Osteoarthritis year in review 2019: rehabilitation and outcomes.

OBJECTIVE: Inactivity and obesity are risk factors for osteoarthritis (OA) progression. The purpose of this review was to highlight intervention parameters of exercise and lifestyle diet interventions on clinical outcomes in OA that were published over 15 months, starting January 1, 2018. DESIGN: Systematic literature searches were performed in Medline (Pubmed, OVID), Scopus, CINAHL, CENTRAL and Embase from January 1, 2018 to April 1, 2019. Key words included osteoarthritis, exercise, physical activity, diet and nutrition. Randomized controlled designs and data synthesis papers (systematic reviews, meta-analyses, clinical guidelines) written in English, that included humans with OA of any joint were included. Trials were evaluated using the Physiotherapy Evidence Database (PEDro) critical appraisal tool and the Template for Intervention Description and Replication (TIDieR). Systematic reviews and meta-analyses were evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). Intervention details (RCTs) and key finding from papers were summarized. RESULTS: Of 540 titles and abstracts retrieved, 147 full articles were reviewed and 53 met the inclusion criteria, comprised of 39 RCTs and 14 synthesis papers. By addressing inactivity, exercise effectively improves clinical outcomes and, based on low-moderate quality evidence, without further damage to cartilage or synovial tissue. By comparison, much less work focused on minimizing obesity. Diet must be combined with exercise to improve pain, but alone, can improve physical function. CONCLUSIONS: Future work is necessary to identify the ideal exercise frequency and intensity and lifestyle diet intervention parameters. Improved adherence to reporting guidelines in future work will greatly enhance the OA rehabilitation field.

Biomechanical effects of valgus knee bracing: a systematic review and meta-analysis.

To review and synthesize the biomechanical effects of valgus knee bracing for patients with medial knee osteoarthritis (OA). Electronic databases were searched from their inception to May 2014. Two reviewers independently determined study eligibility, rated study quality and extracted data. Where possible, data were combined into meta-analyses and pooled estimates with 95% confidence intervals (CI) for standardized mean differences (SMD) were calculated. Thirty studies were included with 478 subjects tested while using a valgus knee brace. Various biomechanical methods suggested valgus braces can decrease direct measures of medial knee compressive force, indirect measures representing the mediolateral distribution of load across the knee, quadriceps/hamstring and quadriceps/gastrocnemius co-contraction ratios, and increase medial joint space during gait. Meta-analysis from 17 studies suggested a statistically significant decrease in the external knee adduction moment (KAM) during walking, with a moderate-to-high effect size (SMD = 0.61; 95% CI: 0.39, 0.83; P < 0.001). Meta-regression identified a near-significant association for the KAM effect size and duration of brace use only (ß, -0.01; 95% CI: -0.03, 0.0001; P = 0.06); with longer durations of brace use associated with smaller treatment effects. Minor complications were commonly reported during brace use and included slipping, discomfort and poor fit, blisters and skin irritation. Systematic review and meta-analysis suggests valgus knee braces can alter knee joint loads through a combination of mechanisms, with moderate-to-high effect sizes in biomechanical outcomes.

Memorability of Visual Features in Network Diagrams.

We investigate the cognitive impact of various layout features-symmetry, alignment, collinearity, axis alignment and orthogonality - on the recall of network diagrams (graphs). This provides insight into how people internalize these diagrams and what features should or shouldn't be utilised when designing static and interactive network-based visualisations. Participants were asked to study, remember, and draw a series of small network diagrams, each drawn to emphasise a particular visual feature. The visual features were based on existing theories of perception, and the task enabled visual processing at the visceral level only. Our results strongly support the importance of visual features such as symmetry, collinearity and orthogonality, while not showing any significant impact for node-alignment or parallel edges.

Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage.

Activated protein C (APC) resistance, both in its congenital form, due to the factor V Leiden mutation, and in its acquired form, are important risk factors for systemic venous thrombosis. In view of the suspected thrombotic aetiology of some cases of recurrent miscarriage, the prevalence of APC resistance was determined among 1111 consecutive Caucasian women with a history of either recurrent early miscarriage (three or more consecutive pregnancy losses at <12 weeks gestation; n = 904) or a history of at least one late miscarriage (>12 weeks gestation; n = 207). A control group of 150 parous Caucasian women with no previous history of adverse pregnancy outcome was also studied. Acquired APC resistance was significantly more common among both women with recurrent early miscarriage (8.8%: 80/904; P = 0.02) and those with late miscarriage (8.7%: 18/207; P = 0.04) compared with controls (3.3%: 5/150). In contrast, the frequency of the factor V Leiden allele was similar among (i) women with recurrent early miscarriage (3.3%:60/1808; 58 heterozygotes and one homozygote), (ii) those with late miscarriage (3.9%:16/414; 14 heterozygotes and one homozygote) and (iii) the control group (4.0%:12/300; 12 heterozygotes). Acquired but not congenital APC resistance (due to the factor V Leiden mutation) is associated with both early and late miscarriage.

G20210A prothrombin gene mutation: prevalence in a recurrent miscarriage population.

Many recurrent pregnancy losses appear to have a thrombotic etiology. We have investigated the prevalence of the G20210A prothrombin gene mutation in 122 women with a history of three or more early (< or = 12 weeks gestation; n = 91), late (> 12 weeks gestation: n = 2), or mixed (n = 29) consecutive pregnancy losses. A control group of 66 healthy parous women with no history of thrombosis or miscarriage was also studied. Four heterozygotes that suffered only early pregnancy losses were detected in the patient group giving a prevalence of 3.3%. Three of the control group women were heterozygous for the mutation. giving a prevalence of 4.5% (p = 0.32: odds ratio 0.71: 95% confidence interval [CI] 0.15-3.27). When only Caucasians were analyzed, a prevalence of 3.9% (4/103) was observed in the patient group and 4.2% (2/48) in the control group (p = 0.28; odds ratio 0.89; 95% CI 0.16-5.05). The prevalence of the G20210A prothrombin gene mutation is not increased in women with recurrent miscarriage, although it was only found in women who had suffered early pregnancy losses. However, it remains possible that this mutation is relevant in a selected subgroup of women with recurrent miscarriage, additional thrombophilic defects, and in whom fetal loss is associated with placental infarction and thrombosis.

Reassortant analysis of guinea pig virulence of pichinde virus variants.

The new world arenavirus Pichinde (PIC) is the basis of an accepted small animal model for human Lassa fever. PIC (Munchique strain) variant P2 is attenuated in guinea pigs, whereas variant P18 is extremely virulent. Previous sequence analysis of the S segments of these two viruses indicated a small number of possible virulence markers in the glycoprotein precursor (GPC) and nucleoprotein (NP) genes. In order to determine the role of these S segment genes in guinea pig virulence in this system, we have generated reassortant viruses. When tested in outbred guinea pigs, the reassortant containing the S segment from the virulent parent P18 (S18L2) caused significantly higher morbidity than the reciprocal reassortant. This increased morbidity was associated with higher viral titers in serum and spleen. However, the S18L2 reassortant was not as fully virulent in this system as the P18 parent, indicating a role for L segment genes in virulence.

Genetic evidence for the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks.

Epizootics of Venezuelan equine encephalitis (VEE) involving subtype IAB viruses occurred sporadically in South, Central and North America from 1938 to 1973. Incompletely inactivated vaccines have long been suspected as a source of the later epizootics. We tested this hypothesis by sequencing the PE2 glycoprotein precursor (1,677 nucleotides) or 26S/nonstructural protein 4 (nsP4) genome regions (4,490 nucleotides) for isolates representing most major outbreaks. Two distinct IAB genotypes were identified: 1) 1940s Peruvian strains and 2) 1938-1973 isolates from South, Central, and North America. Nucleotide sequences of these two genotypes differed by 1.1%, while the latter group showed only 0.6% sequence diversity. Early VEE virus IAB strains that were used for inactivated vaccine preparation had sequences identical to those predicted by phylogenetic analyses to be ancestors of the 1960s-1970s outbreaks. These data support the hypothesis of a vaccine origin for many VEE outbreaks. However, continuous, cryptic circulation of IAB viruses cannot be ruled out as a source of epizootic emergence.

Sequence analysis of the small RNA segment of guinea pig-passaged Pichinde virus variants.

The established animal model for Lassa fever is based on the new world arenavirus Pichinde (PIC). Natural isolates of PIC virus are attenuated in guinea pigs, but serial guinea pig passage renders them extremely virulent in that host. We have compared the nucleotide sequences of the small RNA segments of two attenuated, low-passage variants of the PIC virus Munchique strain (CoAn 4763) and two virulent, high-passage derivatives. Missense mutations in the glycoprotein precursor (GPC) gene at codons GPC-119, GPC-140, and GPC-164 and the nucleoprotein gene (NP) codons NP-35 and NP-374 were most closely associated with virulence. Codon GPC-140 is predicted to represent a region of peak hydrophilicity of the glycoprotein 1 (GP1); it is conceivable that mutations at this site could influence virulence by altering B cell epitopes or virus attachment protein conformation.

The action of heavy metals on the gametes of the marine mussel, Mytilus edulis (L.)--I. Copper-induced uncoupling of respiration in the unfertilized egg.

The direct addition of Cu2+ to unfertilized eggs of Mytilus edulis results in a stimulation of respiration with maximal stimulation occurring at a Cu2+ concentration of ca 0.5 mM. By contrast, the addition of Zn2+ has no effect on egg respiration. The uncoupler CCCP produces a 5/6 fold stimulation of egg respiration but the addition of ADP leads to only a small release of respiration. In contrast, sperm respiration is unaffected by Cu2+, inhibited by Zn2+ and CCCP produces only a small respiratory stimulation. The addition of Cu2+ to respiring Mytilus mantle tissue mitochondria produces an initial stimulation of State 4 oxidation which is then followed by a progressive inhibition. It is suggested that respiration in the unfertilized egg may be inhibited by a high ATP/ADP ratio in the cytosol. Respiration can, therefore, be released by either the addition of a H+-translocating uncoupler or by Cu2+ which may act by stimulating mitochondrial K+ influx.

Dolichylphosphate-dependent Glycosyl Transfer Reactions in the Endoplasmic Reticulum of Castor Bean Endosperm.

In the endosperm of Ricinus communis (castor bean) a number of glycosyl transferases were found to be present during germination. They catalyze the incorporation of mannose from guanosine diphosphate mannose and of N-acetylglucosamine from uridine diphosphate N-acetylglucosamine into a glycolipid fraction, which had all of the properties of dolichylphosphate and pyrophosphate sugars, respectively. The sugar moiety of dolichylphosphate mannose is transferred to a lipid-oligosaccharide, containing more than 6 hexose units. When the membranes are preincubated with nonradioactive guanosine diphosphate mannose and uridine diphosphate N-acetylglucosamine, radioactivity from dolichylphosphate [(14)C]mannose is also transferred to a glycopolymer. In addition, the formation of radioactive glycoproteins from guanosine diphosphate [(14)C]mannose has been demonstrated using a combination of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autofluorography.All of these reactions occur with the highest specific as well as total activity in the endoplasmic reticulum fraction. Whereas a membrane fraction lighter than the endoplasmic reticulum also contains a significant amount of glycosyl transfer activity, the enzymes seem to be present in very low amounts in glyoxysomes and mitochondria. The activities of the various reactions increase severalfold during the first days of germination, i.e. the time of rapid formation of glyoxysomes. The importance of these results in relation to intracellular protein segregation is discussed.

The induction of enzyme activity in the endosperm of germinating castor-bean seeds.

Endosperm extracts were prepared at various times during germination from intact castor-bean seeds and from seeds from which the embryos had been removed. The sterilized seeds were incubated either on solid water agar or on agar containing 0.3 mM-gibberellic acid. 2. Isocitrate lyase and 3-hydroxyacyl-CoA dehydrogenase had very low activities in the mature seeds, but increased 44-fold and 27-fold respectively during germination. In contrast, the extracts of mature seeds had considerable acid and alkaline lipase activity and this only increased two- to three-fold during the incubation period. 3. Incubation of the seeds with gibberellic acid accelerated the rate of appearance of isocitrate lyase and 3-hydroxyacyl-CoA dehydrogenase. It also increased the total activity attained. However, the application of hormone had, in comparison, little effect on the development of lipase activity. 4. The removal of the embryo had little influence on the development of enzyme activity in the endosperm tissue; only with isocitrate lyase was a decrease in activity observed in the absence of the embryo.

The breakdown of lipid reserves in the endosperm of germinating castor beans.

1. Lipid extracts were obtained from castor-bean endosperm tissue at various times during germination and, after purification, the total lipid content was determined. Quantitative measurements of the triglyceride and phospholipid content together with the fatty acid composition were made. 2. The total lipid content of the endosperm rapidly decreased during germination; after 10 days less than 20% of the original weight of lipid remained. In contrast, the phospholipid content (initially less than 0.5% of the total lipid) increased slightly during this time. The fatty acid composition and the relative proportions of the triglyceride species of the total lipid extract remained constant during 10 days of germination. 3. Gibberellic acid (0.3 mM) markedly stimulated the rate of lipid breakdown but did not alter either the fatty acid composition or the relative proportion of triglyceride species. 4. The embryo had little effect on lipid metabolism in the endosperm tissue; only after 6 days of germination were differences observed in the rate of fat utilization in the presence and absence of the embryo.