Locomotor changes in length and EMG activity of feline medial gastrocnemius muscle following paralysis of two synergists

The mechanism of the compensatory increase in electromyographic activity (EMG) of a cat ankle extensor during walking shortly after paralysis of its synergists is not fully understood. It is possible that due to greater ankle flexion in stance in this situation, muscle spindles are stretched to a greater extent and, thus, contribute to the EMG enhancement. However, also changes in force feedback and central drive may play a role. The aim of the present study was to investigate the short-term (1- to 2-week post-op) effects of lateral gastrocnemius (LG) and soleus (SO) denervation on muscle fascicle and muscle–tendon unit (MTU) length changes, as well as EMG activity of the intact medial gastrocnemius (MG) muscle in stance during overground walking on level (0%), downslope (−50%, presumably enhancing stretch of ankle extensors in stance) and upslope (+50%, enhancing load on ankle extensors) surfaces. Fascicle length was measured directly using sonomicrometry, and MTU length was calculated from joint kinematics. For each slope condition, LG-SO denervation resulted in an increase in MTU stretch and peak stretch velocity of the intact MG in early stance. MG muscle fascicle stretch and peak stretch velocity were also higher than before denervation in downslope walking. Denervation significantly decreased the magnitude of MG fascicle shortening and peak shortening velocity during early stance in level and upslope walking. MG EMG magnitude in the swing and stance phases was substantially greater after denervation, with a relatively greater increase during stance of level and upslope walking. These results suggest that the fascicle length patterns of MG muscle are significantly altered when two of its synergists are in a state of paralysis. Further, the compensatory increase in MG EMG is likely mediated by enhanced MG length feedback during downslope walking, enhanced feedback from load-sensitive receptors during upslope walking and enhanced central drive in all walking conditions

A systematic review of intravenous gamma globulin for therapy of acute myocarditis

BACKGROUND: Intravenous gamma globulin (IVGG) is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. METHODS: We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors) to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. RESULTS: Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT) with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10) showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21) versus historic controls (n = 25). Ten case reports and two case series (total n = 21) described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. CONCLUSION: There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG

A three year descriptive study of early onset neonatal sepsis in a refugee population on the Thailand Myanmar border.

BACKGROUND: Each year an estimated four million neonates die, the majority in the first week of life. One of the major causes of death is sepsis. Proving the incidence and aetiology of neonatal sepsis is difficult, particularly in resource poor settings where the majority of the deaths occur. METHODS: We conducted a three year observational study of clinically diagnosed early onset (<7 days of age) neonatal sepsis (EONS) in infants born to mothers following antenatal care at the Shoklo Malaria Research Unit clinic in Maela camp for displaced persons on the Thailand-Myanmar border. Episodes of EONS were identified using a clinical case definition. Conventional and molecular microbiological techniques were employed in order to determine underlying aetiology. RESULTS: From April 2009 until April 2012, 187 infants had clinical signs of EONS, giving an incidence rate of 44.8 per 1000 live births (95% CI 38.7-51.5). One blood culture was positive for Escherichia coli, E. coli was detected in the cerebrospinal fluid specimen in this infant, and in an additional two infants, by PCR. Therefore, the incidence of bacteriologically proven EONS was 0.7 per 1000 live births (95% CI 0.1-2.1). No infants enrolled in study died as a direct result of EONS. CONCLUSION: A low incidence of bacteriologically proven EONS was seen in this study, despite a high incidence of clinically diagnosed EONS. The use of molecular diagnostics and nonspecific markers of infection need to be studied in resource poor settings to improve the diagnosis of EONS and rationalise antibiotic use

Task-Dependent Inhomogeneous Muscle Activities within the Bi-Articular Human Rectus Femoris Muscle

The motor nerve of the bi-articular rectus femoris muscle is generally split from the femoral nerve trunk into two sub-branches just before it reaches the distal and proximal regions of the muscle. In this study, we examined whether the regional difference in muscle activities exists within the human rectus femoris muscle during maximal voluntary isometric contractions of knee extension and hip flexion. Surface electromyographic signals were recorded from the distal, middle, and proximal regions. In addition, twitch responses were evoked by stimulating the femoral nerve with supramaximal intensity. The root mean square value of electromyographic amplitude during each voluntary task was normalized to the maximal compound muscle action potential amplitude (M-wave) for each region. The electromyographic amplitudes were significantly smaller during hip flexion than during knee extension task for all regions. There was no significant difference in the normalized electromyographic amplitude during knee extension among regions within the rectus femoris muscle, whereas those were significantly smaller in the distal than in the middle and proximal regions during hip flexion task. These results indicate that the bi-articular rectus femoris muscle is differentially controlled along the longitudinal direction and that in particular the distal region of the muscle cannot be fully activated during hip flexion

The effects of endogenous and exogenous androgens on cardiovascular disease risk factors and progression

Cardiovascular disease incidence rates have long been known to significantly differ between the two sexes. Estrogens alone fail to explain this phenomenon, bringing an increasing amount of attention to the role of androgens. Contrary to what was initially hypothesized, androgens seem to have an overall cardioprotective effect, especially in men. Recent studies and published data continue to support this notion displaying a consistent inverse correlation with atherosclerosis progression and cardiovascular disease both in regressive and prospective study models. Clinical studies have also revealed what seems to be a differential androgenic effect on various cardiovascular risk factors between men and women. Further insight indicates that in order to avoid confusion it may be also preferable to separately examine the effects of endogenous androgen levels from exogenous testosterone administration, as well as discern the differential results of low to normal and supraphysiological administration doses. This review summarizes old and recent data according to the above distinctions, in an attempt to further our understanding of the role of androgens in cardiovascular disease

Soluble CD44 Interacts with Intermediate Filament Protein Vimentin on Endothelial Cell Surface

CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12–37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells

Measuring health-related quality of life for child maltreatment: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Child maltreatment causes substantial morbidity and mortality in the U.S. Morbidity associated with child maltreatment can reduce health-related quality of life. Accurately measuring the reduction in quality of life associated with child maltreatment is essential to the economic evaluation of educational programs and interventions to reduce the incidence of child maltreatment. The objective of this study was to review the literature for existing approaches and instruments for measuring quality-of-life for child maltreatment outcomes.</p> <p>Methods</p> <p>We reviewed the current literature to identify current approaches to valuing child maltreatment outcomes for economic evaluations. We also reviewed available preference-based generic QOL instruments (EQ-5D, HUI, QWB, SF-6D) for appropriateness in measuring change in quality of life due to child maltreatment.</p> <p>Results</p> <p>We did not identify any studies that directly evaluated quality-of-life in maltreated children. We identified 4 studies that evaluated quality of life for adult survivors of child maltreatment and 8 studies that measured quality-of-life for pediatric injury not related to child maltreatment. No study reported quality-of-life values for children younger than age 3.</p> <p>Currently available preference-based QOL instruments (EQ-5D, HUI, QWB, SF-6D) have been developed primarily for adults with the exception of the Health Utilities Index. These instruments do not include many of the domains identified as being important in capturing changes in quality of life for child maltreatment, such as potential for growth and development or psychological sequelae specific to maltreatment.</p> <p>Conclusion</p> <p>Recommendations for valuing preference-based quality-of-life for child maltreatment will vary by developmental level and type of maltreatment. In the short-term, available multi-attribute utility instruments should be considered in the context of the type of child maltreatment being measured. However, if relevant domains are not included in existing instruments or if valuing health for children less than 6 years of age, direct valuation with a proxy respondent is recommended. The choice of a proxy respondent is not clear in the case of child maltreatment since the parent may not be a suitable proxy. Adult survivors should be considered as appropriate proxies. Longer-term research should focus on identifying the key domains for measuring child health and the development of preference-based quality-of-life instruments that are appropriate for valuing child maltreatment outcomes.</p

Second to fourth digit ratio (2D: 4D) and prostate cancer risk in the Melbourne Collaborative Cohort Study

BACKGROUND : The ratio of the lengths of index and ring fingers (2D : 4D) is a marker of prenatal exposure to sex hormones, with low 2D : 4D being indicative of high prenatal androgen action. Recent studies have reported a strong association between 2D : 4D and risk of prostate cancer. METHODS : A total of 6258 men participating in the Melbourne Collaborative Cohort Study had 2D : 4D assessed. Of these men, we identified 686 incident prostate cancer cases. Hazard ratios (HRs) and confidence intervals (CIs) were estimated for a standard deviation increase in 2D : 4D. RESULTS : No association was observed between 2D : 4D and prostate cancer risk overall (HRs 1.00; 95% CIs, 0.92–1.08 for right, 0.93–1.08 for left). We observed a weak inverse association between 2D : 4D and risk of prostate cancer for age o 60, however 95% CIs included unity for all observed ages. CONCLUSION : Our results are not consistent with an association between 2D : 4D and overall prostate cancer risk, but we cannot exclude a weak inverse association between 2D : 4D and early onset prostate cancer risk

Androgens and male aging: current evidence of safety and efficacy

Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment