The origin of betaine in mouse oocytes and preimplantation embryos†.

Betaine has important roles in preimplantation mouse embryos, including as an organic osmolyte that functions in cell volume regulation in the early preimplantation stages and as a donor to the methyl pool in blastocysts. The origin of betaine in oocytes and embryos was largely unknown. Here, we found that betaine was present from the earliest stage of growing oocytes. Neither growing oocytes nor early preantral follicles could take up betaine, but antral follicles were able to transport betaine and supply the enclosed oocyte. Betaine is synthesized by choline dehydrogenase, and female mice lacking Chdh did not have detectable betaine in their oocytes or early embryos. Supplementing betaine in their drinking water restored betaine in the oocyte only when supplied during the final stages of antral follicle development but not earlier in folliculogenesis. Together with the transport results, this implies that betaine can only be exogenously supplied during the final stages of oocyte growth. Previous work showed that the amount of betaine in the oocyte increases sharply during meiotic maturation due to upregulated activity of choline dehydrogenase within the oocyte. This betaine present in mature eggs was retained after fertilization until the morula stage. There was no apparent role for betaine uptake via the SIT1 (SLC6A20) betaine transporter that is active at the 1- and 2-cell stages. Instead, betaine was apparently retained because its major route of efflux, the volume-sensitive organic osmolyte - anion channel, remained inactive, even though it is expressed and capable of being activated by a cell volume increase.

The Hip-spine Assessment of a Novel Surgical Planning Software Provides Acetabular Component Targets That Are Reliable and in Agreement With Current Clinical Recommendations.

Background: Spinopelvic immobility has been reported to increase dislocation risk following total hip arthroplasty. Surgically placing acetabular components in a functional orientation has been shown to mitigate risk. The aim of this study was to evaluate the validity and reliability of novel surgical planning software to generate clinically recommended cup targets. Methods: Hip-spine assessments were performed retrospectively on 40 patients. Five reviewers, including 3 arthroplasty-trained surgical fellows and 2 clinical research scientists performed the assessments. Hip-spine assessments consisted of measuring anterior pelvic plane tilt, sacral slope, pelvic incidence, and lumbar lordosis on standing anteroposterior pelvis and lateral standing and seated hip-spine images. Generated cup targets and a control group (40°/20° relative to the anterior pelvic plane) were compared to clinically recommended cup targets. Agreement was defined as a cup position within the recommended range or within 3° of a specific target (eg, 40° inclination) when no range was provided. Intraclass correlation coefficients were used to assess interrater and intrarater reliability, and McNemar's chi-square test was used to measure success relative to the control group. Results: The intraclass correlation coefficient was 0.88 for delta sacral slope and 0.92 for pelvic incidence-lumbar lordosis mismatch. For patients with spinopelvic risk factors, the generated targets matched the clinical recommendations in 81% of patients compared to only 16% in the control group. Conclusions: Excellent interrater and intrarater reliability was achieved using the novel surgical planning software. The resultant target values agreed with clinical recommendations to a greater extent than the control group.

Improving alignment in total knee arthroplasty: a cadaveric assessment of a surgical navigation tool with computed tomography imaging.

PURPOSE: To investigate the accuracy of an imageless, optical surgical navigation tool to assist with femoral and tibial bone cuts performed during TKA. PATIENTS AND METHODS: Six board-certified orthopedic surgeons participated in a laboratory cadaver investigation, performing femoral and tibial bone cuts with the assistance of a computer navigation tool. Femoral and tibial varus/valgus, tibial slope, femoral flexion, and both femoral and tibial rotation measurements from the device were compared with angular measurements calculated from computed tomography (CT) images of the knees. RESULTS: Measurements with the navigation tool were highly correlated with those obtained from CT scans in all three axes. For the distal femoral cut, the absolute mean difference in varus/valgus was 0.83° (SD 0.46°, r = 0.76), femoral flexion was 1.91° (SD 1.16°, r = 0.85), and femoral rotation was 1.29° (SD 1.01°, r = 0.88) relative to Whiteside's line and 0.97° (SD 0.56°, r = 0.81) relative to the posterior condylar axis. For the tibia, the absolute mean difference in varus/valgus was 1.08° (SD 0.64°, r = 0.85), posterior slope was 2.78° (SD 1.40°, r = 0.60), and rotation relative to the anteroposterior axis (posterior cruciate ligament to the medial third of the tibial tuberosity) was 2.98° (SD 2.54°, r = 0.79). CONCLUSION: Utilization of an imageless navigation tool may aid surgeons in accurately performing and monitoring femoral and tibial bone cuts, and implant rotation in TKA and thus, more accurately align TKA components.

Performance during reactive handrail grasping during forward walking by young and older adults with and without prior knowledge of the direction of movement is correlated with grip strength.

It has been suggested that the most frequent cause of falls in assisted-living facilities is due to incorrect weight shifting. Lateral instability and weakness have also been linked to falls risk. The objective of this study was to evaluate balance responses to weight shifting during walking and to investigate age-related changes in movement and strength. Thirty-two participants (16 young, 16 older) completed 12 straight walking trials and 6 trials in each condition where a weight shift was required to grasp a handrail. Instructions were to walk down the pathway and, if cued, grasp the handrail as quickly as possible. Conditions included left and right grasping trials, with and without prior knowledge about the movement direction. Kinematic data were recorded and center of mass (COM) was calculated to examine whole body movements. A clinical balance test, strength, and body composition measures were captured to facilitate exploration into the relationship of these measures with reactive movements used during weight transfers. Young adults had quicker lateral COM velocities and reached peak velocity earlier. Males completed the task quicker than females and, for everyone, having knowledge about direction enabled quicker responses. Grip strength was correlated to most performance metrics in this study; more-so than body composition. Slower reactive movements might reflect a more cautious strategy in the older adults or it may highlight changes that occur with increased age and strength changes.

The vestibulomyogenic balance response is elevated following high-intensity lengthening contractions of the lower limb.

The purpose was to investigate whether exercise-induced muscle weakness of the plantar and dorsiflexors through high-intensity lengthening contractions increases the vestibulomyogenic balance response. Nine males (∼25 years) participated in three experimental testing days to evaluate the vestibular control of standing balance and neuromuscular function of the plantar and dorsiflexors pre- and post (30 min, and 1 and 7 days) high-intensity lengthening plantar and dorsiflexions. To evaluate the vestibular-evoked balance response, participants stood quietly on a force plate while exposed to continuous, random electrical vestibular stimulation (EVS) for two 90-s trials. Relationships between EVS-antero-posterior (AP) forces and EVS-medial gastrocnemius electromyography (EMG) were estimated in the frequency domain (i.e., coherence). Weakness of the right plantar and dorsiflexors were assessed using maximal voluntary contraction (MVC) torque. The lengthening contractions induced a 13 and 24% reduction in plantar and dorsiflexor MVC torque, respectively (p < 0.05) of the exercised leg, which did not recover by 1 day post. The EVS-EMG coherence increased over a range of frequencies up to 7 days post compared to pre-lengthening contractions. Conversely, EVS-AP forces coherence exhibited limited changes. The greater EVS-EMG coherence post exercise-induced muscle weakness may be a compensatory mechanism to maintain the whole-body vestibular-evoked balance response when muscle strength is reduced.

Stepping Responses in Young and Older Adults Following a Perturbation to the Support Surface During Gait.

The objective of this work was to investigate the influence perturbation direction has on postural responses during overground gait, and whether these responses are age related. Differences in stepping patterns following perturbations of the support surface were examined in the frontal and sagittal planes during forward walking. Eleven young and 10 older adults completed Mini BESTest, hip strength tests, and 45 perturbed walking trials, triggered on heel contact. Lateral perturbations were more challenging to postural stability for both groups. Step length measures showed young adults recovered in the step proceeding the perturbation, while older adults needed additional steps to regain balance. Young adults arrested center of mass movement by producing larger step widths than older adults following the support surface perturbation.

Comparison of Bioelectrical Impedance Analysis and Air Displacement Plethysmography in Community-Dwelling Older Adults.

Clinicians and researchers use body composition measurements to identify individuals who may be at risk of adverse health complications. This study compared two commonly used two-compartmental anthropometric models (bioelectrical impedance analysis [BIA] and air displacement plethysmography [ADP]) to determine whether these two cost-effective methods would provide similar fat free mass index (FFMI) values in a mixed and sex-separated sample population of healthy older adults. Community-dwelling older adults (N= 37, 18 men) aged 74.5 ± 5.2 years participated. FFMIBIAwas correlated with FFMIADP(r= .916); however, these correlations were markedly reduced when the population was split by sex (r< .60). The level of agreement between the difference values (FFMIBIA- FFMIADP) fluctuated ± 2.1 kg/m(2)(illustrated via Bland-Altman plots), but these differences were not statistically different from 0. Findings from the current work suggest that clinicians must be cautious when using portable devices such as BIA to assess FFMI in an older adult population.

Using electronic surveys to gather information on physician practices during a response to a local epidemic--Rhode Island, 2011.

BACKGROUND: Electronic invitations may improve physician response rates to participate in internet surveys administered by public health agencies. METHODS: Following an increase in reported HIV/syphilis co-infection diagnoses among men-who-have-sex-with-men in Rhode Island, we invited the state's 700 adult primary care and emergency medicine physicians via e-mail to participate in an online, multiple choice survey covering their knowledge, attitudes, and practices regarding sexually transmitted diseases and HIV testing and prevention. Survey invitations were released in three waves over 28 days, triggered by declining daily response rates. RESULTS: Among 53% (n = 372) who agreed to participate, 68% (n = 252) completed all questions. Response was higher among internal medicine physicians than either family medicine or emergency medicine physicians (63% vs. 20% and 19%, respectively; P<0.0001). Daily response rates were highest in the first 48 hours after sending a reminder e-mail. CONCLUSION: This approach supported the Rhode Island Department of Health in rapidly gathering useful physician practice information during an outbreak. Internet-based survey tools coupled with increased prevalence of mobile communication devices and social media could greatly decrease the time and cost of shoe-leather epidemiology.

Predicting fat-free mass index and sarcopenia: a pilot study in community-dwelling older adults.

Age-related muscle loss, termed sarcopenia, has been linked to an increased risk of falls, disability, and mortality. The purpose of this study was to develop a predictive measurement tool to estimate normalized fat-free mass index (FFMI), a means of identifying sarcopenia, in community-dwelling older adults. Functionally relevant measurements including mobility tests, food records, circumference measures, balance, and gait variables were included to ensure this model was comprehensive and accessible to clinicians. Eighty-five community-dwelling older adults (42 male) aged 75.2 ± 5.7 years participated. Each completed two questionnaires regarding general health and physical activity levels. Anthropometric, strength, balance, gait, nutrition, and body composition tests were then conducted. A fat-free mass value, determined by bioelectrical impedance analysis, was normalized by height (FFMI). FFMI along with grip strength and gait speed was used to classify sarcopenia. FFMI was significantly correlated with all circumference measures (waist, arm, calf, and thigh) and body mass index (BMI), but no nutritional parameters. In males, maximum grip strength and a novel quiet balance measure, time outside of a 95% confidence ellipse (TOE), were both positively correlated to FFMI. In females, age and double-support time correlated to FFMI. The prediction equation that accounted for the most variability of FFMI included the independent variables: sex, step time, BMI, and TOE (adjusted R(2) = 0.9272). The proposed linear regression model can successfully predict FFMI values to a high level of accuracy in men and women. With this information, sarcopenia can be predicted by clinicians, and early interventions can be planned and implemented.

Sarcopenia and predictors of the fat free mass index in community-dwelling and assisted-living older men and women.

The purpose of this study was to assess the relationship of the fat free mass index (FFMI), an indicator of sarcopenia in older adults, to anthropometric, gait, balance, and strength measures. We hypothesized that strength, balance, and mobility measures will correlate, and could be used to predict FFMI in older adults. Thirty-three older adults (81.5±7.9 years) participated. Fat free mass (FFM) was measured using Air-Displacement Plethysmography (ADP). Anthropometric measures, maximum handgrip (MG) and quadriceps strength were quantified. Clinical tests included the Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and the Timed-up and Go (TUG) test. Finally, variability measures in gait and balance were calculated. Means, standard deviations (SD), correlations and multiple linear regression statistical analyses were then performed using functional predictor variables for FFMI. In total, 54.5% males and 36.3% females in our population were classified sarcopenic. FFMI correlated only to waist circumference (Total population (Pop), R(2)=0.649 p<0.01; Sarcopenics (Sarc), R(2)=0.636, p<0.05) and maximum grip strength (Pop, R(2)=0.633, p<0.01; Sarc, R(2)=0.771, p<0.01), nullifying our hypothesis. Multiple linear regression analyses revealed waist circumference, maximum handgrip strength, greater variability of time spent in double support, and anterior-posterior balance variability predicted 70.7% of the variance within the population. Results demonstrate a successful predictor model for FFMI based on a combination of strength, circumference and gait/balance variance measures. The ability to predict FFMI based on these variables will facilitate the diagnosis of sarcopenia in older adults.

HIV: inflammation and bone.

HIV infection and antiretroviral therapy (ART) are now established independent risk factors for osteoporosis. With a spate of recent studies reporting significant elevations in fracture prevalence in HIV patients, and a rapidly aging demographic, defining the mechanisms underlying HIV/ART-induced skeletal decline has become imperative. The recent emergence of the field of "osteoimmunology" has provided a conceptual framework to explain how the immune and skeletal systems interact. Furthermore, it is becoming clear that inflammatory states leading to perturbations in the immuno-skeletal interface, a convergence of common cells and cytokine mediators that regulate both immune and skeletal systems, conspire to imbalance bone turnover and induce osteoporosis. In this review we examine the role of inflammation in the bone loss associated with diverse inflammatory conditions and new concepts into how the underlying mechanisms by which inflammation and immune dysregulation impact bone turnover may be pertinent to the mechanisms involved in HIV/ART-induced bone loss.

Tumoral and angiogenesis factors in hepatocellular carcinoma after locoregional therapy.

Locoregional therapy (LRT) is used as a bridge to orthotopic liver transplant (OLT) for hepatocellular carcinoma (HCC) patients. Liver explants in OLT patients with HCC were studied regarding both tumor stage, histology, and immunohistochemical staining for cytokeratin (CK)7, CK19, P53, Ki-67, and vascular endothelial growth factor (VEGF). Patients receiving no LRT (control) (n=30) were compared with LRT treatment groups with conventional transarterial chemoembolization (cTACE) (n=25) or drug-eluting bead transarterial chemoembolization (DEB TACE) (n=17). Tumor stage and histology were similar between treatment and control groups. The mean percent necrosis was significantly higher for treatment groups versus the control group (p<0.0001 for both groups versus control) and was significantly higher in the cTACE group versus the DEB TACE group. Only the DEB TACE group showed peritumoral CK19 positivity, and tumors were all CK19-negative. Using a threshold of 50% of tumoral cells, tumoral VEGF was significantly different between groups, with the control group having the highest degree of positivity; however, peritumoral VEGF was not significantly different between the groups. The Ki-67 proliferation fraction was higher in the treated groups with a statistically significant difference between the DEB-treated group and those without treatment (p=0.02). There were no statistically significant differences in tumoral or peritumoral CK7 or p53. Percent necrosis and percent Ki-67 positivity were higher with LRT, with a significant difference between groups for percent necrosis, confirming that LRT causes necrosis and suggesting that treatment leads to increased proliferation and decreased tumoral VEGF.

Rumination, goal linking, daily hassles and life events in major depression.

BACKGROUND: Rumination in response to stressful events and depressed mood leads to harmful outcomes. In addition to intra-psychic processes, depression is also associated with daily hassles and major life events. Self-regulatory beliefs such as goal linking could mediate the link between life events, daily hassles, rumination and major depression. METHOD: The relationships between depressed mood, rumination, goal linking, life events and daily hassles were investigated in a between-groups design. Standardized questionnaire measures of these constructs were used to compare depressed participants with a group of people experiencing psychological distress, but not major depression, and a never-depressed group. RESULTS: Participants with major depression experienced similar numbers of life events as the other groups, though the impact of these was greater for the depressed group than either the psychological distress group or the healthy controls. Depressed participants also experienced greater daily hassles than either of the other two groups. Depressed participants were also higher in goal linking and rumination. Regression analysis demonstrated that neither life events nor goal linking predict rumination or depressed mood. Rumination appears to moderate the relationship between daily hassles and depressed mood. DISCUSSION: Theoretical and clinical implications are discussed.