Prevalence of Dementia and Mild Cognitive Impairment in the Rural Island Town of Ama-cho, Japan

Aims: In order to determine the prevalence of dementia and mild cognitive impairment (MCI), we conducted a population-based study in Japan. Methods: Participants included 924 subjects aged 65 years or older who resided in the town of Ama-cho. In phase 1 of the study, the Mini-Mental State Examination and Clinical Dementia Rating were administered for screening purposes. In phase 2 of the study, the subjects who screened positive were further examined by neurologists. Dementia and MCI were diagnosed by means of DSM-IV and International Working Group on MCI criteria, respectively. Results: By the prevalence date of June 1, 2010, 24 subjects had deceased or lived outside the town. In total, 723 of the remaining 900 subjects received a phase 1 test. In phase 2, 98 subjects were diagnosed with amnestic MCI, 113 subjects with non-amnestic MCI, and 82 subjects with dementia. Of the subjects who did not receive the phase 1 test, 66 subjects were diagnosed as having dementia according to data from their town medical card or the Long-term Care Insurance System. The crude prevalence of amnestic MCI, non-amnestic MCI, and dementia were 10.9, 12.6, and 16.4%, respectively. Conclusion: Consistent with the striking increase in the number of elderly individuals, we report higher prevalence of MCI and dementia in Japan than previously described

Frail patients with respiratory failure

Background : Older patients with severe respiratory failure have higher mortality rates and are more likely to experience impairments in activities of daily living (ADL). Methods : We retrospectively reviewed patients (≥ 75 years) who received intubation and artificial ventilation for respiratory failure at Shimane University Hospital between November 2014 and December 2020. We compared the outcomes of frail patients with those of self-sufficient patients. Results : Thirty-two patients were included. ADL ability before respiratory failure was rated self-sufficient in 18 patients (self-sufficient group) and not self-sufficient in 14 patients (frail group). None of the patients in either group underwent advanced care planning prior to the onset of respiratory failure. In the self-sufficient and frail groups, the in-hospital mortality rates were 33% and 50%, and the incidence of bedridden patients at discharge was 6% and 43%, respectively. Most patients in the frail group (93%) died or were bedridden. The median hospitalization cost was JPY 2,984,000 for the self-sufficient group and JPY 3,008,000 for the frail group. Conclusion : The overall prognosis of frail older patients who underwent intubation and artificial ventilation was poor. When providing intensive care to such patients, it is important to carefully consider their suitability for the treatment

Molecular Analysis of Common Types ofﾎｱ-Thalassemia Associated with(ﾎｲ-Thalassemia in Northern Thailand

We applied PCR strategies to detect the common types of ﾎｱ- thalassemia determinants which were associated with ﾎｲ- thalassemia in northern Thailand. Two types of deletions in the ﾎｱ-globin gene locus;the 18 kb deletion of Southeast Asian type(-ﾎｱSEA)and the 3.7 kb rightward deletion(-ﾎｱ3.7), and the most prevalent non-deletion mutation, Hb Constant Spring(ﾎｱC8, TAA to CAA at the codon 141)were investigated in 22 cases of ﾎｲ-thalassemia. Nine ﾎｲ-thalassemia patients were found to be associated with one or two of these defective ﾎｱ-globin gene determinants and the mean hemoglobin concentration in these patients was 6.3 ﾂｱ 1.1 g/dl whereas it was 5.6ﾂｱ.0.8 g/dl in 12 ﾎｲ-thalassemia patients without ﾎｱ- globin gene abnormalities ; the difference is statistically insignificant (p = 0.08). The level of anemia was severe in the ﾎｲ-thalassemia patients carrying a single ﾎｱ-globin gene abnormality in the heterozygous compounds ; whereas the (ﾎｲ-thalassemias withﾎｱ-globin gene defects in both alleles showed less severe anemia. A patient carrying the ﾎｱ ・｣8 determinant in homozygous compound showed the highest hemoglobin level among these ﾎｲ-thalassemia patients

GPS and chemotherapy for elderly NSCLC

Background : Although platinum-combination chemotherapy is widely used to treat advanced non-small cell lung cancer (NSCLC), not all elderly patients benefit from this regimen. In this retrospective study, we aimed to evaluate whether the Glasgow Prognostic Score (GPS), an indicator of systemic inflammation and malnutrition, could predict the tolerability and efficacy of platinum-combination chemotherapy among elderly patients with NSCLC. Methods : The eligibility criteria included patients aged ≥ 70 years with NSCLC treated with first-line platinum-combination chemotherapy at Shimane University Hospital between January 2015 and December 2018. Results : Thirty-two patients with NSCLC (median age, 74 years) were included. The GPS scores were 0–1 for 19 patients and 2 for 13 patients. Four chemotherapy cycles were completed by 57.9% and 30.8% of patients in the GPS 0–1 and GPS 2 groups, respectively. The GPS 0–1 group experienced better outcomes than the GPS 2 group (response rate : 26% vs. 15%, P = 0.67 ; median progression-free survival : 4.1 vs. 2.1 months, P = 0.0026 ; median overall survival : 22.8 vs. 9.6 months, P = 0.0092). Conclusions : Platinum-combination chemotherapy demonstrated promising efficacy among elderly NSCLC patients with a GPS 0–1. Therefore, GPS may be crucial in determining whether treatments recommended for younger patients are suitable for older patients with NSCLC

Studies on Expression of Aldehyde Dehydrogenase in Normal and Cancerous Tissues of Thyroids

Recently published articles have reported the controversial data regarding expression of aldehyde dehydrogenase isozyme 1A1 (ALDH1A1), a potential candidate marker for normal and cancer stem cells (CSCs), in thyroid tissues. These data prompted us to re-evaluate expression of ALDH1A1 in normal and cancerous thyroid tissues by 2 different means. The first method was immunohistochemistry with 2 different anti-ALDH1A1 antibodies from distinct companies. Following validating the integrity of these 2 antibodies by Western blotting with ALDH-expressing and nonexpressing cancer cell lines and immunohistochemistry with breast and colon tissues, we report here significant and comparable expression of ALDH1A1 in both normal and cancerous thyroid tissues with both antibodies. Next, relative expression levels of ALDH isozymes were evaluated by reverse transcription-polymerase chain reaction (RT-PCR), revealing that ALDH1A1 was the most highly expressed isozyme followed by ALDH9A1 and relative expression patterns of isozymes were very similar in normal and cancerous tissues. All these data demonstrate that thyroid cells of normal and cancer origins do express ALDH1A1 and to a lesser extent 9A1. Further study will be necessary to study functional significance of ALDH1A1 in the function and behaviors of thyroid normal and cancer stem cells

甲状腺刺激ホルモンシグナルは、BRAFV600E甲状腺癌マウスモデルにおけるゲノム不安定性を伴った高度悪性化に関与している

長崎大学学位論文 [学位記番号]博（医歯薬）甲第636号 [学位授与年月日]平成25年10月2

Static and dynamic hypergravity responses of osteoblasts and osteoclasts in medaka scales

Fish scales are a form of calcified tissue similar to that found in human bone. In medaka scales, we detected both osteoblasts and osteoclasts and subsequently developed a new scale assay system. Using this system, we analyzed the osteoblastic and osteoclastic responses under 2-, 3-, and 4-gravity (G) loading by both centrifugation and vibration. After loading for 10 min, the scales from centrifugal and vibration loading were incubated for 6 and 24 hrs, respectively, after which the osteoblastic and osteoclastic activities were measured. Osteoblastic activity significantly increased under 2- to 4-G loading by both centrifugation and vibration. In contrast, we found that osteoclastic activity significantly decreased under 2- and 3-G loading in response to both centrifugation and vibration. Under 4-G loading, osteoclastic activity also decreased on centrifugation, but significantly increased under 4-G loading by vibration, concomitant with markedly increased osteoblastic activity. Expression of the receptor activator of the NF-αB ligand (RANKL), an activation factor of osteoclasts expressed in osteoblasts, increased significantly under 4-G loading by vibration but was unchanged by centrifugal loading. A protein sequence similar to osteoprotegerin (OPG), which is known as an osteoclastogenesis inhibitory factor, was found in medaka using our sequence analysis. The ratio of RANKL/OPG-like mRNAs in the vibration-loaded scales was significantly higher than that in the control scales, although there was no difference between centrifugal loaded scales and the control scales. Accordingly, medaka scales provide a useful model by which to analyze bone metabolism in response to physical strain. © 2013 Zoological Society of Japan

Postnatal Expression of BRAFV600E Does Not Induce Thyroid Cancer in Mouse Models of Thyroid Papillary Carcinoma

The mutant BRAF (BRAFV600E) is the most common genetic alteration in papillary thyroid carcinomas (PTCs). The oncogenicity of this mutation has been shown by some genetically engineered mouse models. However, in these mice, BRAFV600E is expressed in all the thyroid cells from the fetal periods, and suppresses thyroid function, thereby leading to TSH elevation, which by itself promotes thyroid tumorigenesis. To overcome these problems, we exploited 2 different approaches, both of which allowed temporally and spatially restricted expression of BRAFV600E in the thyroid glands. First, we generated conditional transgenic mice harboring the loxP-neoR-loxP-BRAFV600Einternal ribosome entry site-green fluorescent protein sequence [Tg(LNL-BRAFV600E)]. The double transgenic mice (LNL-BRAFV600E;TPO-Cre) were derived from a high expressor line of Tg(LNLBRAFV600E) mice and TPO-Cre mice; the latter expresses Cre DNA recombinase under the control of thyroid-specific thyroid peroxidase (TPO) promoter and developed PTC-like lesions in early life under normal serum TSH levels due to mosaic recombination. In contrast, injection of adenovirus expressing Cre under the control of another thyroid-specific thyroglobulin (Tg) promoter (Ad-TgP-Cre) into the thyroids of LNL-BRAF V600E mice did not induce tumor formation despite detection ofBRAFV600EandpERKin a small fraction of thyroid cells. Second, postnatal expression ofBRAFV600E in a smallnumberof thyroid cellswasalso achieved by injecting the lentivirus expressing loxP-green fluorescent protein-loxP-BRAFV600E into the thyroids of TPO-Cre mice; however, no tumor development was again observed. These results suggest that BRAFV600E does not appear to induce PTC-like lesions when expressed in a fraction of thyroid cells postnatally under normal TSH concentrations