Advancing Medical Device and Biotech Innovations

M2D2 is a UMass Lowell – UMass Medical School Worcester initiative that helps entrepreneurs move new medical device and biotech ideas from patent to production and offers early-stage inventors and established companies easy, affordable and coordinated access to world-class researchers and resources at both the Lowell and Worcester campuses. UMass Lowell and UMass Worcester extend use of engineering and scientific resources to M2D2 companies. These core resources are available to researchers by using the research services agreement. The use of UMass Lowell and UMass Worcester interns and faculty is an enormous benefit to an emerging medical device or biotech company. UMass Worcester’s campus offers access to core research supports and highly trained personnel to efficiently conduct animal or clinical studies across the life cycle of projects. UMass Lowell has two M2D2 facilities with private and shared wet lab space, equipment, office space and conference rooms. It offers business and medical feasibility assessments, product development, medical and clinical pathway assistance, SBIR and STTR research partnerships and access to capital. M2D2 was established with seed funding from the UMass President’s Office, the Mass Life Sciences Center and the Commonwealth of Massachusetts

Specific Cellular Immune Response and Cytokine Patterns in Patients Coinfected with Hepatitis C Virus and Schistosoma mansoni

Patients coinfected with hepatitis C virus (HCV) and Schistosoma mansoni show high incidence of viral persistence and accelerated fibrosis. To determine whether immunological mechanisms are responsible for this alteration in the natural history of HCV, the HCV-specific peripheral CD4+ T cell responses and cytokines were analyzed in patients with chronic hepatitis C monoinfection, S. mansoni monoinfection, or HCV and S. mansoni coinfection. An HCV-specific CD4+ proliferative response to at least 1 HCV antigen was detected in 73.3% of patients infected with HCV, compared with 8.6% of patients coinfected with HCV and S. mansoni. Stimulation with HCV antigens produced a type 1 cytokine profile in patients infected with HCV alone, compared with a type 2 predominance in patients coinfected with HCV and S. mansoni. In contrast, there was no difference in response to schistosomal antigens in patients infected with S. mansoni alone, compared with those coinfected with HCV and S. mansoni. These findings suggest that the inability to generate an HCV-specific CD4+/Th1 T cell response plays a role in the persistence and severity of HCV infection in patients with S. mansoni coinfectio

Kinetics of Intrahepatic Hepatitis C Virus (HCV)-Specific CD4+ T Cell Responses in HCV and Schistosoma mansoni Coinfection: Relation to Progression of Liver Fibrosis

The kinetics of intrahepatic hepatitis C virus (HCV)-specific CD4+ T cell responses and their role in progression of fibrosis have not previously been characterized. Subjects with HCV/Schistosoma mansoni coinfection have a more rapid progression of HCV liver fibrosis than do those with HCV infection alone. The present prospective longitudinal study compared the liver histology, HCV-specific intrahepatic and peripheral CD4+ T cell proliferative responses, and cytokines (enzyme-linked immunospot) in 48 subjects with unresolved acute HCV infection with or without S. mansoni coinfection, at 6-10 months after acute infection and at the end of follow-up ( months), and the findings were correlated 96±8.7 to the rate of progression of fibrosis per year. Coinfected subjects had significant worsening of fibrosis, compared with subjects with HCV infection alone. At baseline, subjects with HCV infection alone had stronger multispecific intrahepatic HCV-specific CD4+ T helper 1 responses than did coinfected subjects, who had either no responses or weak, narrowly focused responses, and, over time, these T cell responses were maintained only in the liver. The rate of progression of fibrosis and virus load inversely correlated with intrahepatic HCV-specific CD4+ T cell response. The present prospective analysis indicates that enhancement of progression of liver fibrosis is associated with failure to develop early, multispecific, HCV-specific CD4+ Th1 responses, suggesting that novel therapeutic approaches inducing strong cellular immune responses might limit subsequent liver damage in individuals with chronic hepatitis

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Background ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID. Methods Patients with fatigue-dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical-based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two-week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849. Findings Between December 15th 2021, and May 23th 2022, 60 participants were screened, and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious or led to treatment discontinuation. Interpretation Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there were significant improvements in fatigue-based symptoms among patients living with Long COVID following a four-week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. Funding Axcella Therapeutics

Peginterferon Alfa-2a plus Ribavirin versus Interferon Alfa-2a plus Ribavirin for Chronic Hepatitis C in HIV-Coinfected Persons

Chronic hepatitis C virus (HCV) infection is a cause of major complications in persons who are also infected with the human immunodeficiency virus (HIV). However, the treatment of HCV infection in such persons has been associated with a high rate of intolerance and a low rate of response. We conducted a multicenter, randomized trial comparing peginterferon plus ribavirin with interferon plus ribavirin for the treatment of chronic hepatitis C in persons coinfected with HIV

Latin American Consensus: Children Born Small for Gestational Age

72-87Cuatrimestra

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

MassTERi: Promoting Translational Research and Entrepreneurship at the University of Massachusetts Medical School

MassTERi is a faculty-led initiative to foster entrepreneurship among UMass Medical School students, postdocs and faculty, and facilitate translation of UMMS discoveries into drugs, products, technologies and companies. The mission of MassTERi is to; foster a culture of entrepreneurship at UMass Medical School and facilitate dynamic partnerships with industry; bridge the gap between UMMS discoveries and their development into drugs, products, technologies and companies; educate and nurture the next generation of translational scientists and entrepreneurs; benefit the public good through development and commercialization of new therapies and creation of high-value life science jobs. We will present information about MassTERi and our programs