Cognitive dysfunction: An emerging concept of a new diabetic complication in the elderly

The incidence of type 2 diabetes mellitus (T2DM) has risen, and this trend is likely to continue. Recent advances suggest that T2DM is a risk factor for cognitive decline. We are now encountering novel complications of T2DM, namely cognitive dysfunction and dementia. Although the treatment strategy for diabetic patients with neurocognitive dysfunction has received a great deal of attention, the appropriate level of glycemic control for the prevention of the development and/or progression of cognitive decline in elderly diabetic patients remains to be elucidated. Another issue in diabetic treatment in patients with cognitive dysfunction is the selection of medicines. The best choice and combination of antidiabetic medications for the preservation of cognition should also be studied. Ample studies suggest that exercise helps to preserve cognitive function, although existing evidence does not necessarily indicate its effectiveness exclusively in diabetic patients. Exercise is a helpful non‐pharmacological therapy. Considering the progressive aging of the worldwide population, more research to investigate the best way to manage this population is important. Geriatr Gerontol Int 2012; ••: ••–•• .     

Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia

Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes.     

Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 μM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 μM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites.     

Clinical features of bilateral acute idiopathic maculopathy

PURPOSE: To describe the clinical course of bilateral acute idiopathic maculopathy (BAIM), and to analyze its pathophysiology. CASE: A 33-year-old Japanese woman presented with a sudden, severe, bilateral visual disturbance following a flu-like illness. She was examined by fluorescein angiography (FA), indocyanine green angiography (IA), scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and multifocal electroretinography (mfERG). OBSERVATIONS: A diagnosis of BAIM was made in this patient based on typical ophthalmoscopic features, which included a pathognomonic yellowish-white foveal lesion. FA demonstrated a breakdown of the outer blood-retinal barrier, with the size and location corresponding to the white lesion, and IA disclosed a choroidal circulatory disturbance. SLO demonstrated that the deep retinal and choroidal layers were disorganized, and OCT showed retinal edema. Electrophysiological dysfunction was detected by mfERGs. After steroid therapy, the patient's visual acuity recovered to normal. The pooling of fluorescein dye and the OCT-determined retinal edema were resolved. However, the physiological dysfunction detected by mfERGs remained. CONCLUSIONS: We conclude that the major abnormality in BAIM is an alteration of the retinal pigment epithelium causing severe edema.     

Clinicopathological study of experimentally induced canine monocytic ehrlichiosis

The aims of this study are to investigate the hematology, blood chemistry, pathological study, including macroscopic and microscopic lesions, of experimentally induced canine monocytic erhlichiosis in Thailand and to demonstrate the distribution of Ehrlichia canis in target organs by nested polymerase chain reaction (PCR). Five experimental healthy dogs were inoculated with 5 ml of whole blood (estimated number of E. canis morulae 15 × 10^–5% per monocytes) from the splenectomized dog via the saphenous vein. Two healthy dogs served as a negative control. Hematology revealed nonregenerative normocytic normochromic anemia, thrombocytopenia and mild leukopenia. Blood chemistry revealed an increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AP), hypoproteinemia, hypoalbuminemia, and hyperglobulinemia by day 66 post-inoculation. Pathology revealed anemia, ascites, jaundice, interstitial pneumonia, splenomegaly, generalized lymphadenopathy, and severe fatty liver. The detection of E. canis was performed using tissue embedded in paraffin wax by nested PCR showing positive in all target organs. This study concluded that acute induced experimental canine monocytic ehrlichiosis can cause significant clinical and pathological lesions.     

The metaphor and sarcasm scenario test: a new instrument to help differentiate high functioning pervasive developmental disorder from attention deficit/hyperactivity disorder

It is sometimes difficult to discriminate high functioning pervasive developmental disorders (HFPDD) from attention deficit/hyperactivity disorders (AD/HD) in young children because of the behavioral similarities between the two. For adequate diagnosis, understanding fundamental differences in their social cognitive abilities might become significant. In order to detect the differences in social cognitive abilities between AD/HD and HFPDD, a new test, the Metaphor and Sarcasm Scenario Test (MSST) was developed. One hundred and ninety-nine normal school children (the control group), 29 AD/HD children and 54 HFPDD children were involved. The results showed that the inability to understand a sarcastic situation was specific to children with HFPDD, both children with AD/HD and HFPDD could not equally understand metaphor. The correlation between the comprehension of sarcasm and success in the theory of mind task was remarkably high but not for comprehension of metaphor. In conclusion, the MSST has the potential to discriminate HFPDD from AD/HD in young children.     

Analytical studies of both initial symptoms and clinical symptoms and signs of different etiologies of chronic pancreatitis: an approach by using odds ratios]

We conducted the statistical analysis of both initial symptoms and clinical symptoms and signs of different etiologies of chronic pancreatitis by using odds ratios which was one of the techniques of evidence-based medicine. The official report published by The Research Group of Intractable Pancreatic Diseases sponsored by the Welfare Ministry of Japan in 1986 was available as the data source of the present study. Nine items of initial symptoms and 25 items of 28 clinical symptoms and signs were compared in 4 different etiologies of the disease which were alcoholic, biliary, idiopatic and nonalcoholic (both biliary and idiopatic). In initial symptoms, 1.5 items were significantly more observed in alcoholic pancreatitis than in nonalcoholic, biliary and idioatic pancreatitis, 4 of which (abdominal pain, back pain, poor appetite and loss of body weight) were common items as might be related closely to the alcohol intake, 2. only one item of jaundice was significantly more observed in biliary pancreatitis than in alcoholic and idiopatic pancreatitis, 3.3 items of poor appetite, diarrhea and abdominal mass were more frequently observed in idiopatic pancreatitis than in biliary pancreatitis. In clinical symptoms and signs, 1. almost all items (21 to 24) were significantly more observed in alcoholic pancreatitis than in the other etiologies of the disease, and seemed to be related directly or indirectly to alcohol intake, 2.3 or 4 items which were related closely to gallstone and acute cholecystitis were significantly more observed in biliary pancreatitis than the other two etiologies of the disease, and 3.4 items consisting of diarrhea, loss of body weight, and pancreatic swelling were more frequently observed in idiopathic pancreatitis than in biliary pancreatitis.     

Medial prefrontal cell activity signaling prediction errors of action values

To adapt behavior to a changing environment, one must monitor outcomes of executed actions and adjust subsequent actions accordingly. Involvement of the medial frontal cortex in performance monitoring has been suggested, but little is known about neural processes that link performance monitoring to performance adjustment. Here, we recorded from neurons in the medial prefrontal cortex of monkeys learning arbitrary action-outcome contingencies. Some cells preferentially responded to positive visual feedback stimuli and others to negative feedback stimuli. The magnitude of responses to positive feedback stimuli decreased over the course of behavioral adaptation, in correlation with decreases in the amount of prediction error of action values. Therefore, these responses in medial prefrontal cells may signal the direction and amount of error in prediction of values of executed actions to specify the adjustment in subsequent action selections.     

RANKL-induced DC-STAMP is essential for osteoclastogenesis

Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Although receptor activator of nuclear factor-kappaB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the cell surface molecules involved in osteoclastogenesis are mostly unknown. Here, we report that the seven-transmembrane receptor-like molecule, dendritic cell-specific transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of DC-STAMP is rapidly induced in osteoclast precursor cells by RANKL and other osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small interfering RNAs and specific antibody markedly suppressed the formation of multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly induced the expression of the osteoclast marker tartrate-resistant acid phosphatase. These data demonstrate for the first time that DC-STAMP has an essential role in osteoclastogenesis.