Central defect type partial ACL injury model on goat knees: the effect of infrapatellar fat pad excision

BACKGROUND: The mid-substance central defect injury has been used to investigate the primary healing capacity of the anterior cruciate ligament (ACL) in a goat model. The sagittal plane stability on this model has not been confirmed, and possible effects of fat pad excision on healing have not been evaluated. We hypothesize that excising the fat pad tissue results in poorer ligament healing as assessed histologically and decreased tensile strength of the healing ligament. We further hypothesize that the creation of a central defect does not affect sagittal plane knee stability. METHODS: A mid-substance central defect was created with a 4-mm arthroscopic punch in the ACLs of right knees of all the subjects through a medial mini-arthrotomy. Goats were assigned to groups based on whether the fat pad was preserved (group 1, n = 5) or excised completely (group 2, n = 5). The left knees served as controls in each goat. Histopathology of the defect area along with measurement of type I collagen in one goat from each group were performed at 10th week postoperatively. The remaining knees were evaluated biomechanically at the 12th week, by measuring anterior tibial translation (ATT) of the knee joints at 90° of flexion and testing tensile properties (ultimate tensile load (UTL), ultimate elongation (UE), stiffness (S), failure mode (FM)) of the femur-ACL-tibia complex. RESULTS AND DISCUSSION: Histopathology analysis revealed that the central defect area was fully filled macroscopically and microscopically. However, myxoid degeneration and fibrosis were observed in group 2 and increased collagen type I content was noted in group 2. There were no significant differences within and between groups in terms of ATT values (p = 0.715 and p = 0.149, respectively). There were no significance between or within groups in terms of ultimate tensile load and ultimate elongation; however, group 2 demonstrated greater stiffness than group 1 that was correlated with the fibrotic changes detected microscopically (p = 0.043). CONCLUSIONS: The central defect type injury model was confirmed to be biomechanically stable in a goat model. Resection of the fat pad was noted to negatively affect defect healing and increase ligament stiffness in the central defect injury model

Service use of older people who participate in primary care health promotion: a latent class analysis

Background: Recruiting patients to health promotion programmes who will benefit is crucial to success. A key policy driver for health promotion in older people is to reduce health and social care use. Our aim was to describe service use among older people taking part in the Multi-dimensional Risk Appraisal for Older people primary care health promotion programme. Methods: A random sample of 1 in 3 older people (≥65 years old) was invited to participate in the Multi-dimensional Risk Appraisal for Older people project across five general practices in London and Hertfordshire. Data collected included socio-demographic characteristics, well-being and functional ability, lifestyle factors and service use. Latent class analysis (LCA) was used to identify groups based on use of the following: secondary health care, primary health care, community health care, paid care, unpaid care, leisure and local authority resources. Differences in group characteristics were assessed using univariate logistic regression, weighted by probability of class assignation and clustered by GP practice. Results: Response rate was 34% (526/1550) with 447 participants presenting sufficient data for analysis. LCA using three groups gave the most meaningful interpretation and best model fit. About a third (active well) were fit and active with low service use. Just under a third (high NHS users) had high impairments with high primary, secondary and community health care contact, but low non-health services use. Just over a third (community service users) with high impairments used community health and other services without much hospital use. Conclusion: Older people taking part in the Multi-dimensional Risk Appraisal for Older people primary care health promotion can be described as three groups: active well, high NHS users, and community service users

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin

Can weight loss prevent cancer?

We review and update evidence on obesity, weight gain and weight loss in relation to leading cancers since the International Agency for Research on Cancer report of 2002. Emphasis is placed on the time course of disease and implications for weight control to prevent cancer. We conclude that weight loss could prevent a major portion of common cancers

The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression

BACKGROUND: The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val(158)Met polymorphism. METHOD: In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. RESULTS: We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val(158)met (rs165688; Val allele) rs737865 (G allele) and rs165599 (G allele) all showed reduced expression (P < 0.05). Finally, we observe a strong sexual dimorphism in COMT expression, with females exhibiting significantly greater levels of COMT mRNA. CONCLUSION: The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene

Trends in Mortality from Septicaemia and Pneumonia with Economic Development: An Age-Period-Cohort Analysis

<div><h3>Background</h3><p>Hong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong’s unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching “first world” status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic transition affects infection-related mortality.</p> <h3>Methods</h3><p>We used deaths from septicemia and pneumonia not specified as bacterial, and population figures in Hong Kong from 1976–2005. We fitted age-period-cohort models to decompose septicemia and non-bacterial pneumonia mortality rates into age, period and cohort effects.</p> <h3>Results</h3><p>Septicaemia-related deaths increased exponentially with age, with a downturn by period. The birth cohort curves had downward inflections in both sexes in the 1940s, with a steeper deceleration for women. Non-bacterial pneumonia-related deaths also increased exponentially with age, but the birth cohort patterns showed no downturns for those born in the 1940s.</p> <h3>Conclusion</h3><p>The observed changes appeared to suggest that better early life conditions may enable better development of adaptive immunity, thus enhancing immunity against bacterial infections, with greater benefits for women than men. Given the interaction between the immune system and the gonadotropic axis, these observations are compatible with the hypothesis that upregulation of the gonadotropic axis underlies some of the changes in disease patterns with economic development.</p> </div

No effect of 24 h severe energy restriction on appetite regulation and ad libitum energy intake in overweight and obese males

Background/Objectives: Long-term success of weight loss diets might depend on how the appetite regulatory system responds to energy restriction (ER). This study determined the effect of 24 h severe ER on subjective and hormonal appetite regulation, subsequent ad libitum energy intake and metabolism. Subjects/Methods: In randomised order, eight overweight or obese males consumed a 24 h diet containing either 100% (12105 (1174 kJ; energy balance; EB) or 25% (3039 (295) kJ; ER) of estimated daily energy requirements (EER). An individualised standard breakfast containing 25% of EER (3216 (341) kJ) was consumed the following morning and resting energy expenditure, substrate utilisation and plasma concentrations of acylated ghrelin, glucagon-like peptide-1 (GLP-17–36), glucose-dependant insulinotropic peptide (GIP1–42), glucose, insulin and non-esterified fatty acid (NEFA) were determined for 4 h after breakfast. Ad libitum energy intake was assessed in the laboratory on day 2 and via food records on day 3. Subjective appetite was assessed throughout. Results: Energy intake was not different between trials for day 2 (EB: 14946 (1272) kJ; ER: 15251 (2114) kJ; P=0.623), day 3 (EB: 10580 (2457) kJ; 10812 (4357) kJ; P=0.832) or day 2 and 3 combined (P=0.693). Subjective appetite was increased during ER on day 1 (P0.381). Acylated ghrelin, GLP-17–36 and insulin were not different between trials (P>0.104). Post-breakfast area under the curve (AUC) for NEFA (P<0.05) and GIP1–42 (P<0.01) were greater during ER compared with EB. Fat oxidation was greater (P<0.01) and carbohydrate oxidation was lower (P<0.01) during ER, but energy expenditure was not different between trials (P=0.158). Conclusions: These results suggest that 24 h severe ER does not affect appetite regulation or energy intake in the subsequent 48 h. This style of dieting may be conducive to maintenance of a negative EB by limiting compensatory eating behaviour, and therefore may assist with weight loss

Composition and Function of Haemolymphatic Tissues in the European Common Shrew

BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding

Physical fitness in morbidly obese patients: effect of gastric bypass surgery and exercise training

Background There is a growing consensus that bariatric surgery is currently the most efficacious and long-term treatment for clinically severe obesity. However, it remains to be determined whether poor physical fitness, an important characteristic of these patients, improves as well. The purpose of this pilot study is to investigate the effect of gastric bypass surgery on physical fitness and to determine if an exercise program in the first 4 months is beneficial. Methods Fifteen morbidly obese patients (BMI 43.0 kg/m(2)) were tested before and 4 months after gastric bypass surgery. Eight of them followed a combined endurance and strength training program. Before and after 4 months the operation, anthropometrical characteristics were measured, and an extensive assessment of physical fitness (strength, aerobic, and functional capacity) was performed. Results Large-scale weight loss through gastric bypass surgery results in a decrease in dynamic and static muscle strength and no improvement of aerobic capacity. In contrast, an intensive exercise program could prevent the decrease and even induced an increase in strength of most muscle groups. Together with an improvement in aerobic capacity, functional capacity increased significantly. Both groups evolved equally with regard to body composition (decrease in fat mass and fat-free mass). Conclusions An exercise training program in the first 4 months after bariatric surgery is effective and should be promoted, considering the fact that physical fitness does not improve by weight loss only

Transcriptome characterization and polymorphism detection between subspecies of big sagebrush (Artemisia tridentata)

<p>Abstract</p> <p>Background</p> <p>Big sagebrush (<it>Artemisia tridentata</it>) is one of the most widely distributed and ecologically important shrub species in western North America. This species serves as a critical habitat and food resource for many animals and invertebrates. Habitat loss due to a combination of disturbances followed by establishment of invasive plant species is a serious threat to big sagebrush ecosystem sustainability. Lack of genomic data has limited our understanding of the evolutionary history and ecological adaptation in this species. Here, we report on the sequencing of expressed sequence tags (ESTs) and detection of single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers in subspecies of big sagebrush.</p> <p>Results</p> <p>cDNA of <it>A. tridentata </it>sspp. <it>tridentata </it>and <it>vaseyana </it>were normalized and sequenced using the 454 GS FLX Titanium pyrosequencing technology. Assembly of the reads resulted in 20,357 contig consensus sequences in ssp. <it>tridentata </it>and 20,250 contigs in ssp. <it>vaseyana</it>. A BLASTx search against the non-redundant (NR) protein database using 29,541 consensus sequences obtained from a combined assembly resulted in 21,436 sequences with significant blast alignments (≤ 1e^-15). A total of 20,952 SNPs and 119 polymorphic SSRs were detected between the two subspecies. SNPs were validated through various methods including sequence capture. Validation of SNPs in different individuals uncovered a high level of nucleotide variation in EST sequences. EST sequences of a third, tetraploid subspecies (ssp. <it>wyomingensis</it>) obtained by Illumina sequencing were mapped to the consensus sequences of the combined 454 EST assembly. Approximately one-third of the SNPs between sspp. <it>tridentata </it>and <it>vaseyana </it>identified in the combined assembly were also polymorphic within the two geographically distant ssp. <it>wyomingensis </it>samples.</p> <p>Conclusion</p> <p>We have produced a large EST dataset for <it>Artemisia tridentata</it>, which contains a large sample of the big sagebrush leaf transcriptome. SNP mapping among the three subspecies suggest the origin of ssp. <it>wyomingensis </it>via mixed ancestry. A large number of SNP and SSR markers provide the foundation for future research to address questions in big sagebrush evolution, ecological genetics, and conservation using genomic approaches.</p