A Framework for Estimating Mold Performance Using Experimental and Numerical Analysis of Injection Mold Tooling Prototypes

Additive Manufacturing (AM), 3D printing, rapid prototyping, or rapid tooling refer to a range of technologies that are capable of translating virtual CAD model data into physical model. It is executed in growing number of applications nowadays. A wide range of materials are currently being used to produce consumer products and production tools. AM has brought in revolutionary changes in traditional manufacturing practices. Yet, there are certain drawbacks that hinder its advancement at mass manufacturing. High cost associated with AM is one of them. Using 3D printed tooling can provide long-time cost effectiveness and better product quality. Additively manufactured injection molds can increase the cooling performance, reduce production cycle time, and improve surface finish and part quality of the final plastic product. Yet, manufacturers are still not using the printed molds for industrial mass production. Numerical analysis can provide approximation of such improved performance, but, factual experimental results are necessary to satisfy performance criteria of molds to justify the large investment into tooling for existing industries. In this research work, a desktop injection molding machine is used to evaluate performance of 3D printed molds to develop a cost and performance analysis tool. It serves as a baseline to predict the performance of molds in real-time mass manufacturing of consumer products. The analysis describes how appropriate the estimation can be from any simulation study of molds, how much the scaling down of tool and molding system can affect the prediction of actual performance, what correction factors can be used for better approximation of performance matrices. Several “scaled down” prototypes of injection molds have been used. They have design variations as: with or without cooling system, conformal or straight cooling channels, solid or lattice matrix, and metal or tough resin as the mold material. The molds are printed in in-house printing machines and can also be printed online with limited charges. This also provides an excellent demonstration of using inexpensive material and manufacturing process, such as resin to estimate the performance of highly expensive 3D printed stainless steel molds. The work encompasses a framework to reduce overall cost of implementing AM, by lowering time and monetary expenses during the research and development, and prototyping phases

Proximity to healthcare centres and service use: The case of Community Clinics in Bangladesh

CAUL read and publish agreement 2023fals

Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to Substance P, Hemokinin-1, Human B-Defensin-3, and Icatibant

Human mast cells (MCs) express a novel G protein–coupled receptor (GPCR) known as Mas-related GPCR X2 (MRGPRX2). Activation of this receptor by a diverse group of cationic ligands such as neuropeptides, host defense peptides, and Food and Drug Administration–approved drugs contributes to chronic inflammatory diseases and pseudoallergic drug reactions. For most GPCRs, the extracellular (ECL) domains and their associated transmembrane (TM) domains display the greatest structural diversity and are responsible for binding different ligands. The goal of the current study was to determine if naturally occurring missense variants within MRGPRX2’s ECL/TM domains contribute to gain or loss of function phenotype for MC degranulation in response to neuropeptides (substance P and hemokinin-1), a host defense peptide (human b-defensin-3) and a Food and Drug Administration–approved cationic drug (bradykinin B2 receptor antagonist, icatibant). We have identified eight missense variants within MRGPRX2’s ECL/TM domains from publicly available exome-sequencing databases. We investigated the ability of MRGPRX2 ligands to induce degranulation in rat basophilic leukemia–2H3 cells individually expressing these naturally occurring MRGPRX2 missense variants. Using stable and transient transfections, we found that all variants express in rat basophilic leukemia cells. However, four natural MRGPRX2 variants, G165E (rs141744602), D184H (rs372988289), W243R (rs150365137), and H259Y (rs140862085) failed to respond to any of the ligands tested. Thus, diverse MRGPRX2 ligands use common sites on the receptor to induce MC degranulation. These findings have important clinical implications for MRGPRX2 and MC-mediated pseudoallergy and chronic inflammatory diseases. Copyright © 2018 by The American Association of Immunologists, Inc

Effect of obestatin on morphometry of testes and testosterone secretion in male rats

This study was designed to evaluate the effects of chronic intra peritoneal administration of obestatin on plasma testosterone concentrations and cellular morphometry of the testes in male Sprague Dawly rats. The treatment groups were injected with obestatin (1 nmol/100 μl saline i.p), while the control groups received saline (100 μl i.p) for ten consecutive days. Blood samples were collected at day 1 and 10 during the dose administration and day 5 and 15 after the dose administration. All the samples were collected at 10:00 a.m. Testes were removed after sacrificing the rats on days 5 and 15 after the last injection. Plasma testosterone concentrations were found significantly high (p < 0.05) in the obestatin treated groups when compared with the control groups. Testicular histomorphometry revealed that, obestatin treatment caused a significant increase in the primary spermatocytes (P < 0.0001), secondary spermatocytes and spermatids (P < 0.005) and leydig cells population (p < 0.0001) both after 5 and 15 days. These findings indicated that obestatin can be a stimulator of testicular functions.Key words: Obestatin, male reproduction, testis, rats

Paramedic-conducted Mental Health Counselling for Abused Women in Rural Bangladesh: An Evaluation from the Perspective of Participants

This paper reports on evaluation of an initiative to use paramedics as the first-level mental health counsellors of abused women in rural Bangladesh (2003–2004) from the perspective of the abused women who participated in one or more counselling sessions. Thirty in-depth interviews, followed by a survey (n=372), targeted to cover all participants, were conducted in 2006. Overall, the arrangement, management of ethical issues, and skills of paramedics were rated favourably. Most (89%) abused women (n=372) considered the session useful; one-fourth of these women considered it very useful; and only a few abused women considered the session useless. Usefulness of the session was expressed mostly in terms of relief attained after talking about the issue. Most (87%) women reported being encouraged to be self-confident. In a context characterized by low self-confidence of women, lack of opportunity to talk about violence, and absence of professional mental health counselling services, this initiative is sufficiently promising to warrant further testing

Small-Molecule Host-Defense Peptide Mimetic Antibacterial and Antifungal Agents Activate Human and Mouse Mast Cells via Mas-Related GPCRs

Host-defense peptides (HDPs) have an important therapeutic potential against microbial infections but their metabolic instability and cellular cytotoxicity have limited their utility. To overcome these limitations, we utilized five small-molecule, nonpeptide HDP mimetics (smHDPMs) and tested their effects on cytotoxicity, antimicrobial activity, and mast cell (MC) degranulation. None of the smHDPMs displayed cytotoxicity against mouse 3T3 fibroblasts or human transformed liver HepG2 cells. However, one compound had both antifungal and antibacterial activity. Surprisingly, all five compounds induced degranulation in a human MC line, LAD2, and this response was substantially reduced in Mas-related G protein-coupled receptor (GPCR)-X2 (MRGPRX2)-silenced cells. Furthermore, all five compounds induced degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was abolished in cells expressing naturally occurring loss-of-function missense variants G165E (rs141744602) and D184H (rs372988289). Mrgprb2 is the likely mouse ortholog of human MRGPRX2, which is expressed in connective tissue MCs (CTMCs) such as cutaneous and peritoneal MCs (PMCs). All five smHDPMs induced degranulation in wild-type PMCs but not in cells derived from Mrgprb2-/-mice. These findings suggest that smHDPMs could serve as novel targets for the treatment of drug-resistant fungal and bacterial infections because of their ability to harness CTMCs’ host defense functions. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P\u3c0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcome

Serum Zinc level and liver pathological grading correlation in nonalcoholic steatohepatitis, in a University hospital in Tehran

Background: Nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis, fibrosis and liver cirrhosis. The oxidative stress enzymes are the diagnostic markers to prediction of histologic status of liver in nonalcoholic steatohepatitis disease. The aim of the study was to assessment of relationship between serum Zinc (Zn) levels with pathologic manifestation in patients with nonalcoholic steatohepatitis. Methods: This cohort study was done in patients with nonalcoholic steatohepatitis that had been visited in gastrointestinal clinic of Sina Hospital, Tehran, Iran from April, 2014 to April, 2015. Control group included the patients with no clinical manifestation of nonalcoholic steatohepatitis and normal liver ultrasonography, lab test and liver biopsy. Serum Zn level was measured with atomic absorption spectroscopy. Normal Serum level of Zn was considered 10.7-22.9 μmol/L (70-150 μg/dL) and less than 7 μg/dL was considered as Zn deficiency. Pathological findings were grading according to NAFLD activity score. Results: One hundred twenty patients were selected for the study in two equal groups. Six and 26 patients were excluded in case and control groups, respectively due to no consent to lab test. Finally, 54 patients (35 male/19 female) and 34 patients (22 male/12 female) in control group were participated in data analysis. The mean age on case and control group was 37.02±9.82 year and 33.24±12.01 year, respectively (P= 0.111). Zn level in case and control groups were 90.82±13.69 and 88.82±13.10, respectively. There were no statistically significant differences between two group in serum Zn level (P= 0.50). Also, there were no statistically significant differences between pathological grading in case group participants (steatosis: P= 0.640; Lobular inflammation: P= 0.882; fibrosis: P= 0.531). Conclusion: The finding of the study showed no significant association between serum zinc level and hepatic steatosis, lobular inflammation and fibrosis of the liver in nonalcoholic steatohepatitis. © 2016, Tehran University of Medical Sciences. All rights reserved