Longitudinal study of depressive symptoms and progression of insulin resistance in youth at risk for adult obesity

OBJECTIVE The purpose of this study was to determine whether having childhood depressive symptoms is a risk factor that prospectively predicts impairment in glucose homeostasis. RESEARCH DESIGN AND METHODS A non-treatment-seeking sample of 115 children (aged 5-13 years), oversampled for being at risk for adult obesity, was assessed at baseline and again ~6 years later. Children self-reported depressive symptoms using the Children's Depression Inventory at baseline. Insulin resistance was assessed at baseline and follow-up with the homeostasis model assessment of insulin resistance index (HOMA-IR). RESULTS Children's depressive symptoms were a significant predictor of follow-up HOMA-IR, fasting insulin, and fasting glucose in models accounting for baseline HOMA-IR, insulin, or glucose values; sex; race; baseline age; baseline BMI; change in BMI at follow-up; family history of type 2 diabetes; and time in the study (P < 0.01). CONCLUSIONS In this study, depressive symptomatology at baseline predicted the progression of insulin resistance during child and adolescent development independent of changes in BMI. Research is needed to determine whether early intervention to decrease elevated depressive symptoms in youth ameliorates later development of insulin resistance and lessens the risk of type 2 diabetes.     

A three-dimensional kinematic and kinetic comparison of overground and treadmill walking in healthy elderly subjects

Background

Instrumented treadmills offer a number of advantages for the biomechanical analysis of elderly gait, yet it is unclear how closely treadmill gait approximates overground gait. Although studies have indicated that the kinematics and kinetics of overground and treadmill gait are very similar in young adults, it still needs to be determined whether data collected in elderly adults during treadmill walking can be generalized to overground gait. The purpose of this study, therefore, was to compare the three-dimensional kinematics and kinetics of treadmill gait to overground gait in a group of healthy elderly subjects.

Methods

Three-dimensional kinematic and kinetic data for 18 healthy, nondisabled elderly subjects, age 65–81 years, were collected for speed-matched overground and treadmill walking conditions.

Findings

Overall, the kinematics and kinetics of gait during treadmill and overground walking in the elderly had very similar patterns. However, during treadmill walking elderly subjects showed greater cadence, smaller stride length and stride time as well as reductions in the majority of joint angles, moments and powers when compared to overground walking.

Interpretation

The large increase in cadence suggests that an effective method of acclimation to treadmill walking still needs to be determined. Because of the differences, we believe that in order for instrumented treadmills to become a suitable tool for research and training purposes in healthy elderly, subjects must be adequately acclimated to the treadmill.     

Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells

Cell-based therapy for Duchenne muscular dystrophy patients and mdx mice has proven to be a safe but ineffective form of treatment. Recently, a group of cells called muscle side population (SP) cells have been isolated based on their ability to efflux the DNA-binding dye Hoechst. To understand the potential of skeletal muscle SP cells to serve as precursors for muscle, SP cells from the two mice strains mdx(5cv) and C57BL/6N were isolated, transduced, and transplanted. Under coculture conditions with myogenic cells, some cells within the SP cell population can give rise to early Pax7-positive satellite cells and other later stage myogenic cells. Transduced SP cells were transplanted via the tail vein and were shown to successfully deliver enhanced GFP and human microdystrophin to the skeletal muscle of nonirradiated mdx(5cv) mice, thus demonstrating their ability to travel through the capillaries and enter into damaged muscle. These results demonstrate that i.v. delivery of genes via SP cells is possible and that these SP cells are capable of recapitulating the myogenic lineage. Because this approach shows definitive engraftment by using autologous transplantation of noninjured recipients, our data may have substantial implications for therapy of muscular dystrophy.     

Immune history shapes specificity of pandemic H1N1 influenza antibody responses

Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor–binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor–binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region.Most influenza pandemics occur when a new subtype of virus enters the human population. Once introduced into the human population, influenza viruses typically accumulate mutations in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins, a process called antigenic drift. An H1N1 influenza virus strain caused a pandemic in 2009 (Smith et al., 2009) even though H1N1 viruses have circulated in humans from 1918 to 1957 and then again from 1977 to 2009. The 2009 pandemic H1N1 (pH1N1) strain is antigenically distinct from recently circulating seasonal H1N1 (sH1N1) strains and is more closely related to older sH1N1 strains (Garten et al., 2009; Manicassamy et al., 2010; Skountzou et al., 2010).Sera isolated from influenza-infected ferrets are currently used for surveillance of antigenically drifted influenza strains (Stöhr et al., 2012). Anti-pH1N1 antibody responses elicited in ferrets are focused on the highly variable Sa antigenic site of HA (Chen et al., 2010). Conversely, the majority of monoclonal antibodies derived from humans infected or vaccinated with pH1N1 are directed against conserved regions of the HA stalk and receptor binding domain (Li et al., 2012; O’Donnell et al., 2012; Wrammert et al., 2011). Most of these monoclonal antibodies possess many somatic mutations and bind to sH1N1 viruses efficiently, which is consistent with the idea that these antibody responses were likely originally primed by sH1N1 infection and were later recalled during pH1N1 infection/vaccination (Settembre et al., 2011; Wrammert et al., 2011; Li et al., 2012; O’Donnell et al., 2012; Qiu et al., 2012). Understanding the precise events that promote the development of these cross-reactive antibody repertoires will aid in developing a universal influenza vaccine that targets conserved areas of HA.Here, we compared the specificity of pH1N1 antibody responses elicited in different aged humans. We find that most individuals born between 1983 and 1996 elicit pH1N1 antibody responses that are dominated against an epitope near the HA receptor–binding domain. Most sH1N1 viruses that circulated between 1983 and 1996 share homology with the pH1N1 virus in this region of HA. Antibody responses dominated against this HA epitope were induced after sequential infection of ferrets with a 1991 sH1N1 virus and a pH1N1 virus. Most humans born before 1983 or after 1996 did not mount anti-pH1N1 antibody responses against this HA region. Importantly, most sH1N1 viruses that circulated before 1983 or after 1996 have an amino acid mutation or deletion in this HA epitope.     

Mechanical Pain Sensitivity and the Severity of Chronic Neck Pain and Disability Are Not Modulated Across the Menstrual Cycle

Despite the high prevalence of neck pain among women, menstrual effects on regional pain outcomes have not been investigated in this clinical population. This study evaluated menstrual effects on mechanical pain sensitivity (pressure pain threshold [PPT]), neck pain intensity (numeric pain rating scale [NPRS]), and neck-related disability (Neck Disability Index [NDI]) in 22 normally menstruating (NM) and 17 hormonal contraceptive users with chronic neck pain. Sex hormones, PPT, and NDI were measured during the early follicular (F1), late follicular (F2), and luteal (L) menstrual phases. Daily NPRS scores were recorded in an online symptom diary and averaged within each phase. Estradiol and progesterone increased only for NM women in F2 and L, respectively. Phase effects on PPT (η² = .003), NDI (η² = .003), and NPRS (η² = .016) for NM women were small and did not differ from those for the hormonal contraceptive users (P ≥ .386). Averaged across the menstrual cycle, PPT scores explained 29% of the variance in NPRS scores for NM women but were not associated with NDI scores in either group. Results indicate that the magnitude of menstrual effects on mechanical pain sensitivity and the severity of neck pain and disability do not exceed thresholds of clinically detectable change in women with chronic neck pain.     

Subclinical endophthalmitis following a rooster attack

Ocular injury resulting from rooster attacks is rarely reported in the literature. Sadly, the target of these attacks is most often children younger than 3 years old, whose naiveté of the aggressive, territorial behavior of birds can place them at risk. Acute sequelae of these attacks can result in a lifetime of visual impairment. The possibility of a subacute or occult infection is an unusual occurrence that must always be considered. In an effort to prevent future attacks and ocular casualties, we present a case of a 12-month-old boy who suffered an open globe following a rooster attack. The open globe was emergently repaired. One week later, a white cataract was noticed on examination in the absence of systemic or ocular signs of inflammation. Traumatic endophthalmitis and lenticular abscess were suspected during examination under anesthesia. Vitrectomy, lensectomy, and injection of intravitreal antibiotics were performed. Culture of lenticular and vitreous aspirates grew alpha-streptococcus. Alpha-streptococcal endophthalmitis can result from ocular injuries caused by rooster pecking. The infection may present insidiously and without typical ocular or systemic symptoms or signs. Management is challenging and may require surgery.     

Biaxial flexure testing of calcium phosphate bioceramics for use in tissue engineering

This study analyzes data from 206 CaP specimens (68 HA, 70 BCP, and 68 beta-TCP) fractured via biaxial flexure testing. Specimens were divided into four groups: (a) Group I, dry; (b) Group II, wet (day 0, immersion time approximately 5-10 s); (c) Group III, after immersion in media for 21 days (day 21); and (d) Group IV, after culturing osteoblasts (OBs) on the surface for 21 days (day 21 with cells). X-ray diffraction verified the presence of minor second phases in HA and beta-TCP while BCP was a biphasic mixture of HA and beta-TCP with minor phases present. The statistical significance (p < 0.05) of differences in the measured biaxial flexure fracture strength, S, between groups was assessed via one-way ANOVA with Tukey's test. Also, a two-parameter Weibull analysis assessed the mechanical reliability of each group. Osteoblasts increase the biaxial flexure fracture strength in a statistically significant way compared to both the HA discs in Groups II and III. Scanning electron microscope examination revealed grain boundary grooving on the sintered surfaces and with thermal expansion anisotropy, likely leads to the observed rapid strength decline upon exposure to media found in Groups II, III and IV.