Association of decreased frequency of conversation with depression, oral function and eating alone: A cross-sectional study of older adults during the COVID-19 pandemic.

AIM: This study examined the associations between geriatric factors and decreased opportunities for conversation among older adults amid a period of self-restraint during the COVID-19 pandemic. METHODS: A cross-sectional questionnaire-based survey was carried out in October 2020. The participants were 204 residents aged ≥65 years staying at a private care home in Kyoto city, Japan. Logistic regression analysis was carried out with the reduction of conversation opportunities as the dependent variable, and geriatric factors as independent variables after adjusting for age and sex. We compared the decreased frequency of opportunities between residents in the assisted living wing and in the nursing care wing of the private care home. RESULTS: The percentages of respondents who reported a decrease in the opportunities for conversation among themselves were 43.9% for residents in the assisted living wing and 19.7% for those in the nursing care wing. After adjusting for age and sex, the opportunities for conversation was significantly associated with the basic activities of daily living (OR 1.07, 95% CI 1.01-1.12), instrumental self-maintenance (OR 1.25, 95% CI 1.08-1.46), intellectual activity (OR 1.35, 95% CI 1.09-1.66), depression (OR 1.13, 95% CI 1.04-1.23), depressive mood (OR 3.83, 95% CI 1.98-7.42), decreased motivation (OR 3.11, 95% CI 1.58-6.12), appetite loss (OR 4.32, 95% CI 1.54-12.07), swallowing function (OR 1.05, 95% CI 1.00-1.10), chewing difficulty (OR 2.50, 95% CI 1.31-4.75) and eating alone (OR 2.5, 95% CI 1.35-4.62). CONCLUSION: Decreased opportunities for conversation was more perceived among older adults with higher daily functioning, suggesting that it is associated with depressed mood, oral function and solitary eating. Geriatr Gerontol Int 2024; 24: 385-391.

Association between glucose tolerance and mortality among Japanese community-dwelling older adults aged over 75 years: 12-year observation of the Tosa Longitudinal Aging Study.

AIM: Although the relationship between impaired glucose tolerance (IGT) and mortality has been investigated in diverse populations, few studies have focused on older populations. This study aimed to investigate the relationship between glucose tolerance and overall mortality among populations aged ≥75 years. METHODS: Data were obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey conducted in Kochi, Japan. According to the results of a 75-g oral glucose tolerance test conducted in 2006, the participants were classified into four categories: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/IGT, newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM). The primary endpoint was overall mortality. Differences in overall mortality among the four categories were evaluated using the Cox proportional hazards model. RESULTS: During a median of 11.5 years of observation, 125 deaths of the 260 enrolled participants were recorded. The cumulative overall survival rate was 0.52, and the survival rates of NGT, IFG/IGT, NDM, and KDM were 0.48, 0.49, 0.49, and 0.25, respectively (log-rank test, P = 0.139). Adjusted hazard ratios (HRs) for mortality in the IFG/IGT and NDM groups compared with the NGT group were 1.02 (95% confidence interval [CI], 0.66-1.58) and 1.11 (95% CI, 0.56-2.22), while mortality in the KDM group was significantly higher than that in the NGT group (HR, 2.43; 95% CI, 1.35-4.37). CONCLUSION: Mortality did not differ significantly between the IFG/IGT, NDM, and NGT groups, but was higher in the KDM group than in the NGT group. Geriatr Gerontol Int 2023; 23: 341-347.

Older adults' preferences for and actual situations of artificial hydration and nutrition in end-of-life care: An 11-year follow-up study in a care home.

AIM: To clarify older adults' preferences for and actual situations of artificial hydration and nutrition (AHN) in end-of-life care in a care home. METHODS: Participants were residents of a care home who had completed advance directives regarding preferred methods of AHN from 2009 to 2018. Advance directives alone were available from April 2009 to June 2016 (Wave 1), and advance care planning for AHN including advance directives was introduced in July 2016 (Wave 2). AHN preferences included (i) intensive methods (percutaneous endoscopic gastrostomy, nasogastric tube feeding and total parenteral nutrition), (ii) drip infusion, and (iii) oral intake only. Participants were followed until the end of 2020, and we checked whether decisions about AHN were based on older adults' preferences. RESULTS: In total, 272 participants had completed advance directives. Most participants preferred "oral intake only" (59.5%), followed by drip infusion (32.0%) and intensive methods (8.5%) in advance directives. Ninety of the 272 participants completed advance directives twice; 83.3% did not change their AHN preferences from Wave 1 to Wave 2. By the end of 2020, 93 of the 272 participants died in the care home. AHN was provided according to older adults' preferences in 48.9% (oral intake only), in 51.4% (drip infusion) and in 55.6% (intensive methods) of cases respectively. CONCLUSIONS: Most participants preferred oral intake only, and their preferences were reflected in decisions about actual situations of AHN in end-of-life care. To prepare for advanced dementia and senility, early advance care planning for AHN should be promoted. Geriatr Gerontol Int 2022; 22: 581-587.

Gynecological aspects as a component of comprehensive geriatric assessment: A study of self-rated symptoms of pelvic organ prolapse among community-dwelling elderly women in Japan.

OBJECTIVES: Despite the reported 'male-female health-survival paradox', no components of the comprehensive geriatric assessment (CGA) routinely used in the field of geriatrics focus on female-specific symptoms. To investigate the impact of gynecological factors among elderly women, we noted the gynecological history and examined the association between self-rated symptoms of pelvic organ prolapse (POP) and CGA. STUDY DESIGN: This community-based, cross-sectional study in Japan included 164 community-dwelling women aged ≥75 years. MAIN OUTCOME MEASURES: The main outcome measures were the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), activities of daily living (ADL), and Timed Up and Go (TUG) test. Self-rated symptoms of POP were assessed using POPDI-6, and the participants were dichotomized into POPDI-6 >0 (symptom group) and POPDI-6 = 0 (no-symptom group). Several components of the CGA were compared between the groups with and without symptoms of POP and the association with POPDI-6 score was analyzed by multiple logistic regression analysis. RESULTS: Compared with the no-symptom group, the symptom group had significantly longer TUG test time (≥13.5 s) (P = 0.024) and difficulty in basic ADL (score <21) (P = 0.02). In multiple logistic regression analysis, basic ADL <21 and TUG time ≥13.5 s were significantly associated with POPDI-6 >0 (odds ratio [OR] = 2.78; 95% confidence interval [CI] = 1.10-7.06 and OR = 3.45; 95% CI = 1.01-1.24). CONCLUSIONS: Self-rated POP symptoms were associated with CGA components among community-dwelling elderly women. Evaluating POP symptoms as part of the CGA could be meaningful for improving physical and psychological health in elderly women.

Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland.

OBJECTIVES: To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. DESIGN: Cross-sectional epidemiological study on Tibetan highlanders. PARTICIPANTS: We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). MAIN OUTCOME MEASURE: Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. RESULTS: The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance. CONCLUSIONS: Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing.

Predictors of difficulty in carrying out basic activities of daily living among the old-old: A 2-year community-based cohort study.

AIM: To present practical predictors for the difficulty of carrying out basic activities of daily living (ADL) among the old-old during a 2-year period. METHODS: Assessment was carried out using data obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey on geriatric functions in the elderly. Predictor variables measured at baseline included age; sex; height; weight; blood pressure; oxygen saturation; neurobehavioral functions, such as Mini-Mental State Examination, Kohs Block Design test, Timed Up and Go test, button score, functional reach test, geriatric depression scale, cardio-ankle vascular index, ankle brachial pressure index; and blood chemical results, such as hemoglobin, fasting blood sugar, hemoglobin A1c, serum lipids, serum albumin and serum creatinine. The outcome variable was the presence of difficulties while carrying out basic ADL after 2 years. RESULTS: Age of ≥85 years, Timed Up and Go test of ≥15 s, button score of >17 s and presence of knee pain were independent predictors of difficulty in carrying out basic ADL after 2 years. Elderly individuals who have had at least two positive findings out of these four variables were likely to have impaired basic ADL during a 2-year period with a positive predictive value of 52.0%, negative predictive value of 90.2%, sensitivity of 70.3% and specificity of 80.8%. CONCLUSIONS: Assessment of age, Timed Up and Go test, manual dexterity, and presence of knee pain is a useful and relevant way to identify patients who should be informed about their likelihood of developing difficulties in carrying out basic ADL.

Oxidized Low Density Lipoprotein Among the Elderly in Qinghai-Tibet Plateau.

OBJECTIVE: Several environmental factors including hypoxia have been reported to contribute to oxidative stress in individuals living in the highlands. However, little is known about the role of oxidized low-density lipoprotein (ox-LDL) among community-dwelling elderly in the Qinghai-Tibet plateau. METHODS: The study population comprised 168 community-dwelling elderly subjects aged 60 years or older (male to female ratio, 70:98; mean age, 65.8 years) living in Haiyan County, located 3000 to 3200 m above sea level, 30 km northwest of Xining, Qinghai. The subjects were volunteers who joined a Comprehensive Geriatric Assessment. Plasma ox-LDL was measured in 168 community-dwelling elderly subjects aged 60 years or older (23 Tibetans and 145 Hans) with a monoclonal antibody-based enzyme-linked immunosorbent assay. RESULTS: Mean ox-LDL level was higher among Tibetan elderly than Han elderly (Tibetan, 79.0 ± 29.6 U/L; Han, 62.8 ± 23.5 U/L; P = .003). Tibetan ethnicity was significantly associated with ox-LDL levels after adjusting for LDL cholesterol levels. In addition, high ox-LDL levels (≥70 U/L) were significantly associated with a homeostasis model assessment insulin resistance index of at least 1.6 (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to 7.15; P = .029) and ankle brachial pressure index of less than 1.0 (OR, 4.85; 95% CI, 1.14 to 10.00; P = .028), after adjusting for age, sex, and ethnicity. CONCLUSIONS: Our findings support the hypothesis that ox-LDL levels are higher among Tibetan elderly highlanders compared with those among Han elderly. As ox-LDL levels can affect insulin resistance and arteriosclerosis, further research is needed to determine how oxidative stress influences the health situation among elderly individuals at high altitudes.

Conjugated linoleic acids inhibit hypoxia inducible factor-1α stabilization under hypoxic condition in human hepatocellular carcinoma cells.

The anti-cancer effects of various fatty acids are drawing a lot of attention. To determine whether different fatty acids affect the hypoxic response of liver cancer cells, we examined the effects of various fatty acids on the stabilization of the hypoxia-inducible factor (HIF)-1α protein in the HepG2 human hepatocellular carcinoma (HCC) cell line under condition containing 1% O(2). Of the fatty acids examined, only 9cis, 11trans (c9, t11)-conjugated linoleic acid (CLA) and 10trans, 12cis (t10, c12)-CLA inhibited hypoxia-induced HIF-1α stabilization. In addition, HIF-1α prolyl hydroxylase or proteasome inhibition abrogated the effects of c9, t11- and t10, c12-CLA. Moreover, c9, t11- and t10, c12-CLA significantly inhibited cell proliferation and induced apoptotic cell death under hypoxia. This is the first study showing that c9, t11- and t10, c12-CLA inhibit the hypoxic response in HCC cells.

Malformation spectrum induced by ketoconazole after single administration to pregnant rats during the critical period - comparison with vitamin A-induced malformation spectrum.

Azole derivatives have teratogenic effects in rodents. In the present study, malformations and their sensitive windows induced by high-dose ketoconazole (KCZ), an azole derivative, without maternal toxicity were investigated. In addition, the malformation spectrum determined was compared with that induced by vitamin A palmitate (VAP). Pregnant rats were administered a single dose of KCZ by oral gavage on specific individual days from gestational days 8 to 15 (GDs 8-15). Maternal animals were subjected to necropsy on GD 20, and the obtained fetuses were examined for external, visceral and skeletal malformations. The malformation spectrum of VAP was identified from available published data (Noda, Sato, and Udaka, 1982) and a complementary study (single administration of VAP at 1 200 000 IU kg(-1) ). Embryonic lethality was observed in dams given KCZ on GDs 9-12 with peak incidence on GDs 10 and 11 with complete resorption. KCZ induced major malformations included cleft palate, digital anomalies, misshapen limbs and unique discontinuous ribs, and the sensitive window for each was identified. Compared with the malformations induced by VAP, unique malformations (e.g. discontinuous ribs by KCZ, neural tube defects by VAP), similar malformations with similar sensitive windows (e.g. digital and limb malformations) and similar malformations with different sensitive windows (e.g. embryonic lethality and cleft palate) were distinguished, suggesting that the mechanisms of several of the types of KCZ-induced malformation are related to excessive vitamin A.

Ultrasound-guided needle aspiration of epidural hematoma in a neonate after vacuum-assisted delivery.

INTRODUCTION: Epidural hematoma (EDH) is a rare complication of vacuum-assisted delivery in neonates. Although the standard treatment of EDH is surgical evacuation via craniotomy, it is an invasive procedure in neonates, and less invasive methods may be favored for hematoma evacuation. CASE REPORT: We report a case of 5-day-old infant with a massive EDH, cephalohematoma, and a depressed fracture, which were secondary to a vacuum-assisted delivery and cured by ultrasound-guided needle aspiration and drainage. Neonatal EDH may be different from adult counterpart in that the former is more liquefied and is amenable to needle aspiration than the latter. Although needle aspiration is a blind procedure, addition of transcranial ultrasound not only ensures safety by visualizing the tip of the needle but also makes real-time evaluation of the residual hematoma volume possible.

EF6265, a novel inhibitor of activated thrombin-activatable fibrinolysis inhibitor, protects against sepsis-induced organ dysfunction in rats.

OBJECTIVE: Although thrombin-activatable fibrinolysis inhibitor (TAFI) has been implicated as a negative regulator of fibrinolysis, its pathophysiological significance remains to be unveiled. We performed the pharmacologic study to assess the effect of EF6265, a specific inhibitor of activated form of TAFI (TAFIa) on sepsis-induced organ dysfunction models. DESIGN: A controlled, in vivo laboratory study. SETTING: Company research laboratory. SUBJECTS: Wistar and Sprague-Dawley rats. INTERVENTIONS: Endotoxemia and sepsis models were induced by intravenous injection of lipopolysaccharide and Pseudomonas aeruginosa, respectively. MEASUREMENTS AND MAIN RESULTS: In the endotoxemia model, posttreatment (1 hour) with EF6265 reduced fibrin deposits in the kidney and liver accompanied by no significant changes in platelet count and fibrinogen concentration in plasma. This compound also significantly decreased levels of plasma lactate dehydrogenase and aspartate aminotransferase, markers of organ dysfunction. In the sepsis model, EF6265, simultaneously administered with ceftazidime (CAZ) 2 hours after Pseudomonas aeruginosa injection, showed no influence on the antibiotic activity of CAZ. Meanwhile, it dramatically potentiated the interleukin-6-reducing effect of CAZ in plasma, suggesting that inhibition of TAFIa leads to the reduction in systemic inflammatory response associated with bacterial infection. This combined treatment also lowered plasma lactate dehydrogenase and blood urea nitrogen more potently than single treatment with CAZ. CONCLUSIONS: These results clearly suggest that TAFI plays an important role in the deterioration of organ dysfunction in sepsis and the inhibitor of TAFIa protects against sepsis-induced tissue damage through regulation of fibrinolysis and inflammation.

Enhancement of fibrinolysis by EF6265 [(S)-7-amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl] methyl]heptanoic acid], a specific inhibitor of plasma carboxypeptidase B.

Plasma procarboxypeptidase B, also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is converted by thrombin into the active enzyme, carboxypeptidase B (CPB)/activated TAFI. Plasma CPB down-regulates fibrinolysis by removing carboxy-terminal lysines, the ligands for plasminogen and tissue-type plasminogen activator (tPA), from partially degraded fibrin. To target thrombosis in a new way, we have identified and optimized a phosphinic acid-containing inhibitor of CPB, EF6265 [(S)-7-amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino) propyl]hydroxyphosphinoyl]methyl]heptanoic acid] and determined both the pharmacological profile and pathophysiological role of CPB in rat thrombolysis. EF6265 specifically inhibited plasma CPB activity with an IC(50) (50% inhibitory concentration) of 8.3 nM and enhanced tPA-mediated clot lysis in a concentration-dependent manner. EF6265 decreased detectable thrombi (percentage of glomerular fibrin deposition; control, 98 +/- 1.1; EF6265, 0.1 mg/kg, 27 +/- 9.1) that had been generated by tissue factor in a rat microthrombosis model with concomitant increases in plasma D-dimer concentration (control, <0.5 microg/ml; EF6265, 0.1 mg/kg, 15 +/- 3.5 microg/ml). EF6265 reduced plasma alpha2-antiplasmin activity to a lesser extent than tPA. In an arteriovenous shunt model, EF6265 (1 mg/kg) enhanced exogenous tPA-mediated thrombolysis under the same conditions that neither EF6265 nor tPA (600 kIU/kg) alone reduced thrombi. EF6265 (1 and 30 mg/kg) did not affect the bleeding time in rats. Moreover, it did not prolong the bleeding time evoked by tPA (600 kIU/kg). These results confirm that circulating procarboxypeptidase B functions as a fibrinolysis inhibitor's zymogen and validates the use of CPB inhibitors as both an enhancer of physiological fibrinolysis in microcirculation and as a novel adjunctive agent to tPA for thromboembolic diseases while maintaining a small effect on primary hemostasis.