Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1-3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5-7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11-13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14-16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18-20.

The evaluation of tactile dysfunction in the hand in type 1 diabetes: a novel method based on haptics.

AIMS: We present an innovative method based on haptics for the evaluation of the sense of touch in the hand, in people affected by type 1 diabetes. METHODS: Forty individuals affected by diabetes and 20 healthy controls took part in the study; the diabetes group was further divided into two subgroups based on vibration sensitivity in the lower limb. By means of a novel haptic device, tactile sensitivity in the fingertip was measured as the ability of the participants to discriminate slip motion speed. RESULTS: Tactile sensitivity was significantly lower in individuals affected by diabetes as compared to controls. Depending on the subgroup, the difference from the controls was equal to 0.11 (95% CI from 0.029 to 0.186) and to 0.267 (95% CI from 0.198 to 0.336). Within the diabetes group, tactile sensitivity correlated with vibration sensitivity in the upper (p = 0.001) and lower limb (p = 0.003). A significant relationship between nerve conduction parameters and tactile sensitivity was found (p = 0.03). Finally, we combined the different predictors (clinical, vibratory and electroneurography data) by using cluster analysis; tactile sensitivity was found to be significantly different between different clusters (p = 0.004). CONCLUSIONS: Early signs of tactile dysfunction in the hand were found in individuals affected by diabetes, even in absence of diabetic neuropathy. The protocol presented in this study is a promising tool for the assessment of tactile dysfunction in the hand in people affected by type 1 diabetes.

Exacerbation of warfarin-induced anticoagulation by hyperthyroidism.

OBJECTIVE: To alert clinicians to the potential interaction between warfarin and hyperthyroidism. METHODS: We present two case reports and compare findings with those in a control population of patients with hyperthyroidism who were not receiving anticoagulant therapy. RESULTS: In two patients, severe coagulopathy was precipitated by the interaction of warfarin and increased thyroid hormone levels. In both cases, the patients also demonstrated resistance to vitamin K therapy, which persisted for several days. We also studied five control patients with hyperthyroidism who were not taking anticoagulant drugs; no effect of thyroid hormone on the plasma levels of vitamin K-dependent clotting factors was noted. One of our patients with hyperthyroidism who was taking warfarin had levels of warfarin in the serum that were 5 times the therapeutic range; this finding suggests that the protein binding or absorption of warfarin may be altered in such patients. CONCLUSION: Multiple factors may contribute to the enhanced effect of warfarin seen in patients with hyperthyroidism, including altered metabolism of vitamin K-dependent clotting factors, altered metabolism of warfarin, or decreased protein binding of the drug. Patients with hyperthyroidism should be given lower doses of warfarin to avoid severe coagulopathy.

Serological surveillance of plague in dogs and cats, California, 1979-1991.

Following natural infection both cats and dogs develop antibodies to plague which can be measured for several months after infection. Besides being helpful in the diagnosis of plague in domestic carnivores, the antibody titer has important implications in outbreak investigation and surveillance programs. We report the first serological survey for plague in domestic carnivores conducted in California between 1979 and 1991 in five different settings or programs. A total of 4115 dogs and 466 cats were tested for plague antibody by the passive hemagglutination test. 86 dogs (2.09%) and 15 cats (3.22%) had plague antibody titers > or = 1:16. The percentage of positive dogs and cats were respectively 3.96% and 0% on reservations, 3.27% and 1.39% on military bases, 0.74% and 1.25% in Los Angeles County and 0% and 4.61% in veterinary clinics, but 41.38% and 41.2% from outbreak investigations. Titers ranged from 1:16 to 1:4096 in dogs and cats, but were low in dogs and cats in the Los Angeles County survey and on the military bases. Serologic testing of pets during human case investigation or increased rodent mortality should be regularly implemented, as well as dog surveys on reservations. Surveys of pet dogs in veterinary clinics did not appear worthwhile, even if selected from plague endemic regions. Veterinarians should report suspect cases in cats to public health authorities, that will improve plague surveillance and reduce the risk of humans contracting the disease from their pets.

PRO review. Part III: Quality review, intervention, and sanction.

The above material represents a detailed discussion of the GMCF quality review plan, the quality intervention plan, and the sanction plan. It should be clear that every effort is being made by GMCF-PRO to provide fair, realistic, and commonsense quality of care reviews to the physician and hospital community of Georgia. It should also be evident that GMCF interventions will focus on education. Practicing physicians of the appropriate specialty are involved at every level of the review, intervention, and sanction process. Due process is afforded to physicians and hospitals in each plan as described above. The practicing physician community should recognize the obvious need for active participation in the PRO review process to provide proper balance and perspective to quality of care reviews. The GMCF 29-member board (23 physicians) is committed to the concept of maintaining practicing physician involvement and participation in the HCFA-PRO program as mandated by Congressional legislation. It is necessary also for GMCF to continue with close communication to MAG and all specialty societies in order to ensure the recruitment of specialty physician consultants for a quality chart review program, review of screening criteria, and review committee participation.

Peer review in the 1990s. A look at the Georgia Medical Care Foundation.

Although it is not possible to completely summarize all of the policies and procedures of a program as complex as the PRO program in one article (or even three), it is useful for establishing the framework of these activities over the next 3 years. Many of us are skeptical of the government's role in the medical review process, and some of us can recall specific instances where problems, e.g., backlogs, have diverted us from our primary mission--to insure quality care. It is imperative, as we begin this new PRO contract, that we all recognize what the PRO program is and what it is not. Specifically, it is not a program of quotas wherein GMCF is required to produce a certain number of denials, quality problems, sanctions, etc. It is a peer review program funded by Medicare but implemented by Georgia physicians with a primary focus on quality review. A second point that needs to be made here concerns the scope of PRO findings relative to the volume of cases reviewed. As with any quality assurance program, it is necessary to look at many cases to determine if there are problems. It is important to note here that GMCF recognizes that most health care delivered in Georgia is appropriate. In fact, Mr. Thomas Morford, National PRO Program Director of the Health Care Financing Administration, recently testified to Congress as follows "clearly, the most important observation thus far is that the PROs have not uncovered any systemic quality problems in the Medicare program.(ABSTRACT TRUNCATED AT 250 WORDS)

Selected arthropod-borne diseases. Plague, Lyme disease, and babesiosis.

The incidence of plague, one of the oldest arthropod-borne diseases, has increased during the past 10 years in the United States. Domestic carnivores are playing an increased role in the occurrence of human cases. The cat is now the principal cause of primary human pneumonic plague in the United States. Lyme disease and babesiosis, which were initially thought to be limited to specific local regions, are much more widespread than originally thought.