Caloric restriction in humans reveals immunometabolic regulators of health span.

The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.

The diagnostic value of phase angle, an integrative bioelectrical marker, for identifying individuals with dysmobility syndrome: the Korean Urban-Rural Elderly study.

Low phase angle, a non-invasive bioimpedance marker, is associated with elevated odds of dysmobility syndrome and its components. Phase angle (estimated cutoffs: < 4.8° in men; < 4.5° in women) can be used to detect dysmobility syndrome in community-dwelling older adults as a simple, integrative screening tool. INTRODUCTION: Dysmobility syndrome uses a score-based approach to predict fracture risk that incorporates the concepts of osteoporosis, sarcopenia, and obesity. Low phase angle (PhA), a simple, non-invasive bioelectrical impedance marker, was associated with low lean mass, high fat mass, and poor muscle function. We aimed to investigate the association between PhA and dysmobility syndrome, with the exploration of the diagnostic cutoffs. METHODS: In a community-dwelling Korean older adult cohort, dysmobility syndrome was defined as the presence of ≥ 3 of the following components: osteoporosis, low lean mass, falls in the preceding year, low grip strength, high fat mass, and poor timed up and go performance. RESULTS: Among the 1825 participants (mean age 71.6, women 66.7%), subjects were classified into sex-stratified PhA tertiles. The prevalence of dysmobility syndrome increased from the highest PhA tertile group to the lowest (15.50 to 2.45% in men; 33.41 to 12.25% in women, P for trend < 0.001). The mean PhA values decreased as the dysmobility score increased (5.33° to 4.65° in men; 4.76° to 4.39° in women, P for trend < 0.001). Low PhA (cutoff: < 4.8° in men; < 4.5° in women) was associated with twofold elevated odds of dysmobility syndrome after adjusting for age, sex, and conventional risk factors. Low PhA improved the identification of individuals with dysmobility syndrome when added to the conventional risk model (area under the curve, 0.73 to 0.75, P = 0.002). CONCLUSION: Low PhA was associated with dysmobility syndrome and its components, independent of age, sex, body mass index, nutritional status, and inflammation.

The expression of vascular endothelial growth factor and Syndecan-4 in cartilage from osteoarthritic knees.

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren-Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis.

BACKGROUND: Vitiligo may develop following minor physical trauma. However, in autologous epidermal grafting, depigmentation of the donor (normally pigmented) site from a suction blister is rare, even in cases displaying failure of repigmentation at the recipient (depigmented) site. OBJECTIVES: To examine whether the suction procedure is more likely to damage keratinocytes in the depigmented than in the normally pigmented epidermis of vitiligo, and to determine what kind of damage occurs to the keratinocytes. METHODS: Paired roofs of suction blisters from five patients with generalized vitiligo, five with localized and seven with segmental type, were used for the study. Multiple new lesions developed in two of the five patients with the generalized type. Apoptosis of keratinocytes in the epidermis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labelling (TUNEL) staining, with immunohistochemistry for Bax and active caspase 3. Expression of Bcl-2, Bax, FLIP and p53, activation of caspases 3, 8 and 9, and cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) in the epidermis were analysed by Western blotting in four patients with each type. RESULTS: Apoptotic keratinocytes, which stained with TUNEL and anti-Bax and antiactive caspase 3 antibodies, were scattered in the blistered epidermis, mainly in the lower portions. The depigmented epidermis displayed significantly more apoptotic keratinocytes than the normally pigmented epidermis. The numerical difference between the paired epidermides was related to the disease activity and not to the type of lesions. The number of apoptotic keratinocytes in the normally pigmented epidermis was as high as that in the depigmented epidermis in the two patients with active generalized type vitiligo. Expression of Bax and p53 in the depigmented epidermis was higher than in the normally pigmented epidermis, whereas expression of FLIP was lower. In addition, the activation of caspases 3, 8 and 9, and cleavage of PARP, were increased in the depigmented compared with the normally pigmented epidermis. The degree of difference in expression and activation was parallel to the results of the TUNEL assay. CONCLUSIONS: The keratinocytes in the depigmented compared with the normally pigmented epidermis of vitiligo may become apoptotic more easily after suction.

Racial/ethnic group differences in the prevalence of sexually transmitted diseases in the United States: a network explanation.

BACKGROUND: Many studies have observed that African Americans have comparatively high rates of selected STDs, often 10 to 20 times higher than whites and other racial/ethnic groups, but without convincing explanation. GOAL: This study attempts to solve this puzzle using data from a nationally representative probability sample and a network approach. STUDY DESIGN: The National Health and Social Life Survey (NHSLS) is a nationally representative probability sample of 1,511 men and 1,921 women in the United States. Logistic regression analysis of these data permit a multivariate analysis of the individual risk factors associated with STDs. Using loglinear analysis and a simulation, we also identify the effects of sexual network patterns within and between racial/ethnic groups. RESULTS: Logistic regression analysis of the NHSLS revealed, even after controlling for all the appropriate individual-level risk factors, that African Americans are almost five times more likely to be infected by bacterial diseases than the other racial/ethnic groups. CONCLUSIONS: African Americans' higher infection rate for bacterial diseases can be explained by the patterns of sexual networks within and between different racial/ethnic groups. First, infections are more widespread in the African American population at large because partner choice is more highly dissortative--meaning that "peripheral" African Americans (who have had only one partner in the past year) are five times more likely to choose "core' African Americans (who have had four or more partners in the past year) than "peripheral" whites are to choose "core" whites. Secondly, sexually transmitted infections stay within the African American population because their partner choices are more segregated (assortative mating) than other groups. The likelihood of African Americans having a sexually transmitted infection is 1.3 times greater than it is for whites because of this factor alone.

Three dimensional shape reconstruction and finite element analysis of femur before and after the cementless type of total hip replacement.

Computerized tomography was used to reconstruct a shape, and stresses in three-dimensional objects were analysed. The human femur, which has a very irregular shape, was chosen as an object. CT image data of a cadaver femur were transferred to a computer, and an edge extraction program generated the cross-section of bone by specifying a range of CT values for each slice. Pixel data from the CT scan are converted into a vector of points (x, y, z) which can specify the boundaries of bone. Lateral surfaces are defined by stacking up the slices and making use of the vectorized data. Intermediate and oblique cross-sections can be obtained by an interpolation technique. The constructed model was used as input data for the finite element analysis. To understand the stress distributions before and after the cementless type of total hip replacement, a three-dimensional finite element stress analysis of the bone-implant system was carried out, assuming micromotions between the stem and the femur. The analysis was done for both frictionless and friction cases, modelling the contact point with a gap element having isotropic friction. The analysis shows that the stress is not concentrated on the femoral calcar when the friction coefficient is large.

Structural stiffness of the Hoffmann simple anterior tibial external fixation frame.

Tibial external fixation frames were constructed on aluminum tube simulating tibia bone. A 20-mm gap was left at the fracture site in order to measure the structural stiffness of the frame rather than the aluminum tube. The performance of the frames were experimentally evaluated and quantified using tests which simulated the loading conditions encountered in normal walking. These included axial compression, anteroposterior (AP) bending, lateral bending and torsional loading of the frame. The parameters studied were (a) number of fixation pins, (b) number of connecting rods and (c) location of clamps on the pins. Four constants were evaluated from these tests using various structural configurations of the frames; these resulted in four stiffness coefficients in compression, AP bending, lateral bending and torsion. Stiffnesses of various frames with different geometric configurations were compared by comparing their appropriate stiffness coefficients. Such comparison can set forth a quantitative guideline in selecting a suitable frame configuration for the type of injury and condition of fracture pattern. This type of quantitative analysis can also be useful in modifying the frame during the postoperative bone healing process.

Tendon excursion of wrist movers.

In mechanical terms, the wrist joint is moved by a system of effective pulleys and levers influenced by the anatomic structures present at the wrist. Assuming that the tendon excursion in a cadaver would reflect the excursion of the corresponding tendon in a live hand moving the wrist through the same arc of motion, this study measures the excursions of the wrist tendons during flexion-extension motion and radioulnar deviation in different positions of forearm rotation and relates tendon function to anatomic configuration. Two separate experiments were performed to measure the tendon excursion, in one of which the data were collected manually and in the other a system of computer-aided data collection was used.

Design of a total wrist prosthesis.

Diseased wrist joints, in such cases as rheumatoid arthritis, are often required to be replaced by a prosthesis to relieve pain and to recover the wrist function. In designing this replacement, it is essential to understand the behavior of a normal wrist joint in its kinematic and kinetic aspects. An experimental and analytical study was conducted to obtain various parameters regarding the normal wrist joint. The significance of these parameters were discussed and are to be used for the design criteria. Based on normal wrist joint study, a universal, constrained, total replacement was designed and compared with the existing prosthesis in a laboratory experiment.

Biomechanical evaluation of metacarpophalangeal joint prosthesis designs.

A laboratory biomechanical analysis of metacarpophalangeal joint prosthesis designs was done with fresh cadaver finger rays. The center of rotation, range of motion, tendon excursion, and fingertip force were determined on the specimens before and after implanting Swanson, Niebauer, Steffee II, St. Georg-Buchholz, Schultz, and modified Strickland prostheses. Their biomechanical behavior varied considerably and none duplicated the normal metacarpophalangeal (MP) joint. Each has design characteristics that may be clinically advantageous as well as disadvantageous. Irrespective of the design, the studies done cannot be divorced from the following factors: (1) implant material properties--silicone rubber implants buckled with tendon loading; this deformity created a significant flexor mechanical advantage and an extensor mechanical disadvantage; (2) implant fixation--freely movable implant stems dampened part of the applied load; braided suture provided inadequate immediate fixation; (3) implantation technique--the articulated prostheses can be technically unforgiving; errors in technique resulted in alteration of their biomechanical behavior.

Kinematics of the wrist. II. Clinical applications.

A reproducible method of measuring carpal height and carpal-ulnar distance and expressing them as ratios of these distances to the length of the third metacarpal, as reported in a previous paper9, was applied to serial roentgenograms of seventeen patients with rheumatoid disease and six patients with Kienböck's disease. These ratios provide an accurate expression of the extent of carpal collapse and of ulnar translation. However, once carpal collapse has occurred, the trajectory of hand motion becomes flattened, and, as a result, the carpal height ratio will vary as the wrist moves from maximum radial to maximum ulnar deviation. These ratios may be of use in predicting a patient's clinical course, but a larger clinical study is necessary before use of the measurements for this purpose can be recommended with assurance.

Clinical and experimental studies on the effect of extensor carpi radialis longus transfer in the rheumatoid hand.

Digital ulnar drift in the rheumatoid hand is a complex problem. The radial deformity of the wrist causes abnormal forces on the extrinsic flexor and extensor tendons which aggravate metacarpophalangeal ulnar drift. Analysis of the results of the transfer of the extensor carpi radialis longus to the extensor carpi ulnaris in 20 wrists showed that 13 of 20 had significant correction of the wrist deformity. The transferred tendon did not contract during active ulnar deviation. Laboratory studies of the transfer on cadaveric rheumatoid wrist models showed correction of the wrist deformity. The dorsal ulnar capsule was determined to be a stabilizer of wrist position, as evidenced by deformity after transection.

An accurate data collection method for spatial motion using a sonic digitizer.

An accurate collecting method for spatial displacement data utilizing a sonic digitizer which works electronically and acoustically is described. The sequence of the operation of the digitizer system is explained. As an application, the study of elbow flexion-extension is presented. Finally, operational precautions for using this system are discussed.

Kinematics of the wrist. I. An experimental study of radial-ulnar deviation and flexion-extension.

The kinematics of the wrist during radial-ulnar deviation and flexion-extension were studied in several ways. In six fresh cadaver wrists, the forearm was fixed in full pronation, each motion was constrained to one plane, and two metal markers were placed in each of the finger metacarpals, as well as in the radius and all of the carpal bones except the pisiform and greater multangular. Radial ulnar and flexion-extension movements in these wrists were studied roentgenographically. In the wrists of six normal volunteers, a similar roentgenographic analysis was carried out and the trajectories of wrist motions also were studied using light-emitting diodes. Finally, roentgenographic measurements were made on 100 wrists of normal subjects. From these studies, it was concluded that: (1) during each of these motions, rotation occurs about a fixed axis located within the head of the capitate, and the location of each axis is not changed by the position of the hand in either plane; (2) the distance from the base of the third metacarpal to the distal articular surface of the radius (the carpal height), measured along the proximally projected axis of the third metacarpal on posteroanterior roentgenograms, is constant throughout radial-ulnar deviation of the normal wrist and can be used as a measure of carpal collapse; and (3) the perpendicular distance of the fixed axis of rotation for radial-ulnar deviation from the distally projected longitudinal axis of the ulna can be used as a quantitative measurement of the amount of translation of the carpus in pathological conditions.

Instantaneous center of rotation by least square method.

In the design of the total replacement of the human joint, the joint center of rotation is often important. This paper describes an analytical technique to study joint kinematics, especially the instantaneous center of rotation. The empirical data for the analysis were obtained by the sonic digitizer system which works acoustically and electronically. As biomechanical applications of the technique, the elbow, the metacarpophalangeal, and wrist joints were studied.