P atellofemoral pain is a common problem which affects a large number of athletic and nonathletic people. Symptoms frequently associated with patellofem* ral problems are generalized anterior knee pain, patellofemoral joint crepitus, peripatellar swelling, and buckling or locking of the knee (30). The symptoms are often exacerbated by prolonged sitting with a bent knee, rising from a seated position, ascending and descending stairs and sloped surfaces, and kneeling (7,8).The etiology of this problem could be related to nontraumatic factors, such a 5 osseous abnormalities, muscle imbalances, laxity o r tightness of the ligaments or joint capsule, or direct traumatic injury to the joint. The focus of the present study was on nontraumatic patellofemoral joint dysfunction, specifically muscle imbalances.The biomechanics of the patellofemoral joint are controlled by its static and dynamic components. The static components include the configuration of the articular surfaces, the medial and lateral retinaculum, and the patellofemoral and patellotibial ligaments. The primary dynamic components are the four parts of the quadriceps femoris complex with accessory input from the iliotibial band (lo), the adductor magnus and Ionof patellofemoral pain are I) neurogus (3,13), the pes anserine group, muscular imbalances of the vastus and biceps femoris ( 18,29). medialis oblique (VMO) and the vasSome of the theories for the etitus lateralis (VL), 2) tightness of the ology of nontraumatic gradual onset lateral knee retinaculum, hamstrings, Imbalances in the firing pattern and contraction intensity of the vastus medialis oblique (VMO) and the vastus lateralis (VL) have been considered important factors contributing to patellofemoral joint dysfunction. Vastus medialis oblique and vastus lateralis electromyographic (EMG) activity were measured for 15 individuals without patellofemoral pain (asymptomatic group) and 13 subjects with patellofemoral pain (symptomatic group) while ascending and descending steps. The peak V M O M ratios of EMG activity and the difference in peak VMO and VL onset times were measured. Two-way mixed-model analyses of variance (ANOVA) were used to determine the main effects of group (asymptomatic and symptomatic), phase (concentric phase ascending and two eccentric phases descending stairs), and the interaction between group and phase. The ANOVAs indicated no difference between groups for the peak V M O M EMG ratio or for the onset timing between peak VMO and VL muscle activity. Combining groups, the peak V M O M EMG ratio was less for the eccentric weight acceptance phase of descent compared with
Background: Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i-6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge. Hepatitis C genotype is defined by interrogation of the sequence composition of the 5' untranslated region [5'UTR]. Occasionally, ambiguous specimens require further investigation of the genome, usually by interrogation of the NS5B region. The original purpose of this study was to confirm the existence of a suspected mixed genotype infection of genotypes 2 and 4 by clonal analysis at the NS5B region of the genome in two specimens from two separate individuals. This initial identification of genotype was based on analysis of the 5'UTR of the genome by reverse line probe hybridisation [RLPH].
Soon after the discovery of the hepatitis C virus (HCV), attention turned to the development of models whereby replication of the virus could be investigated. Among the HCV replication models developed, the HCV RNA replicon model and the newly discovered infectious cell culture systems have had an immediate impact on the study of HCV replication, and will continue to lead to important advances in our understanding of HCV replication. The aim of this study is to deal with developments in HCV replication models in a chronological order from the early 1990s to the recent infectious HCV cell culture systems.
Since the first report of genetically heterogeneous, or quasispecies, populations of RNA viruses, the genetic heterogeneity of the RNA genomes of major viral pathogens has been extensively studied. These studies aim to provide insights into the evolutionary pressures that act upon viruses, in order to define windows where anti-viral therapies will be most effective, to take prognostic values from viral genetic distributions at a given time, and to aid the development of novel therapeutic compounds that may tilt viral replication towards information loss. Many methodologies are employed to analyse genetic distributions of a virus in a given sample, but all involve the generation, and subsequent analysis, of the sequence information contained in a reverse-transcription-polymerase chain reaction (RT-PCR) product. Despite the fact that the aim of these RT-PCRs is to obtain sequence information from viral genomes, their application to this task is approached without adequate consideration of this end-goal. The establishment of an RT-PCR for a specific viral target genome generally proceeds in the same fashion as one would apply to establishing a PCR to determine the presence or absence of a specific target sequence in a given sample. However, it is becoming increasingly apparent that RT-PCR products generated by amplification with the ubiquitous thermostable DNA polymerase Taq, coupled with standard cloning and sequencing methodologies, has the potential to yield inaccurate and misleading data as pertains to the information content of populations of RNA viral genomes. This review discusses varying approaches employed to analyse heterogeneous populations of hepatitis C virus RNA genomes.
The COVID‐19 pandemic has placed unprecedented pressure on biopharmaceutical companies to develop efficacious preventative and therapeutic treatments, which is unlikely to abate in the coming years. The importance of fast progress to clinical evaluation for treatments, which tackle unmet medical needs puts strain on traditional product development timelines, which can take years from start to finish. Although previous work has been successful in reducing phase 1 timelines for recombinant antibodies, through utilization of the latest technological advances and acceptance of greater business risk or costs, substantially faster development is likely achievable without increased risk to patients during initial clinical evaluation. To optimize lessons learned from the pandemic and maximize multi‐stakeholder (i.e., patients, clinicians, companies, regulatory agencies) benefit, we conducted an industry wide benchmarking survey in September/October 2021. The aims of this survey were to: (i) benchmark current technical practices of key process and product development activities related to manufacturing of therapeutic proteins, (ii) understand the impact of changes implemented in COVID‐19 accelerated Ab programs, and whether any such changes can be retained as part of sustainable long‐term business practices and (iii) understand whether any accelerative action(s) taken have (negatively) impacted the wider development process. This article provides an in‐depth analysis of this data, ultimately highlighting an industry perspective of how biopharmaceutical companies can sustainably adopt new approaches to therapeutic protein development and production.
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