human perception. Among the sensory methods available, Triangle test method was adopted. The purpose of this study was to differentiate Madhyama Paka and Khara Paka Katupila Taila with regard to smell and color. Forty pre-trained assessors were asked to identify the blindly coded sample analogous. The results were calculated using Python software and analyzed using receiver operating characteristics curve, area under curve (AUC), and d-prime (d’) with the help of sensR package in R-studio ver. 1.0.143. For both attributes, both the samples were correctly identified with a significance level of P < 0.001 and AUC of 1 and 0.999 for each set, respectively. Thus, it can be concluded that sensory analysis method efficiently discriminated the Madhyama Paka and Khara Paka Katupila Taila samples and thus can serve as a cost-effective routine quality control tool.

The accumulation of neurofibrillary tangles (NFTs), which is composed of abnormally hyperphosphorylated tau aggregates, is the classic neuropathology associated with cognitive dysfunction in tauopathies such as Alzheimer’s disease (AD). However, there is an emerging theory suggesting that dysregulation in cerebral iron may contribute to NFT formation. Iron is speculated to bind to tau and induce conformational changes of the protein, potentially leading to subsequent aggregation and cognitive decline. Deferiprone (DFP) is a clinically available iron chelator, which has demonstrated potential therapeutic advantages of chelating iron in neurodegenerative disorders, and is currently in clinical trials for AD. However, its effect on tau pathology remains unclear. Here, we report the effects of short-term DFP treatment (4 weeks, 100 mg/kg/daily, via oral gavage) in a mixed-gender cohort of the rTg((tauP301L))4510 mouse model of tauopathy. Our results revealed that DFP improved Y-maze and open field performance, accompanied by a 28% decrease in brain iron levels, measured by inductively coupled plasma mass spectrometry (ICP-MS) and reduced AT8-labeled p-tau within the hippocampus in transgenic tau mice. This data supports the notion that iron may play a neurotoxic role in tauopathies and may be a potential therapeutic target for this class of disorders that can be modulated by the clinically available metal chelator DFP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-020-00972-w.

To evaluate patterns of use and outcomes of arteriovenous fistulas and prosthetic grafts within racial categories in a large population based cohort of hemodialysis (HD) patients in the United States.A retrospective analysis of white, black, and Hispanic patients in the prospectively maintained United States Renal Database System who had an autogenous fistula or prosthetic graft placed for HD access between January 2007 and December 2014 was performed. Analysis of variance, χThis study of 359,942 patients, composed of 285,781 autogenous fistulas (79.4%) and 74,161 prosthetic grafts (20.6%) placed in 213,877 white (59.4%), 115,727 black (32.2%), and 30,338 Hispanic (8.4%) patients. There was a 11% increase in the risk-adjusted odds of HD catheter use as bridge to autogenous fistula placement in blacks (adjusted odds ratio, 1.11; 95% confidence interval [CI], 1.08-1.14; P .001) and a 9% increase in Hispanics (adjusted odds ratio, 1.09; 95% CI, 1.05-1.14; P .001) compared with whites. Fistula maturation for HD access for whites vs blacks vs Hispanics was 77.0% vs 76.3% vs 77.8% (P = .35). After adjusting for covariates, fistula maturation was higher for blacks (adjusted hazard ratio, 1.09; 95% CI, 1.06-1.13; P .001) and Hispanics (adjusted hazard ratio, 1.13; 95% CI, 1.06-1.20; P .001) compared with whites. There was no significant difference in prosthetic graft maturation for blacks and Hispanics compared with whites. Primary, primary-assisted, and secondary patency were highest for Hispanic and least for black autogenous fistula recipients. Primary, primary-assisted, and secondary patency was also highest for Hispanic patients who received prosthetic grafts. Prosthetic grafts were associated with a decrease in patency and patient survival compared with fistulas in all racial categories. Mortality was lower for blacks and Hispanics relative to white patients. Initiation of HD with a catheter and conversion to autogenous fistula was associated with decrease in patency and patient survival compared with initiation with a fistula in all racial groups.Autogenous fistulas are associated with better patency and patient survival compared with prosthetic grafts for all races studied. The use of HD catheter before fistula placement is more prevalent in Hispanic and black patients and is associated with worse patency and patient survival irrespective of race. Fistula and graft patency is highest for Hispanic patients. Patient survival is higher for Hispanic and black patients relative to whites. These associations suggest potential benefit with initiation of HD via autogenous fistula and minimizing temporizing catheter use, irrespective of race.

Background: An elevation in iron levels, together with an accumulation of α-synuclein within the oligodendrocytes, are features of the rare atypical parkinsonian disorder, Multiple System Atrophy (MSA). We have previously tested the novel compound ATH434 (formally called PBT434) in preclinical models of Parkinson’s disease and shown that it is brain-penetrant, reduces iron accumulation and iron-mediated redox activity, provides neuroprotection, inhibits alpha synuclein aggregation and lowers the tissue levels of alpha synuclein. The compound was also well-tolerated in a first-in-human oral dosing study in healthy and older volunteers with a favorable, dose-dependent pharmacokinetic profile. Objective: To evaluate the efficacy of ATH434 in a mouse MSA model. Methods: The PLP-α-syn transgenic mouse overexpresses α-synuclein, demonstrates oligodendroglial pathology, and manifests motor and non-motor aspects of MSA. Animals were provided ATH434 (3, 10, or 30 mg/kg/day spiked into their food) or control food for 4 months starting at 12 months of age and were culled at 16 months. Western blot was used to assess oligomeric and urea soluble α-synuclein levels in brain homogenates, whilst stereology was used to quantitate the number of nigral neurons and glial cell inclusions (GCIs) present in the substantia nigra pars compacta. Results: ATH434 reduced oligomeric and urea soluble α-synuclein aggregation, reduced the number of GCIs, and preserved SNpc neurons. In vitro experiments suggest that ATH434 prevents the formation of toxic oligomeric “species of synuclein”. Conclusion: ATH434 is a promising small molecule drug candidate that has potential to move forward to trial for treating MSA.

Previous studies have examined the relationship between colorectal tumor distribution and metastasis, but the tumor luminal location and associative risk factors promoting tumor growth remain unknown.In this study, we mapped the luminal distribution of human colonic adenomas/adenocarcinomas and their association with various physiologic parameters.We identified a mesenteric predominance for colonic adenomas and adenocarcinomas.The findings of this study raise the possibility of novel mechanistic pathways in the development of adenomas and subsequent transformation into adenocarcinomas.

Direct-injection spark-ignition engines can be more sensitive to fuel type as the time available for spray formation and mixing is rather limited. The challenge is further complicated by fuel stock which includes a significant bio-derived component in some markets to manage fuel sustainability. The thermophysical properties of bio-components like ethanol differ markedly from typical hydrocarbons found in gasoline like iso-octane. Moreover, the production of anhydrous ethanol fuel involves separating water and ethanol by distillation and dehydration in an energy intensive process. This study presents results from an optical investigation into the spray formation process of hydrous ethanol fuels with 4–15% water content per volume in direct comparison to anhydrous ethanol and iso-octane. Injection tests were carried out with 20–110°C fuel temperature at 1.0 bar and 0.5 bar gas pressure to mimic thermodynamic conditions of cold-start and fully-warm engine at low-load and wide-open-throttle operation. High-speed spray imaging was conducted along with droplet sizing by phase Doppler anemometry. The thermophysical properties of all fuels, including vapour pressure, density, viscosity and surface tension, as well as distillation curves, were obtained over a range of temperatures and the respective Reynolds, Weber and Ohnesorge numbers were considered in the analysis. At 20°C iso-octane and anhydrous ethanol exhibited similar spray plume penetration, whilst increasing water content in ethanol reduced spray penetration. At higher temperatures up to 90°C, anhydrous ethanol showed lower penetration than iso-octane whilst the hydrous fuels still exhibited lower penetration than anhydrous ethanol in sequence of increasing water content. At 110°C, the ethanol fuels showed signs of plume merging and spray collapse, particularly at 0.5 bar gas pressure, with clear differences from iso-octane. The degree of plume merging and collapse was stronger with increased water content. The cone angle for the hydrous fuels was higher than that of pure ethanol, with the 4% water content ethanol that was close to the azeotropic point showing wider cone angle at temperatures higher than 20°C, being distinctly higher at 90°C. Iso-octane had consistently smaller droplet Sauter mean diameter than the ethanol fuels. As the percentage of water content in ethanol increased there was an increase in droplet sizes at all conditions.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

Background Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4−), which fail to differentiate to pre-spermatogonia (POU5F1−/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC. Methods We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9–20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma). Results Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cells and NTera2 cells. Gankyrin knock-down in NTera2 cells resulted in an increase in apoptosis mediated via the TP53 pathway, whilst POU5F1 expression was unaffected. Furthermore, Gankyrin knock-down in NTera2 cells increased cisplatin sensitivity with an increase in cell death (13%, p Conclusions These results suggest that manipulation of Gankyrin expression may reduce the cisplatin dose required for the treatment of TGCC, with benefits in reducing dose-dependent side effects of chemotherapy. Further studies are required in order to assess the effects of modulating Gankyrin on GCNIS/TGCC using in vivo models.

OBJECTIVE To estimate the cost of delivering a hepatitis C virus care coordination program at 2 New York City health care provider organizations and describe a potential payment model for these currently nonreimbursed services. DESIGN An economic evaluation of a hepatitis C care coordination program was conducted using micro-costing methods compared with macro-costing methods. A potential payment model was calculated for 3 phases: enrollment to treatment initiation, treatment initiation to treatment completion, and a bonus payment for laboratory evidence of successful treatment outcome (sustained viral response). SETTING Two New York City health care provider organizations. PARTICIPANTS Care coordinators and peer educators delivering care coordination services were interviewed about time spent on service provision. De-identified individual-level data on study participant utilization of services were also used. INTERVENTION Project INSPIRE is an innovative hepatitis C care coordination program developed by the New York City Department of Health and Mental Hygiene. MAIN OUTCOME MEASURES Average cost per participant per episode of care for 2 provider organizations and a proposed payment model. RESULTS The average cost per participant at 1 provider organization was $787 ($522 nonoverhead cost, $264 overhead) per episode of care (5.6 months) and $656 ($429 nonoverhead cost, $227 overhead, 5.7 months) at the other one. The first organization had a lower macro-costing estimate ($561 vs $787) whereas the other one had a higher macro-costing estimate ($775 vs $656). In the 3-phased payment model, phase 1 reimbursement would vary between the provider organizations from approximately $280 to $400, but reimbursement for both organizations would be approximately $220 for phase 2 and approximately $185 for phase 3. CONCLUSIONS The cost of this 5.6-month care coordination intervention was less than $800 including overhead or less than $95 per month. A 3-phase payment model is proposed and requires further evaluation for implementation feasibility. Project INSPIRE's HCV care coordination program provides good value for a cost of less than $95 per participant per month. The payment model provides an incentive for successful cure of hepatitis C with a bonus payment; using the bonus payment to support HCV tele-mentoring expands HCV treatment capacity and empowers more primary care providers to treat their own patients with HCV.

Thalassemia is one of the most challenging form of Haematological disorders. Gandhakadi Yoga is an Ayurvedic medicine comprising of SHUDDHA GANDHAKA (Sulphur), VIDANGA (Embelia ribes Burm.f.), AGASTYA PATRA (Sesbaniya grandifoliya Linn.), SHIGRU PATRA (Moringa Oleifera Lam.). Gandhakadi Yoga is a customized preparation of the formulation proposed for Loha Sevanajanya Vikara Prashamana (iron overloading) in Ayurveda Prakasha. here in Gandhaka and Vidanga are triturated with Agatsya patra Swarasa and then used therapeutically. So in the present study the formulation Gandhakadi Yoga has been selected for clinical evaluation on patients of Thalassemia Major, against the standard conventional approach (i.e. Blood Transfusion & Iron chelation therapy). The Pharmacognostical features of Gandhakadi Yoga Vati under the microscope observed that Oil globules, stone cell and Epicarp cells of Vidanga (Embelia ribesBur m.f.), Fragmented Unicellular Cell of Shigru, Simple Fiber of Shigru, Simple Trichome of Bhringraja base of Bhringaraja (E.alba.) and Crystaline depositions of Gandhaka were microscopically. Organoleptic features of finished product were within the normal range described in the classic.

Multiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using chelators could slow down the disease progression. In human MSA, there is evidence of increased iron in affected brain regions, but role of iron and therapeutic efficacy of iron-lowering drugs in pre-clinical models of MSA have not been studied. We studied age-related changes in iron metabolism in different brain regions of the PLP-αsyn mice and tested whether iron-lowering drugs could alleviate disease phenotype in aged PLP-αsyn mice. Iron content, iron-ferritin association, ferritin protein levels and copper-ceruloplasmin association were measured in prefrontal cortex, putamen, substantia nigra and cerebellum of 3, 8, and 20-month-old PLP-αsyn and age-matched non-transgenic mice. Moreover, 12-month-old PLP-αsyn mice were administered deferiprone or ceruloplasmin or vehicle for 2 months. At the end of treatment period, motor testing and stereological analyses were performed. We found iron accumulation and perturbed iron-ferritin interaction in substantia nigra, putamen and cerebellum of aged PLP-αsyn mice. Furthermore, we found significant reduction in ceruloplasmin-bound copper in substantia nigra and cerebellum of the PLP-αsyn mice. Both deferiprone and ceruloplasmin prevented decline in motor performance in aged PLP-αsyn mice and were associated with higher neuronal survival and reduced density of α-synuclein aggregates in substantia nigra. This is the first study to report brain iron accumulation in a mouse model of MSA. Our results indicate that elevated iron in MSA mice may result from ceruloplasmin dysfunction and provide evidence that targeting iron in MSA could be a viable therapeutic option.

Due to the immediate need for social distancing, as well as widespread disruption in clinical practices, brought on by the novel severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic, medical student education rapidly shifted to a virtual format, which resulted in a variety of innovative and remotely accessible practices to address new restrictions on face-to-face education. Educators approached curriculum design seeking to replicate as much of the in-person experience as possible, and were faced with overcoming the challenges of replacing the innately hands-on nature of surgery with virtual operative and skills experiences. Restrictions on in-person visiting electives expedited the role of virtual education as a notable opportunity for medical student education and recruitment, with a variety of approaches to engaging undergraduate medical learners, including the use of live-streaming operative cases, virtual didactic curricula, and a rise in podcasts; web-based conferences; and virtual journal clubs. In addition to education, virtual outreach to medical students has become an essential tool in trainee recruitment and selection, and ongoing application of novel educational platforms will allow for new opportunities in multi-institutional collaboration and exchange with a multitude of benefits to future vascular surgery trainees. Our aim was to outline the resources and practices used to virtually teach and recruit medical students and the benefits of virtual rotations to the program and students.

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30, 860 articles reviewed, 328 randomized controlled trials on 35, 600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and

OBJECTIVE: While up to 35% of children with asthma have evidence of sleep disordered breathing (SDB), it is unclear if nocturnal symptoms stem from asthma itself or SDB. The Pediatric Sleep Questionnaire (PSQ) is a validated tool for identifying SDB in childhood asthma. We hypothesize children with asthma and abnormal PSQ demonstrate decreased asthma control and are at higher risk of obstructive sleep apnea (OSA). METHODS: We performed a retrospective, chart review of children and young adults referred to our tertiary children’s hospital severe asthma clinic. Data collection included age, gender, BMI percentile, spirometry, PSQ, asthma control questionnaires, asthma severity, control, and impairment. These data were evaluated in the context of polysomnography, when available. RESULTS: 205 inner-city children were included; 37.2% female, median age 6.4y, and mean BMI of 71.3%ile. Rhinitis (p=0.028), eczema (p=0.002), and reflux (p=0.046) were associated with abnormal PSQ; however, overweight/obese status, spirometry, asthma severity, and serologic markers were not. After correcting for comorbidities, abnormal PSQ score was associated with poor asthma control based on validated measures (p

Alang, ship breaking yard situated on north-west edge of Gulf of Khambhat. It is famous for ship breaking yard and contains very harmful heavy metals. Lead contamination is highest in Alang. To decrease the concentration of heavy metals many different physical, chemical and biological methods are available but they are harmful to nature and waste more quantity of chemicals. So, bioremediation is the best method to remove pollutants. A low concentration of heavy metals is required to plant for their growth and metabolic process but at higher concentration, plants do not survive. With the use of microbes, we can survive plants at certain levels. During this work, heavy metal tolerating microorganism was isolated from sea water of Alang and purified. Various tests were performed for identification and primary screening. in vitro examination in the different plants like moong, wheat, peanut, kidney beans and mat beans under 500ppm Pb concentration.