Cutoff Points for Grip Strength in Screening for Sarcopenia in Community-Dwelling Older-Adults: A Systematic Review.

BACKGROUND: Currently, different cutoff points for handgrip strength (HGS) have been used to estimate the prevalence of sarcopenia. In addition, the variability of equipment and protocols for this assessment can significantly influence the early detection of this important public health problem. Thus, this review aims to identify the different cutoff points for HGS adopted for older men and women in screening for sarcopenia. OBJECTIVES: this review aims to identify the different cutoff points for HGS adopted for older men and women in screening for sarcopenia. METHODS: In accordance with the PRISMA 2020 recommendations, which included published studies from the last 10 years, from 6 databases, in 3 different languages. RESULTS: 19.730 references were identified, of which 62 were included for the review. All references analyzed used algorithms and definitions of sarcopenia already known in the literature. Of the studies found, 16 chose to develop cutoff values for HGS based on their own population. The variation in cutoff points was evident when compared between gender and regions of the world. CONCLUSION: It has become evident that there is a variability of normative values for HGS in sarcopenia screening. In addition, this systematic review shows the difference in the cutoff points used between the consensuses and those developed for each population.

Gene-environment interaction: a significant diet-dependent obesity locus demonstrated in a congenic segment on mouse chromosome 7.

We have previously reported suggestive evidence for a locus on Chromosome (Chr) 7 that affects adiposity in F2 mice from a CAST/Ei x C57BL/6J intercross fed a high-fat diet. Here we characterize the effect of a high-fat (32.6 Kcal% fat) diet on male and female congenic mice with a C57BL/6J background and a CAST/Ei-derived segment on Chr 7. Adiposity index (AI) and weights of certain fat pads were approximately 50% lower in both male and female congenic mice than in control C57BL/6J mice, and carcass fat content was significantly reduced. The reduction of fat depot weights was not seen, however, in congenic animals fed a low-fat chow diet (12 Kcal% fat). The congenic segment is approximately 25 cM in length, extending from D7Mit213 to D7Mit41, and includes the tub, Ucp2 and Ucp3, genes, all of which are candidate genes for this effect. Some polymorphisms have been found on comparing c-DNA sequences of the Ucp2 gene from C57BL/6J and CAST/Ei mice. These results suggest that one or more genes present in the congenic segment modulate the susceptibility to fat deposition on feeding a high-fat diet. We were unable to show any significant difference between the energy intakes of the congenic and the control C57BL/6J mice on the high-fat diet. Also, measurements of energy expenditure in male mice at 6 weeks of age, during the first 2 weeks of exposure to the high-fat diet, failed to show any differences between control and congenic animals.

Dietary fat, genetic predisposition, and obesity: lessons from animal models.

This review focuses on animal studies that examine the role of dietary fat in obesity. It is evident from animal experiments that the percentage of energy derived from fat in the diet is positively correlated with body fat content. With few exceptions, obesity is induced by high-fat diets in monkeys, dogs, pigs, hamsters, squirrels, rats, and mice. The mechanisms responsible for this correlation between body fat and dietary fat content are not clear. It has been proposed that a high-fat diet produces hyperphagia, which is solely responsible for the increased body fat content. However, several studies in various rodent models showed that increased body fat content still results when the hyperphagia is prevented. This suggests that some metabolic effects of high-fat diets, independent of hyperphagia, may also be contributing to the obesity induced by high-fat diets. It is also clear from animal studies that genetic factors significantly modulate the body's response to diets high in fat-derived energy. In contrast with the animal studies, studies in humans that have examined the relation between dietary fat content and body fat are inconclusive. The limitations of cross-sectional studies, the lack of controlled feeding trials, and the importance of genetic variation in response explain the absence of conclusive evidence. The lessons learned from animal models point to dietary fat as one potentially important component in the etiology of human obesity. Additional comprehensive studies are warranted to determine the role of dietary fat in the etiology of human obesity.

Inherited non-autosomal effects on body fat in F2 mice derived from an AKR/J x SWR/J cross.

In this study we describe the contribution of matrilineal and patrilineal effects on the adiposity, body weight, and on the weights of individual fat pads in F2 male mice derived from an SWR/J x AKR/J cross. AKR/J mice become obese after 12 weeks on a high-fat diet, whereas SWR/J mice remain relatively lean. Here we report that mice with AKR maternal and AKR paternal grandmothers have significantly larger epidydimal and retroperitoneal fat pads than those with SWR maternal and paternal grandmothers. However, grandparental strain had no effect on the overall adiposity (AI) or the weights of the inguinal, subcutaneous or mesenteric fat pads. The strain of the paternal grandparents had a small but significant effect on body weight. These effects can be attributed to in utero effects, imprinting effects, cytoplasmic and/or Y chromosome transmission of factors controlling body fat. We also describe the presence of a quantitative trait locus (QTL) on Chromosome X, close to DXMit174, which is linked to adiposity, body weight, and to the weights of the individual fat depots. However, this QTL is not responsible for the grandparental strain effects described above.

Efficacy of treatment after measurable diabeticlike retinopathy in galactose-fed rats.

PURPOSE: To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. METHODS: Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [GWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion. Capillary images were analyzed by computer morphometry. RESULTS: At 6 months, the GAL rats exhibited statistically significant (P < 0.05) increases over CON rats in mean capillary basement membrane thickness, capillary density, and dilated channels. These parameters tended to increase with time in most groups, and the differences between GAL and age-matched CON rats were maintained at the 18- and 24-month endpoints. Although the microangiopathies were ameliorated by AL-3152 treatment from the onset (PRV), intervention after 6 months of galactosemia with either galactose withdrawal (GWD) or addition of inhibitor (INT) showed amelioration in only some parameters at 18 months and no statistically significant benefit at the 24-month endpoint. CONCLUSIONS: Amelioration of galactose-induced retinal microangiopathies with AL-3152 in the prevention group suggests an efficacious application of aldose reductase inhibitors in treating diabetic retinopathy, provided treatment can begin soon after the onset of diabetes. Intervention after some of the earliest microscopic lesions neither halted progression of the angiopathy nor provided appreciable benefit at the 24-month follow-up.

Sensitivity to dietary obesity linked to a locus on chromosome 15 in a CAST/Ei x C57BL/6J F2 intercross.

Details of a new model of diet-dependent polygenic obesity are presented. CAST/Ei (Mus m. castaneus) mice remain lean after 12 weeks on a high-fat (32 kcal% fat) diet, while C57BL/6J mice become obese. The genes responsible for the obesity segregate in an F2 population derived from an intercross between CAST/Ei and C57BL/6J mice. Quantitative trait analysis, with simple sequence length polymorphisms (SSLPs) at loci previously linked to rodent obesities, identified a quantitative trait locus (QTL) on Chromosome (Chr) 15, accounting for approximately 9% of the variance in adiposity and 14% of the variance in mesenteric depot size. This locus appears to be at the same location as the dietary obesity-3 (Do3) locus controlling body fat content, which was previously identified in an F2 population derived from an SWR/J x AKR/J cross. This is also at the same location as the multigenic obesity-4 (Mob4) locus found in BSB mice, which display spontaneous polygenic obesity. Suggestive linkage also was found at loci close to the single gene mutations Ay on Chr 2 and tub on Chr 7.

The ab initio crystal structure solution of proteins by direct methods. VI. Complete phasing up to derivative resolution.

The procedure described in the papers I-V of this series [Giacovazzo, Siliqi & Ralph (1994). Acta Cryst. A50, 503-505; Giacovazzo, Siliqi & Spagna (1994). Acta Cryst. A50, 609-621; Giacovazzo, Siliqi & Zanotti (1995). Acta Cryst. A51, 177-188; Giacovazzo & Gonzalez Platas (1995). Acta Cryst. A51, 398-404; Giacovazzo, Siliqi & Gonzalez Platas (1995). Acta Cryst. A51, 811-820], aiming at estimating protein phases via a single heavy-atom derivative, has been improved so as to extend phase determination to all the reflections up to derivative resolution. The quality of the resulting electron-density maps is checked for a number of test strutures. Some of the maps are immediately interpretable, and some can be interpreted after some cycles of solvent flattening and/or histogram matching. The correlation with classical SIR techniques is also discussed.

Inhibition of naphthalene cataract in rats by aldose reductase inhibitors.

Naphthalene-induced cataract in rat lenses can be completely prevented by AL01576, an aldose reductase inhibitor (ARI). In an attempt to understand the mechanism of this inhibition, several ARIs were examined to compare their efficacies in preventing naphthalene cataract, using both in vitro and in vivo models. Two classes of ARIs were tested: One group including AL01576, AL04114 (a AL01576 analog) and Sorbinil contained the spirohydantoin group, while Tolrestat contained a carboxylic acid group. Furthermore, to clarify if aldose reductase played a role in naphthalene-induced cataractogenesis in addition to its role in sugar cataract formation, a new dual cataract model was established for ARI evaluations. This was achieved by feeding rats simultaneously with high galactose and naphthalene or incubating rat lenses in culture media containing high galactose and naphthalene dihydrodiol. Under these conditions, both cortical cataract and perinuclear cataract developed in the same lens. It was found that at the same dosage of 10 mg/kg/day, both AL01576 and AL04114 completely prevented all morphological and biochemical changes in the lenses of naphthalene-fed rats. Sorbinil was less efficacious, while Tolrestat was inactive. AL01576 showed a dose-response effect in preventing naphthalene cataract and at 10 mg/kg/day, it was also effective as an intervention agent after cataractogenesis had begun. With the dual cataract model, Tolrestat prevented the high galactose-induced cortical cataract but showed no protection against the naphthalene-induced perinuclear cataract. AL01576, on the other hand, prevented both cataract formations. Results for dulcitol and glutathione levels were in good agreement with the morphological findings. AL04114, and ARI as potent as AL01576 but without its property for cytochrome P-450 inhibition, displayed similar efficacy in preventing naphthalene cataract. Based on these results, it was concluded that the prevention of the naphthalene cataract probably results from inhibition of the conversion of naphthalene dihydrodiol to 1,2-dihydroxynaphthalene and that the effect of the ARIs cannot be explained by their inhibition of the dihydrodiol dehydrogenase activity of aldose reductase.

Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice. AKR/J mice are sensitive to dietary obesity when fed a high fat diet while SWR/J mice are resistant. Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity. Using an F2 mapping population of 931 male mice we found significant linkage with a QTL on chromosome 9 (Likelihood of the Odds [LOD] ratio of 4.85) and another QTL on chromosome 15 (LOD = 3.93). The presence of a QTL on chromosome 15 was confirmed in a separate mapping population of 375 male F1 x SWR/J mice (LOD = 3.82). These two loci are designated dietary obese 2 (Do2) and dietary obese 3 (Do3) for the chromosome 9 and 15 loci, respectively. Both of these chromosomal regions contain candidate genes which may contribute to variation in the phenotype. These loci also exert a significant control over individual adipose depot weights.

Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4.

We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity. AKR/J and SWR/J male mice, as well as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight and energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weight of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examination of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a minimum of one to four genetic loci and that there is significant dominance of the AKR/J genotype. A preliminary analysis with markers linked to the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that maps distal to the db gene on Chromosome (Chr) 4. This locus has been designated dietary obese 1 or Do1.

Comparison of the pharmacokinetics and pharmacodynamics of the aldose reductase inhibitors, AL03152 (RS), AL03802 (R), and AL03803 (S).

The pharmacokinetics of AL03152 (RS) and its enantiomers, AL03802 (R) and AL03803 (S), were studied in the Sprague-Dawley rat following intravenous bolus administration. The enantiomers had differing pharmacokinetic profiles, while the racemic compound exhibited pharmacokinetic parameters approximating the mean values of the individual enantiomers. The total clearance (CLT) values of the two enantiomers were similar, but the intrinsic clearance (Cl(int)) was much greater for the S-enantiomer than for the R-enantiomer. The volume of distribution (Vss) for AL03802 (R) was threefold greater than that for AL03803 (S). The stereoselectivity in Vss could not be totally accounted for by the slight difference in serum protein binding of the isomers and resulted in a difference in the half-lives of the enantiomers. Only the R-isomer exhibited a persistent terminal elimination phase, consistent with more extensive tissue binding than the S-isomer. AL03152 enantiomers were equivalent in potency assessed from in vitro IC50 values toward rat lens aldose reductase and rat kidney L-hexonate dehydrogenase and lens EC50 values in diabetic rats.

Treatment of difficult fractures and nonunions of the humerus and elbow with a modified Küntscher nail.

A series of fourteen difficult fractures and nonunions of the humerus and elbow have been treated over a period of twenty-eight years with a modified Kuntscher Nail. A total of twenty-six operative attempts had been previously made in this group of fourteen patients. One patient had eight failed surgeries prior to treatment. Slots were placed along the spine of the nail for transfixion with screws. In two instances additional modification of the Kuntscher nail was made by attaching a plate to the end of the nail for fixation to the ulna after retrograde insertion into the humerus. One such device was used to fuse the elbow. The other was used to stabilize a low nonunion in which the elbow was already fused. Union was obtained in nine cases with failure in five. Four of the failures united with one additional surgery. The one failed case had a surgical neck fracture which was eventually treated with a Neer prosthesis. The method described may not be superior to other methods; however, it can be successful in obtaining union in difficult elbow and humerus fractures or nonunions resulting from multiple failed prior procedures.

Pharmacokinetics and efficacy of structurally related spirohydantoin and spirosuccinimide aldose reductase inhibitors.

1. Six potent aldose reductase inhibitors (ARI), three spirohydantoin (I to III) and three spirosuccinimide (IV to VI) compounds, showed similar IC50 activities in vitro for the inhibition of rat lens aldose reductase, but their ED50 values in diabetic rats varied as much as 20-fold in the lens and 50-fold in the sciatic nerve tissue. Pharmacokinetic studies were undertaken to investigate these findings. Structure-pharmacokinetic relationships were studied following i.v. administration to cynomolgus monkeys. 2. The clearance (CL) of each spirosuccinimide ARI was faster (greater than 5 times) than that of the corresponding spirohydantoin compound. In both series the CL values of the C(4) methyl and methoxy analogues were 4-fold greater than those for the unsubstituted compounds, although the CL values of the methoxy and methyl derivatives in the same series were not significantly different. 3. The volumes of distribution (Vss) of the spirohydantoins were about one-half those of the corresponding spirosuccinimides, and the Vss values of the parent compounds of both ARI series did not differ dramatically from those of their methyl and methoxy analogues. 4. All six compounds were eliminated from plasma in a biexponential fashion. The half-lives (lambda 1 and lambda 2) of the spirohydantoin compounds were much longer than those of the corresponding spirosuccinimide compounds, and the unsubstituted compounds had longer half-lives than their methyl and methoxy derivatives. The longest lambda 1 and lambda 2 half-lives were observed for imirestat, while two of the spirosuccinimides had the shortest half-lives. 5. These results indicate that the relationships observed between the in vitro and in vivo activities of the six ARI can be attributed to structurally dependent differences in metabolic clearance.

Inhibition of uptake of 1-methyl-4-phenylpyridinium ion and dopamine in striatal synaptosomes by tobacco smoke components.

To determine whether the attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by tobacco smoke exposure is caused by inhibition of the neuronal uptake of 4-phenylpyridinium ion (MPP+), various tobacco components and a smoke extract were tested for inhibitory activity in striatal synaptosomes. A dimethylsulfoxide extract of tobacco smoke filtrate was found to inhibit the uptake of MPP+ and dopamine. These results suggest that inhibition of the neuronal dopamine uptake mechanism may account for the protective effects of smoke exposure on MPTP-induced neurotoxicity.

Reformulation and drop size of apraclonidine hydrochloride.

We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.

A survey of the opinions of obesity experts on the causes and treatment of obesity.

A survey of opinions on the causes and effectiveness of treatment of obesity was carried out on 50 physicians and scientists involved in obesity research. Responses were grouped by region (Europe, North America, and United Kingdom), sex, age (30-50 and greater than 50 y) and degree (MD or PhD). Genetic factors were considered the most important causes of obesity overall. Females viewed lack of physical activity, carbohydrate craving, and weight cycling as significantly more important causes than did their male colleagues and viewed exercise as a more effective treatment. There were regional variations in the assessment of the importance of metabolic defects and weight cycling as causes of obesity and in the usefulness of diet in the treatment of obesity. The older group of respondents rated low-fat diet more highly as a treatment than did their younger colleagues. All groups viewed serotonergic and thermogenic drugs as effective treatments whose usefulness would increase during the next 10 years.

Testing of the durability of single-crystal calcium fluoride with and without antireflection coatings for use with high-power KrF excimer lasers.

The transmission of uncoated and antireflection (AR)-coated CaF(2) windows has been measured during long KrF laser exposures. Samples were tested for up to 75 million pulses in front of an industrial-grade KrF excimer laser at high repetition rates (200-300 Hz) and moderately high energy fluence (220-550 mJ/cm(2)). In this fluence range bare CaF(2) performs much better than the best fused silicas currently available. Various AR coatings (whose structures were initially unknown to us) were deposited on CaF(2) substrates polished to two distinct surface finishes. We determined the coating structures by usingx-ray fluorescence spectroscopy to identify positively all elements that were heavier than fluorine and Rutherford backscattering spectroscopy to determine the layer structure and approximate layer thicknesses. We confirmed the structures by comparing measured UV transmission spectra with computer simulations. This study reveals excellent performance for SiO(2)/Al(2)O(3)/SiO(2)/Al(2)O(3) coatings on highly polished substrates, which provided two-sided transmission in excess of 99.8% at 248 nm and no measurable deterioration after 75 million pulses. AMgF(2)/Al(2)O(3) coating also performed quite well, while a hafnia-containing coating (MgF(2)/HfO(2)/LaF(3)) exhibited anomalous behavior. All-fluoride coatings consisting of MgF(2)/LaF(3)/MgF(2) and MgF(2)/LaF(3)/AlF(3) had good durability but lower starting transmission as a result of scatter losses in the LaF(3) layer. These results demonstrate the availability of AR-coated CaF(2) optics for high-power KrF laser applications with high transmission and no sign of degradation up to ~7 x 10(7) pulses.