Frailty Syndrome in Association with Depressive Symptoms and Functional Disability among Hospitalized Elderly

ABSTRACT

We sought to examine the frailty association with depression and functional disability in hospitalized older adults. In particular, we compared non-frail, pre-frail, and frail elderly hospitalized individuals. We performed a cross-sectional study with 255 hospitalized Brazilian elderly patients. We used a structured instrument to assess socio-economic data, the Fried frailty phenotype and used morbidity scales (Geriatric Depression; Katz; Lawton and Brody). The adjusted analysis revealed that frail elderly exhibit increased odds ratios (OR) for depressive symptoms (OR = 2.72, 95% CI: 1.12–6.62), disability related to basic activities (OR = 3.50, 95% CI: 1.26–9.60), and instrumental daily living (OR = 2.70, 95% CI: 1.12–6.44). Frailty in hospitalized older adults is associated with depressive symptomatology and functional disability.     

Differential antibody recognition of FC27-like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 × 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.     

Postoperative blood loss in coronary surgery. No real impact of fibrinolysis detected by thromboelastography and D-dimers. A prospective, randomized study

Although in many cardiac surgery centers pharmacological strategies based on fibrinolytic inhibitors are used on a routine basis, detailed knowledge of fibrinolysis during various settings of coronary surgery is still limited. Sixty-five patients scheduled for coronary surgery were randomized into 3 groups: group A--conventional coronary artery bypass grafting, group B--off-pump surgery, and group C--coronary artery bypass grafting with modified, rheoparin coated cardiopulmonary bypass with the avoidance of reinfusion of cardiotomy blood into the circuit. The sampling time points for rotation thromboelastographic evaluations were as follows: preoperatively, 15 minutes after sternotomy, on the completion of peripheral bypass anastomoses, at the end of the procedures, and 24 hours after the end of surgery. D-dimer levels were evaluated before surgery, at the end of procedures, and 24 hours after surgery. Thromboelastographic signs of fibrinolysis (evaluated by Lysis Onset Time-intergroup differences at 60 and 150 minutes of assessment: P = 0.003 and P < 0.001, respectively) were clearly detectable during cardiopulmonary bypass in group A, but not at any time in groups B and C. At the other sampling times all thromboelastographic parameters were similar in all groups. In group A, no exceptional bleeding tendency (during 24 hours), as compared to groups B and C (geometric means and 95% confidence intervals: group A: 686.7 [570.8; 826.1] mL, group B: 555.3 [441.3; 698.9] mL, group C: 775.6 [645.1; 932.3] mL, P = 0.157), and no significant correlations between Lysis Onset Time, postoperative blood loss, and D-dimer levels were found. No significant differences in postoperative blood loss related to cardiac surgeons and assistant surgeons were detected. Thromboelastographic signs of increased fibrinolysis were detectable in the important proportion of coronary surgery patients operated on with the use of conventional cardio-pulmonary bypass, but not in off-pump patients and those operated on with the biocompatible surface-modified circuit without reinfusion of cardiotomy suction blood. These signs resolved spontaneously at the end of surgery and were not associated with increased postoperative bleeding. No significant correlation with D-dimer levels was found.     

Detection and characterization of HIV type 2 in Calcutta, India

Since the first report of HIV/AIDS in India in 1986, continuous serosurveillance has been undertaken in all Indian states. Recently, five cases of HIV-2 infection have been detected in Calcutta, situated in the eastern part of India. The full-length envelope gene (2.5 kb) of one of the strains was amplified, cloned, and sequenced. Phylogenetic analysis of the Calcutta HIV-2 envelope revealed a close relatedness to the HIV-2 Rod sequence isolated in offshore Senegal. This strain, however, showed a genetic diversity of 13.5% to other Indian HIV-2 isolates.     

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5(-/-) bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5(-/-) bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms.     

Prevalence and Comorbidity of Insomnia and Effect on Functioning in Elderly Populations

A good night's sleep is often more elusive as we age, because the prevalence of insomnia in older people is high. Insufficient sleep can have important effects on daytime function by increasing the need to nap, reducing cognitive ability including attention and memory, slowing response time, adversely affecting relationships with friends and family, and contributing to a general sense of being unwell. However, rather than aging per se, circadian rhythm shifts, primary sleep disorders, comorbid medical/psychiatric illnesses, and medication use cause sleep difficulties in older people, which psychosocial factors may also affect. Clinicians should ask elderly patients about satisfaction with sleep. Any sleep complaints warrant careful evaluation of contributing factors and appropriate treatment.     

Early stage of adjuvant arthritis alters behavioral responses in male but not female rats

Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known about how inflammatory disease in its early stage, before any clinical manifestation, may affect general activity. The aim of this study was to compare the anxiety-like behaviour in the early stage of adjuvant arthritis (AA), and the paw edema, and corticosterone (CORT) levels in the developed stage of AA among male and female Long Evans rats. The behavioural activity was evaluated by elevated plus maze tests. These revealed significantly reduced number of entries into the open arm of the maze in arthritic males compared to controls or to females 4 days after AA induction. Arthrihtic and control females did not differ. The number of entries into the closed arm of the maze was the same across the genders and studied intervals. Time spent in the open arm was significantly lower in arthritic males against controls or arthitic females. Time spent in the closed arm showed inverse picture to the time spent in the open arm. Hind paw swelling measured on day 23 of AA was the same in males and females, as was the elevation of CORT levels in plasma. Male rats showed anxiety-like behaviour on day 4 of AA, while female rats did not show any change, indicating different brain sensitivity to early inflammation among the genders.     

Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with continuous neuronal loss. Treatment of clinical progression remains challenging due to lack of insights into inflammation-induced neurodegenerative pathways. Here, we show that an imbalance in the neuronal receptor interactome is driving glutamate excitotoxicity in neurons of MS patients and identify the MS risk–associated metabotropic glutamate receptor 8 (GRM8) as a decisive modulator. Mechanistically, GRM8 activation counteracted neuronal cAMP accumulation, thereby directly desensitizing the inositol 1,4,5-trisphosphate receptor (IP3R). This profoundly limited glutamate-induced calcium release from the endoplasmic reticulum and subsequent cell death. Notably, we found Grm8-deficient neurons to be more prone to glutamate excitotoxicity, whereas pharmacological activation of GRM8 augmented neuroprotection in mouse and human neurons as well as in a preclinical mouse model of MS. Thus, we demonstrate that GRM8 conveys neuronal resilience to CNS inflammation and is a promising neuroprotective target with broad therapeutic implications.     

Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.