Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension

Cerium oxide (CeO₂) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO₂ nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO₂ nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO₂ groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO₂ nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO₂ nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, β-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO₂ nanoparticle administration may attenuate the hypertrophic response of the heart following PAH.     

Evaluation of Antioxidant Enzymes Activity and Malondialdehyde Levels in Patients With Chronic Periodontitis and Diabetes Mellitus

Background: The aim of this study is to investigate the impact of diabetes, a known risk factor for periodontitis, on activities of antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) as well as levels of free radical damage marker malondialdehyde (MDA) in blood and saliva of individuals with chronic periodontitis (CP). Methods: Sixty patients with CP (30 patients with type 2 diabetes mellitus [DMCP] and 30 systemically healthy patients [CP]) and 60 periodontally healthy individuals (30 patients with type 2 diabetes mellitus and 30 systemically healthy patients [PH]) were included in this study. After clinical measurements, blood and saliva samples were collected. SOD, GR, and CAT activities in red blood cell lysate and saliva and MDA levels in plasma and saliva samples were spectrophotometrically assayed. An analysis of variance test followed by a post hoc test was used to compare the intragroup and intergroup variances among the study groups. Results: MDA levels in both the periodontitis groups were higher than in the periodontally healthy groups, but the difference between the CP and DMCP groups did not reach statistical significance (P >0.05). There was a highly significant difference between the CP and PH groups for all the enzymes studied except for SOD in blood. Only salivary SOD and GR activities were significantly different in the CP and DMCP groups. Conclusions: This study favors the role of oxidative stress in both diabetes and periodontitis. It shows that the compensatory mechanism of the body is partially collapsed because of excessive production of free radicals during periodontitis and is not able to cope with increased free radical generation attributable to diabetes, thereby worsening the situation.     

Women’s Experiences with Intimate Partner Violence and Their Mental Health Status in India: A Qualitative Study of Sambalpur City

The intimate partner violence (IPV) against women has been identified as a violation of human rights and a serious public health concern. There is not only the immediate consequence of partner violence, such as injury or death but also the other long-term health consequences. IPV can be associated with psychological effects such as depressive disorder, posttraumatic stress disorder, and substance abuse. The study aims to explore the nature and causes of IPV on women’s life and their personal experiences to deal with. This is an NGO-based study. For better understanding of the issues, Purposive sampling was used in selecting women with clinically diagnosed mental illness who experienced IPV. The qualitative research methodology was employed to explore the experiences and impact of IPV on the mental health status of women. For analysis, we used a phenomenological approach and conducted in-depth interviews. Findings show the participating women were suffering from IPV in physical, psychological, and sexual forms. Majority of respondents felt that wife-beating and abusing was fairly common. Most of the women had to face violence on a frequent and occasional basis. IPV experienced women were facing a mental illness like anxiety, depression and sleeping-disorder. The women, who were facing mental illness due to IPV, have been and continue to be exposed to such violence. Despite being employed and suffering from IPV deeply, women choose to stay with their abusive partner because of their children future, lack of support, and social security. The mental health of victims’ was clinically diagnosed, including self-assessed symptoms. It means participants were aware that they are mentally ill because of IPV. The healthy and quick recovery treatment should be given according to the need of women, rather than providing comprehensive standardised treatment for all.     

A multicenter,open‐label,phase II study of tirabrutinib (ONO/GS‐4059) in patients with Waldenström’s macroglobulinemia

Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88^L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646).     

Evaluation of an ASFV RNA Helicase Gene A859L for Virus Replication and Swine Virulence

African swine fever virus (ASFV) is producing a devastating pandemic that, since 2007, has spread to a contiguous geographical area from central Europe to Asia. In July 2021, ASFV was detected in the Dominican Republic, the first report of the disease in the Americas in more than 40 years. ASFV is a large, highly complex virus harboring a large dsDNA genome that encodes for more than 150 genes. The majority of these genes have not been functionally characterized. Bioinformatics analysis predicts that ASFV gene A859L encodes for an RNA helicase, although its function has not yet been experimentally assessed. Here, we evaluated the role of the A859L gene during virus replication in cell cultures and during infection in swine. For that purpose, a recombinant virus (ASFV-G-∆A859L) harboring a deletion of the A859L gene was developed using the highly virulent ASFV Georgia (ASFV-G) isolate as a template. Recombinant ASFV-G-∆A859L replicates in swine macrophage cultures as efficiently as the parental virus ASFV-G, demonstrating that the A859L gene is non-essential for ASFV replication. Experimental infection of domestic pigs demonstrated that ASFV-G-∆A859L replicates as efficiently and induces a clinical disease indistinguishable from that caused by the parental ASFV-G. These studies conclude that the predicted RNA helicase gene A859L is not involved in the processes of virus replication or disease production in swine.     

Epidemiology and Genetic Diversity of PCV2 Reveals That PCV2e Is an Emerging Genotype in Southern China: A Preliminary Study

Porcine circovirus-associated disease (PCVAD), caused by porcine circovirus type 2 (PCV2), has ravaged the pig industry, causing huge economic loss. At present, PCV2b and PCV2d are highly prevalent genotypes worldwide, while in China, in addition to PCV2b and PCV2d, a newly emerged PCV2e genotype detected in the Fujian province has attracted attention, indicating that PCV2 genotypes in China are more abundant. A preliminary study was conducted to better understand the genetic diversity and prevalence of PCV2 genotypes in southern China. We collected 79 random lung samples from pigs with respiratory signs, from 2018 to 2021. We found a PCV2-positivity rate of 29.1%, and frequent co-infections of PCV2 with PCV3, Streptococcus suis (S. suis), and other porcine pathogens. All PCV2-positive samples were sequenced and subjected to whole-genome analysis. Phylogenetic analysis, based on the PCV2 ORF2 gene and complete genomes, found that PCV2 strains identified in this study belonged to genotypes PCV2a (1), PCV2b (6), PCV2d (10), and PCV2e (6). Importantly, PCV2e was identified for the first time in some provinces, including Guangdong and Jiangxi. Additionally, we found two positively selected sites in the ORF2 region, located on the previously reported antigenic epitopes. Moreover, codon 63, one of the positively selected sites, has different types of amino acids in different genotypes. In conclusion, this study shows that PCV2e is an emerging genotype circulating in southern China, which warrants urgent, specific surveillance to aid the development of prevention and control strategies in China.     

A comprehensive review on the sources,essentiality and toxicological profile of nickel

This review contains up-to-date knowledge and recent advancements on the essentiality, sources, and toxicological profile of nickel and its different compounds. Nickel is a recognized essential element for several important biological processes like the healthy growth of plants, animals, and soil/water microbes; though an excess amount of nickel intoxicates flora and fauna. Nickel is found to affect the photosynthetic function of higher plants; it can severely degrade soil fertility and causes many chronic diseases in humans. Due to the huge growth in the nickel industry and consumption of nickel-containing products, environmental pollution has become inevitable by the element nickel and also varieties of its by-products through all the phases of making, utilization and dumping. We have focused on the importance of agenda 2030 (UN 17 SDGs) during the preparation of the write-up and have highlighted goals 3, 6, 8, 9, 11, 12, 13, 14, and 15 by elaborately discussing associated points. The plausible molecular mechanism of nickel toxicity is presented in simple diagrams. The article elaborates on possible methods for remediation of nickel toxicity and the treatment of nickel dermatitis and nickel cancer. Recent advancements in the understanding of the dual aspects of nickel as beneficial and a carcinogen are the key subject of this article.

This review contains up-to-date knowledge and recent advancements on the essentiality, sources, and toxicological profile of nickel and its different compounds.     

Targets of immunotherapy for hepatocellular carcinoma: An update

Hepatocellular carcinoma, the most common primary liver cancer, in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages. Although, surgical resection, ablation, liver transplant, and locoregional therapies are available for early stages; however, there are yet no effective treatment for advanced and recurrent tumors. Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression. However, still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment. At present, the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy, immune checkpoint therapy, adoptive cell transfer therapy, and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells. This review discusses the recent key development, the basis of drug resistance, immune evasion, immune tolerance, the available therapies based on stage of the tumor, and the ongoing clinical trials on immune checkpoint inhibitor therapy, adoptive cell transfer therapy, oncolytic viral vaccine therapy, and combination therapy.     

A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18–50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery. Prospective consent was obtained for the use of excess tissue from patients undergoing lumpectomy or mastectomy for breast carcinoma. Tissue blocks from nine breast carcinomas were serially sectioned. Hematoxylin and eosin‐stained slides at 100 μm intervals were scanned using a Nanozoomer (Hamamatsu, Japan) microscopic‐resolution scanner. Three‐dimensional reconstructions of tumors were created from scanned images using Reconstruct, open‐access software. Breast carcinoma subtypes demonstrated characteristic growth patterns within breast tissue, which may have implications for lumpectomy surgery. Invasive ductal carcinomas showed a spherical shape, with a spiculated surface representing tumor cells infiltrating into surrounding parenchyma. Ductal carcinoma in situ appeared to spread along the duct system, creating dilated, tortuous, tumor‐filled ducts. The invasive lobular carcinomas examined had a haphazard, linear, infiltrative growth pattern, different from the shape seen in ductal carcinomas. Our preliminary work suggests that invasive ductal and invasive lobular carcinomas appear to have distinct growth patterns in three dimensions and ductal carcinoma in situ appears to grow in a linear fashion along the duct network. The microanatomy studies described have the potential to guide refinements in breast lumpectomy technique.     

Modeling the economic benefit of targeted mild hypothermia in deceased donor kidney transplantation

Delayed graft function (DGF) in kidney transplant significantly increases inpatient and outpatient cost. Targeted, mild hypothermia in organ donors after neurologic determination of death significantly reduced the rate of DGF in a recent randomized controlled clinical trial. To assess the potential economic benefit of national implementation of donor hypothermia, rates of reduction DGF were combined with estimates of the impact of DGF on hospital cost and total health expenditure for standard and extended criteria donor organs (SCD and ECD). DGF increases the cost of the transplant episode by $9487 for ECD transplant and $10 342 for SCD transplant. Medicare recipients with DGF incur an additional $18 513 spending for ECD and $14 948 in SCD transplants over the first year. An absolute reduction in DGF rate after kidney transplantation consistent with trial results (ECD 25%, SCD 7%) has the potential to lower annual hospital cost for kidney transplant by $13 178 746 and annual Medicare spending by $20 970 706 compared to standard donor management practice using static cold storage. Targeted mild hypothermia improves care of renal transplant patients by safely reducing DGF rates in both ECD and SCD transplant. Broader application of this safe, effective, and low‐cost intervention could reduce healthcare expenditures for providers and insurers.