FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD

Does the new cooperative medical scheme reduce inequality in catastrophic health expenditure in rural China?

Background In 2003, the New Cooperative Medical Scheme (NCMS) was introduced in China to re-establish health insurance for the country’s vast rural population. In addition, the coverage of NCMS has been expanding after the new health care reform launched in 2009. This study aims to examine whether the NCMS and its recent expansion have reached the goal of reducing the risk and inequality of catastrophic health spending for rural residents in China. Methods We conducted a face-to-face household survey in three counties of the Shandong province in 2009 and 2012. Using this unique panel data, we examined the changes in the incidence and intensity of catastrophic health expenditures (CHEs) before and after NCMS reimbursement. We used concentration index (CI) and decomposition method to study the changes in inequality in CHEs. Results We found that NCMS reimbursement played a role of reducing both the incidence and intensity of CHEs, and that this impact was stronger after the new health care reform was launched. After reimbursement, the concentration indices for CHEs were 0.073 and 0.021 in 2009 and 2012, indicating that the rich had a greater tendency to incur CHEs and there existed less inequality in the incidence of CHEs after reimbursement in 2012 compared with 2009. The decomposition analysis results suggested that changes in CHE inequality between 2009 and 2012 were attributed to changes in economic status and household size rather than reimbursement levels. Conclusions Our results indicated that inequality was shrinking from 2009 to 2012, which could be a result of fewer rich people having CHEs in 2012 compared with 2009. The impact of NCMS in alleviating the financial burden of rural residents was still limited, especially among the poor. Health care reform policies in China that aim to reduce CHEs must continue to place an emphasis on improving reimbursement, cost containment, and reducing income inequalities

TDP-43 Liquid-Liquid Phase Separation (LLPS) Deficiency Attenuates Amyloid Beta Deposition in the 5XFAD Transgenic Mouse Model of Alzheimer\u27s Disease

Background: TAR DNA-binding protein 43 (TDP-43) can be found within the cell nucleus in most tissues and is a fundamental component to protein production, as it works to slice and reconfigure mRNA molecules. Recently, TDP-43 inclusions have been identified as a prevalent proteinopathy in the brains of individuals diagnosed with Alzheimer\u27s Disease (AD). However, despite the growing body of evidence demonstrating the important role of TDP-43 in AD pathogenesis, whether and how TDP-43 proteinopathy and other AD pathological hallmarks interact remain largely unknown. Furthermore, TDP-43 has a high propensity to undergo liquid-liquid phase separation (LLPS), a biological process necessary for the condensation of proteins, nucleic acids, and other biomolecules. Purpose of Research: The correlation between TDP-43 LLPS and AD deposition is an intriguing, yet currently unexplored area of interest. The purpose of this study is to investigate whether and how TDP-43 and its phase separation are involved in amyloid deposition in APP transgenic mice for Alzheimer\u27s Disease. Methods: We crossed our recently generated mice expressing endogenous LLPS-deficient murine TDP-43 with the widely used 5XFAD transgenic mouse model. Different approaches were then performed to assess amyloid deposition and associated neuroinflammation. Results: When compared to 5XFAD mice, 5XFAD mice expressing LLPS-deficient TDP-43 showed significantly reduced amyloid deposition throughout the brain. Neuroinflammation, as evaluated by GFAP and Iba1 expression was also alleviated by LLPS-deficient TDP-43. Conclusion: For the first time, our study demonstrates the likely role TDP-43 LLPS plays in amyloid deposition. And, targeting TDP-43 LLPS may serve as a novel therapeutic approach to Alzheimer\u27s Disease treatment.https://digitalcommons.unmc.edu/surp2021/1036/thumbnail.jp

Geographic Distribution and Risk Factors of the Initial Adult Hospitalized Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in Mainland China

Background: As of 31st March 2010, more than 127,000 confirmed cases of 2009 pandemic influenza A (H1N1), including 800 deaths, were reported in mainland China. The distribution and characteristics of the confirmed cases in the initial phase of this pandemic in this country are largely unknown. The present study aimed to characterize the geographic distribution and patient characteristics of H1N1 infection in the 2009 pandemic as well as to identify potential risk factors associated with adverse patient outcome in China, through retrospective analyses of 885 hospitalized cases with confirmed H1N1 infection. Methodology/Principal Findings: The proportional hazards model was employed to detect risk factors for adverse outcome; the geo-statistical maps were used to characterize the distribution of all 2668 confirmed H1N1 patients throughout mainland China. The number of new cases increased slowly in May, 2009, but rapidly between June and August of the year. Confirmed cases were reported in 26 provinces; Beijing, Guangdong, Shanghai, Zhejiang and Fujian were the top five regions of the incidence of the virus infection. After being adjusted for gender, age, chronic pulmonary disease and other general symptoms, delay for more than two days before hospital admission (HR: 0.6; 95%CI: 0.5–0.7) and delayed onset of the H1N1-specific respiratory symptoms (HR: 0.3; 95%CI: 0.2–0.4) were associated with adverse patient outcome. Conclusions/Significance: The 2009 pandemic influenza A affected east and southeast coastal provinces and most populous cities more severely than other regions in mainland China due to higher risk of high level traffic-, high population density-, and high population mobility-associated H1N1 transmission.The clinical symptoms were mild in the initial phase of infection. Delayed hospital admission and delayed appearance of respiratory symptoms were among the major risk factors for poor patient outcome. These findings may have significant implications in the future pandemic preparedness and response

The effects of different tensile parameters for the neurodynamic mobilization technique on tricipital muscle wet weight and MuRf-1 expression in rabbits with sciatic nerve injury

BACKGROUND: After peripheral nerve injury, muscles without innervation begin to undergo atrophy. Research has suggested that MuRf-1 may play a role in muscle atrophy. The neurodynamic mobilization technique (NMT) is a manual therapy method used to elongate a nerve along its long axis, resulting in improved blood flow to the nerve. However, the nerve can be damaged if elongated too much. The purpose of this study is to observe the effect of NMT on muscle wet weight and MuRf-1 expression in rabbits with sciatic nerve injury. METHODS: Six adult rabbits were measured to determine the relationship between the joint angle of the lower limb and percent of sciatic nerve elongation to define the tensile parameters of NMT; Thirty adult rabbits were randomly assigned into a sham, model, NMT-A, NMT-B, or NMT-C groups. Four weeks post-treatment, the wet mass of the tricipital muscles and MuRf-1 expression were observed. RESULTS: The wet mass of the tricipital muscles in the NMT-B group was significantly greater than the NMT-A, NMT-C, and model groups. In addition, MuRf-1 expression was significantly reduced in the NMT-B group compared with the NMT-A, NMT-C, and model groups. CONCLUSIONS: Elongating the nerve by NMT of 9% in rabbits decreased MuRf-1 expression and decelerated muscle atrophy in the subjects with sciatic nerve injury

Comparisons of diabetic retinopathy events associated with glucose‐lowering drugs in patients with type 2 diabetes mellitus: A network meta‐analysis

Aim To assess the comparative effects of glucose‐lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random‐effects pairwise and network meta‐analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta‐analysis found that DPP‐4i (OR, 1.20; 95% CI, 0.87‐1.65), GLP‐1RA (OR, 1.19; 95% CI, 0.94‐1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49‐1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP‐4i in the pairwise meta‐analysis (OR, 1.27; 95% CI, 1.05‐1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01‐2.76). Conclusions Current evidence indicates that the association between DPP‐4i, GLP‐1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in large‐scale, well‐designed studies

TDP-43 Phase Separation Does Not Likely Regulate LPS-Induced Neuroinflammation

Immunohistochemistry (IHC) was performed to assess whether Transactive response Deoxyribonucleic acid binding Protein 43 (TDP-43) liquid-liquid phase separation (LLPS) regulates lipopolysaccaride (LPS)-induced neuroinflammation. Quantification and intensity results of glia cells and cytokines indicate that TDP-43 LLPS does not likely regulate LPS-induced neuroinflammation.https://digitalcommons.unmc.edu/surp2021/1060/thumbnail.jp

Kaposi’s Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (MyD88) Expression via Modulation of Its RNA

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of MyD88, and physiological levels of MyD88 are downregulated during KSHV lytic replication when RTA is expressed. The N-terminal region of RTA is required for the reduction of MyD88. Additional studies demonstrated that RTA targets MyD88 expression at the RNA level, inhibits RNA synthesis of MyD88, and may bind MyD88 RNA. Finally, RTA inhibits IL-1-mediated activation of NF-B. Because IL-1 is abundant in the KS microenvironment and inhibits KSHV replication, this work may expand our understanding of how KSHV evades host inflammation and immunity for its survival in vivo

Kaposi’s Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (MyD88) Expression via Modulation of Its RNA

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of MyD88, and physiological levels of MyD88 are downregulated during KSHV lytic replication when RTA is expressed. The N-terminal region of RTA is required for the reduction of MyD88. Additional studies demonstrated that RTA targets MyD88 expression at the RNA level, inhibits RNA synthesis of MyD88, and may bind MyD88 RNA. Finally, RTA inhibits IL-1-mediated activation of NF-B. Because IL-1 is abundant in the KS microenvironment and inhibits KSHV replication, this work may expand our understanding of how KSHV evades host inflammation and immunity for its survival in vivo

Kaposi’s Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (MyD88) Expression via Modulation of Its RNA

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of MyD88, and physiological levels of MyD88 are downregulated during KSHV lytic replication when RTA is expressed. The N-terminal region of RTA is required for the reduction of MyD88. Additional studies demonstrated that RTA targets MyD88 expression at the RNA level, inhibits RNA synthesis of MyD88, and may bind MyD88 RNA. Finally, RTA inhibits IL-1-mediated activation of NF-B. Because IL-1 is abundant in the KS microenvironment and inhibits KSHV replication, this work may expand our understanding of how KSHV evades host inflammation and immunity for its survival in vivo