Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V

Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid- dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506- FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC.     

Exotic and indigenous problem plants species used,by the Bapedi,to treat sexually transmitted infections in Limpopo Province,South Africa

Background

The ethnic usage of exotics and indigenous problem plants is a highly debated topic, as legislative requirements over-shadow their potential medicinal value, particularly to treat sexually transmitted infections (STIs). Limited information exists regarding their medicinal value among the Bapedi.

Objectives

To ascertain the importance of exotics and indigenous problem plants in the treatment of STIs, a major global primary health care challenge.

Methods

A field observation and semi-structured questionnaire focussing on species diversity, types of STIs treated and medicinal preparation as well as application was used to collect data from 34 traditional healers.

Results

Seven exotics and three indigenous problem species were identified. These species were used to treat four STIs; with Catharanthus roseus illustrating its dominance in the treatment of gonorrhoea. Some medicinal species used by Bapedi traditional healers have been validated through scientific research or through their extensive use by various cultures in South Africa and other parts of Africa. To the best of our knowledge Alternanthera pungens, Caesalpinia decapetala, Cinnamomum verum, and Citrullus lanatus are reported for the first time in the treatment of the investigated STIs.

Conclusions

Exotic and indigenous problem species constitute an important component of the STIs treatment protocol. Their utilization by Bapedi cautions against the narrow-minded approach of indiscriminate eradication, as these species can play a significant role in the primary health care needs of socio-economic vulnerable people.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.     

Natural product diversity from the endophytic fungi of the genus Aspergillus

The endophytic fungus Aspergillus is considered as an enormous source of chemical leads with promising biological activities. Different Aspergillus species have proved their ability to produce plenty of secondary metabolites including butenolides, alkaloids, terpenoids, cytochalasins, phenalenones, ρ-terphenyls, xanthones, sterols, diphenyl ether and anthraquinone derivatives with diverse biological activities, such as anti-cancer, antifungal, anti-bacterial, anti-viral, anti-inflammatory, antitrypanosomal and antileishmanial activities. From January 2015 until December 2019, three hundred and sixty-one secondary metabolites were reported from different endophytic Aspergillus species. This review discusses the isolated secondary metabolites from different endophytic Aspergillus species reported from January 2015 to December 2019 along with their reported biological activities and structural aspects whenever applicable.

The endophytic fungus Aspergillus is the precious source of chemical biodiversity.     

Efficacy of osteopathy and other manual treatment approaches for malocclusion – A systematic review of evidence

Backgroundand objectivesThe osteopathic literature often underlines the need for manual treatment of malocclusion. This literature review will investigate the efficacy of osteopathic and other manual treatment approaches for malocclusion.Data sourcesA systematic literature review was undertaken by searching medical and osteopathic databases (Pubmed, DIMDI, Osteopathic Research Digital Repository, Physiotherapy Evidence Database (PEDro), www.chiroindex.org, www.osteopathic-research.com). Other relevant osteopathic journals that are not indexed (e.g. Osteopathische Medizin, Osteopathic Medicine and Primary Care) were also searched. The keywords ‘dental occlusion’ and ‘malocclusion’ were combined with keywords for various manual treatment approaches.Study selection and data extractionAs few hits were anticipated, the inclusion criteria were fairly wide and not too strict in terms of quality. Identified studies were categorized according to Sacketts' levels of evidence, and assessed using Downs and Black's quality checklist for healthcare interventions.ResultsOf 30 articles that met the inclusion criteria, 13 were experts' opinions with hardly any evidence. As such, this review focused on the remaining 17 studies: 12 case series, three case–control studies, one systematic review of case–control studies, and one methodologically weak randomized controlled trial. Most of the studies in this review were of poor quality. By applying Downs and Black's quality assessment tool problems with internal and external validity could be identified. Most of the studies had confounding or selection bias. Only three studies attained more than half of the maximum score on the Downs and Black's quality assessment tool.ConclusionsA few studies reported some changes in malocclusion associated with osteopathy and other manual treatment approaches. As such, there is a need for high-quality research in this area.     

The association between physical fitness level and number and severity of injury and illness in youth elite athletes

Youth elite athletes often double their training and competition load after enrollment into specialized sport academy high school programs. The least fit athletes may be exposed to an excessive and too rapid increase in training load, with negative adaptations such as injury and illness as a consequence. In this study, our aim was to determine whether these least fit athletes were at greater risk of injury or illness during their first school year. Participants were 166 youth elite athletes (72% boys) from a variety of team, technical, and endurance sports newly enrolled into specialized sport academy high schools. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used to self‐report injuries and illnesses weekly for 26 weeks. Athletes completed the Ironman Jr physical fitness test battery at baseline, evaluating endurance, strength, agility, and speed properties. We ranked the athletes based on their combined test scores and identified the least fit quartile. The main outcome was the number and severity of health problems, comparing the least fit quartile of athletes to the rest of the cohort. Overall, the least fit quartile of athletes did not report more health problems (mean 3.7, 95% CI 3.0‐4.4) compared with the rest of the cohort (3.6, 3.2‐3.9). In conclusion, we demonstrated no association between low physical fitness level and number and severity of injury and illness in youth elite athletes after enrollment into a specialized sport academy high school program.     

Implementation of the Adductor Strengthening Programme: Players primed for adoption but reluctant to maintain — A cross‐sectional study

Groin injuries represent a considerable problem in male football, accounting for 4%‐19% of all time‐loss injuries. The Adductor Strengthening Programme is the first groin‐specific prevention program shown to reduce the risk of groin problems. We aimed to use the RE‐AIM framework to examine the players’ experiences with the implementation of the program and player attitude toward groin injury prevention in football. Of the 632 players involved in the trial examining the effect of the Adductor Strengthening Programme, 501 agreed to participate in a survey at the end of the season. Most players thought that footballers are at moderate to high risk for groin injuries (87%) and that there is a need for preventive measures (96%). They also believed that a preventive program with strengthening exercises would reduce the risk of groin injuries (91%). Majority of the players reported using <5 minutes to complete the program (73%), and only 11% wanted additional exercises. However, only 46% reported to have performed the program as recommended, and an even smaller proportion (31%) planned to continue using it as recommended the next season. Our results suggest that footballers believe that prevention of groin injuries is needed. Attitude toward implementation of the Adductor Strengthening Programme was positive, and the single‐exercise approach was considered an important facilitator. However, in future dissemination of the program, the players’ reluctance to maintain the exercise protocol may be a potential barrier to implementation that should be addressed.