Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

Prevalence and Associated Factors of Sarcopenia in Singaporean Adults—The Yishun Study

ObjectivesTo describe the normative values of sarcopenia among community-dwelling adults (≥21 years of age); compare the prevalence of sarcopenia using Asian Working Group for Sarcopenia criteria, 2014 (AWGS2014), Asian Working Group for Sarcopenia criteria, 2019 (AWGS2019), and European Working Group on Sarcopenia in Older People criteria, 2018 (EWGSOP2) guidelines; and identify factors associated with sarcopenia.DesignParticipants were recruited through random sampling. Sarcopenia assessments were performed using a dual-energy x-ray absorptiometry scan (muscle mass), handgrip test (muscle strength), and usual walking test (physical performance). Questionnaires were administered to evaluate lifestyle and cognition.Setting and ParticipantsIn total, 542 community-dwelling Singaporeans were recruited (21?90 years old, 57.9% women).MethodsWe assessed anthropometry, body composition, and questionnaire-based physical and cognitive factors, and estimated sarcopenia prevalence according to the AWGS2014, AWGS2019, and EWGSOP2 recommendations, and examined associations using logistic regression.ResultsAccording to AWGS2019, the Singapore population-adjusted sarcopenia prevalence was 13.6% (men 13.0%; women 14.2%) overall, and 32.2% (men 33.7%, women 30.9%) in those aged 60 years and above. The cut-offs derived from young adult reference group for low appendicular lean mass index were 5.28 kg/m2 for men and 3.69 kg/m2 for women (lower than AWGS recommended cut-off); for gait speed it was 0.82 m/s, (AWGS2019 recommended cut-off 1.0 m/s, AWGS2014 cut-off was 0.8 m/s); and for handgrip strength it was 27.9 kg/m2 for men and 16.7 kg/m2 for women (close to AWGS2019 recommendation). Age, sex, marital status, alcoholism, physical activity, body mass index, waist circumference, and global cognition were associated with sarcopenia (P < .05).Conclusions and ImplicationsThis is the first study to provide reference values of muscle mass, strength, and gait speed across the adult lifespan of Singaporeans. Using AWGS2019 criteria, sarcopenia is prominent in older age (32.2% in ≥60 years old), but it is already nontrivial (6.9%) among young and middle-age persons. Multidomain lifestyle modifications addressing muscle strength, cognition, and nutrition over the adult lifespan are important to delay the development of sarcopenia.     

The use of clonogenic assays in assessing the response of human lung cancer cell lines to alpha and gamma interferons alone or in combination with adriamycin

The antiproliferative and cytotoxic effects of purified IFN-alpha and recombinant IFN-gamma were investigated using both direct cell counting and a clonogenic assay on a panel of 5 established human lung cancer cell lines and for 2 of them also on their multidrug-resistant counterparts. There was considerable heterogeneity in the response of the cell lines to the IFNs in terms of growth inhibition. Clonogenic assay of IFN-treated cells indicated that, where a cell line had responded markedly to an IFN, only a small fraction of the cells remaining after IFN treatment were clonogenically viable. When cells were placed into the clonogenic assay in the presence of IFNs, the time course of colony formation was different from that seen in the control cultures for most of the cell lines. The measured "surviving fraction" was greatly dependent upon the time of colony counting. When the effects of IFNs in combination with ADM were studied, conclusions regarding the interaction of the effects of the agents also depended upon the time at which colonies were counted.     

Household and environmental factors influencing anthropometric outcomes in preschool children in a rural Ethiopian community

This article tests the hypothesis that anthropometrical outcomes in preschool children are a function of complex interaction between food, nutrition, health, and other physical environmental conditions within which children live and grow. A system of simultaneous equations is used to test the above hypothesis using data from an Ethiopian highland community. The results show that a child's nutritional and health status are jointly determined by dietary intake, well-being of the mother as the primary caregiver, and the state of the physical environment for agricultural production and healthy living. Among other factors, children were found to be in better health with an increase in the number of cows in their households' livestock herds. The revealed interrelatedness and complexities of cause and effect clearly dictate the need for a multi- or transdisciplinary approach to research and development addressing health, nutrition, sanitation, agricultural production practices, among other factors for alleviating the nutritional and health problems of children and rural households.     

Reverse Peroneal Artery Flap—A Workhorse Flap for Reconstruction of Large,Distal Defects of Ankle and Foot

Background  Reconstruction of large foot and ankle defects is a difficult task due to less available local soft tissue and more critical from functional point of view. To overcome the limitations associated with locoregional flaps and free flaps, reverse peroneal artery (RPA) flap was selected and its usefulness in reconstruction of distal large defects of the ankle and foot and its complications were studied. Materials and Methods  This is a prospective observational study done in 20 patients treated as cohort within 2 years and 8 months from January 2018 to August 2020. Large defects of foot and ankle were reconstructed with RPA flap and evaluated for its usefulness. Three cases were evaluated with computed tomography angiography postoperatively, to assess the vascular pattern. Conclusion  RPA flap is a versatile and very reliable flap for the reconstruction of large and distal defects of foot and ankle. It is safely done in children and in acute trauma without any major complications.     

Thyroid Hormones and Cardiovascular Function and Diseases

Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality. Experimental data and small clinical trials have suggested a beneficial role of TH in ameliorating CV disease. The aim of this review is to provide clinicians dealing with CV conditions with an overview of the current knowledge of TH perturbations in CV disease.