Current and future directions in frailty research.

The concept of frailty has been evolving dramatically for the past 30 years. Through its evolution, a variety of single and multidimensional models have been used to describe frailty. This article reviews the current literature related to the defining dimensions of frailty and identifies the gaps in the literature requiring additional research. A detailed literature review was performed to identify key dimensions and models currently being used to define frailty, classify interventions that have been developed to reverse frailty, and identify potential areas for future research within this field. Despite the large body of research defining the dimensions of frailty, no consensus exists on a comprehensive, operational definition. A standardized definition will be critical to design effective interventions at earlier stages along the continuum of frailty and interpret findings from evaluation studies. Identified gaps in the literature include studies supporting the utility of expanding the definition of frailty to incorporate social determinants, studies evaluating the role of obesity in the development of frailty, and the need for longitudinal studies for defining the pathways to developing frailty. This review highlights the need for an accurate definition of frailty and for longitudinal research to explore the development of frailty and evaluate the effectiveness of the frailty reversal interventions that may avert or delay adverse outcomes within this susceptible population. These future research needs are discussed within the context of the growing pressures to bring down health care costs, and the role of comparative effectiveness research and cost-effectiveness research in identifying interventions with the potential to help slow the growth of health care spending among the elderly

Evaluation of Sustainability of Prosthetic Services in a Post-Disaster Setting Case Study: Crudem Prosthetic Lab

Background: The earthquake in Haiti has led to 4000 people with amputations that will require extensive rehabilitation services over their lifetime. For an intervention such as providing prosthetics that is resource intensive, sustainability will play an important role in providing a long term impact. Research that evaluates the sustainability of the prosthetic service delivery model is necessary to identify the attributes that are best suited to ensure that acute and follow up care will be provided to the amputees in a coordinated manner. A prosthetic clinic was started in Milot in response to the earthquake in Haiti. Through the evaluation of this prosthetic clinic delivery and financing model, this study proposes to identify the barriers to improve delivery of care. The results of this study will be used to recommend strategies for establishing prosthetic clinics in low-resource settings. Research Design and Methods: Logic model methodology was used to evaluate sustainability of the clinic. A mixed methodology was used to collect data such as direct observation, qualitative and quantitative research methods. Barriers were identified in relation to provision of sustainability. Recommendations were developed to address the key barriers that were identified. Results: Recommendations were outlined to address the barriers such as technical performance, continuity of care and access: redesigning data infrastructure, improving patient discharge education, building a rehabilitation infrastructure and improving follow up of patients. An implementation plan for each strategy was outlined. Conclusions: The recommendations for improving sustainability are currently being adopted by the prosthetic lab management to change delivery of care

A qualitative IgG ELISA for detection of SARS-CoV-2-specific antibodies in Syrian hamster serum samples

Summary: This protocol describes an indirect enzyme-linked immunosorbent assay for qualitative detection of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian hamster serum samples. We describe the preparation of inactivated virus antigens and the negative control antigen and the use of antigen-coated microtiter plates to detect SARS-CoV-2-specific antibodies from SARS-CoV-2-infected hamsters, including the criteria for differentiating positive versus negative reaction. The limited batch-to-batch variability of this assay has been verified with two batches of independently prepared antigens.For complete details on the use and execution of this protocol, please refer to Mohandas et al. (2021)

Genomic characterization, transcriptome analysis, and pathogenicity of the Nipah virus (Indian isolate)

ABSTRACTNipah virus (NiV) is a high-risk pathogen which can cause fatal infections in humans. The Indian isolate from the 2018 outbreak in the Kerala state of India showed ~ 4% nucleotide and amino acid difference in comparison to the Bangladesh strains of NiV and the substitutions observed were mostly not present in the region of any functional significance except for the phosphoprotein gene. The differential expression of viral genes was observed following infection in Vero (ATCC® CCL−81™) and BHK−21 cells. Intraperitoneal infection in the 10–12-week-old, Syrian hamster model induced dose dependant multisystemic disease characterized by prominent vascular lesions in lungs, brain, kidney and extra vascular lesions in brain and lungs. Congestion, haemorrhages, inflammatory cell infiltration, thrombosis and rarely endothelial syncitial cell formation were seen in the blood vessels. Intranasal infection resulted in respiratory tract infection characterised by pneumonia. The model showed disease characteristics resembling the human NiV infection except that of myocarditis similar to that reported by NiV-Malaysia and NiV-Bangladesh isolates in hamster model. The variation observed in the genome of the Indian isolate at the amino acid levels should be explored further for any functional significance

SARS-CoV-2 Delta Variant Pathogenesis and Host Response in Syrian Hamsters

B.1.617 is becoming a dominant Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) lineage worldwide with many sublineages, of which B.1.617.2 is designated as a variant of concern. The pathogenicity of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 was evaluated and compared with that of B.1, an early virus isolate with D614G mutation in a Syrian hamster model. Viral load, antibody response, and lung disease were studied. There was no significant difference in the virus shedding pattern among these variants. High levels of SARS-CoV-2 sub genomic RNA were detected in the respiratory tract of hamsters infected with the Delta variant for 14 days, which warrants further transmission studies. The Delta variant induced lung disease of moderate severity in about 40% of infected animals, which supports the attributed disease severity of the variant. Cross neutralizing antibodies were detected in animals infected with B.1, Delta, and B.1.617.3 variant, but neutralizing capacity was significantly lower with B.1.351 (Beta variant)

Protective Immunity of the Primary SARS-CoV-2 Infection Reduces Disease Severity Post Re-Infection with Delta Variants in Syrian Hamsters

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Delta variant has evolved to become the dominant SARS-CoV-2 lineage with multiple sub-lineages and there are also reports of re-infections caused by this variant. We studied the disease characteristics induced by the Delta AY.1 variant and compared it with the Delta and B.1 variants in Syrian hamsters. We also assessed the potential of re-infection by these variants in Coronavirus disease 2019 recovered hamsters 3 months after initial infection. The variants produced disease characterized by high viral load in the respiratory tract and interstitial pneumonia. The Delta AY.1 variant produced mild disease in the hamster model and did not show any evidence of neutralization resistance due to the presence of the K417N mutation, as speculated. Re-infection with a high virus dose of the Delta and B.1 variants 3 months after B.1 variant infection resulted in reduced virus shedding, disease severity and increased neutralizing antibody levels in the re-infected hamsters. The reduction in viral load and lung disease after re-infection with the Delta AY.1 variant was not marked. Upper respiratory tract viral RNA loads remained similar after re-infection in all the groups. The present findings show that prior infection could not produce sterilizing immunity but that it can broaden the neutralizing response and reduce disease severity in case of reinfection

Possible Role of Accessory Proteins in the Viral Replication for the 20I/501Y.V1 (B.1.1.7) SARS CoV-2 Variant

The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) has been a global concern. The B.1.1.7 variant of SARS CoV-2 is reported to cause higher transmission. The study investigates the replication cycle and transcriptional pattern of the B.1.1.7 to hypothesis the possible role of different genes in viral replication. It was observed that the B.1.1.7 variant required a longer maturation time. The transcriptional response demonstrated higher expression of ORF6 and ORF8 compared to nucleocapsid transcript till the eclipse period which might influence higher viral replication. The number of infectious viruses titer is higher in the B.1.1.7, despite a lesser copy number than B.1, indicating higher transmissibility. The experimental evidence published linked ORF6 and ORF8 to play important role in replication and we also observed their higher expression. This leads us to hypothesis the possible role of ORF6 and ORF8 in B.1.1.7 higher replication which causes higher transmission

Differential Cell Line Susceptibility to the SARS-CoV-2 Omicron BA.1.1 Variant of Concern

The unique mutations of the SARS-CoV-2 Omicron variant are associated with increased transmissibility, immune escape, increased binding affinity to ACE-2, and increased viral load. Omicron exhibited a shift in tropism infecting the upper respiratory tract compared to other variants of concern which have tropism for the lower respiratory tract. The tropism of omicron variants in cell lines of different hosts and tissue origins still remains unclear. Considering this, we assessed the susceptibility of different cell lines to the SARS-CoV-2 omicron BA.1.1 variant and permissiveness among different cell lines for omicron replication. Susceptibility and permissiveness of a total of eleven cell lines, including six animal cell lines and five human cell lines for omicron BA.1.1 infection, were evaluated by infecting individual cell lines with omicron BA.1.1 isolate at a 0.1 multiplicity of infection. Virus replication was assessed by observation of cytopathic effects followed by viral load determination by real-time PCR assay and virus infectivity determination by TCID50 assay. The characteristic cytopathic effect, increased viral load, and productive omicron replication was detected in Vero CCL-81, Vero E6, Vero/hSLAM, MA-104, and Calu-3 cells. Although LLC MK-2 cells showed an increased TCID50 titer at the second infection, the viral load did not show much difference in both infections. Caco-2 cells did not show evident CPE, but they supported omicron replication at a low level. A549, RD, MRC-5, and BHK-21 cells supported omicron BA.1.1 replication without the CPE. This is the first study on the comparison of susceptibility of different cell lines to Omicron variant BA.1.1, which might be useful for future studies on emerging SARS-CoV-2 variants