Use of a Skin-Covering Pocket as a Local Flap and Negative Pressure Wound Therapy with Instillation and Dwell Time/Negative Pressure Wound Therapy for the Treatment of Diabetic Foot Ulcer with Calcaneal Osteomyelitis: A Case Report.

For diabetic foot ulcers with "pockets" (wound edge undermining), a surgical incision to the undermining space and debridement are required primarily. Osteomyelitis should be treated if present. Furthermore, it is necessary for the foot to be able to withstand load after controlling the infection and necrosis. We report a case of a patient treated with a skin-covering pocket as a local flap and negative pressure wound therapy with instillation and dwell time and negative pressure wound therapy to relieve osteomyelitis and promote wound contraction. There was no involvement of other body parts, and only the pocket consisting of skin at the sole of the foot was used, and load could be withstood.

Classification tree analysis to evaluate the most useful magnetic resonance image type in the differentiation between early and progressed hepatocellular carcinoma.

AIM: Using classification tree analysis, we evaluated the most useful magnetic resonance (MR) image type in the differentiation between early and progressed hepatocellular carcinoma (eHCC and pHCC). METHODS: We included pathologically proven 214 HCCs (28 eHCCs and 186 pHCCs) in 144 patients. The signal intensity of HCCs was assessed on in-phase (T1in) and opposed-phase T1-weighted images (T1op), ultrafast T2-weighted images (ufT2WI), fat-saturated T2-weighted images (fsT2WI), diffusion-weighted images (DWI), contrast enhanced T1-weighted images in the arterial phase (AP), portal venous phase (PVP), and the hepatobiliary phase. Fat content and washout were also evaluated. Fisher's exact test was performed to evaluate usefulness for the differentiation. Then, we chose MR images using binary logistic regression analysis and performed classification and regression tree analysis with them. Diagnostic performances of the classification tree were evaluated using a stratified 10-fold cross-validation method. RESULTS: T1in, ufT2WI, fsT2WI, DWI, AP, PVP, fat content, and washout were all useful for the differentiation (p < 0.05), and AP and T1in were finally chosen for creating classification trees (p < 0.05). AP appeared in the first node in the tree. The area under the curve, sensitivity and specificity for eHCC, and balanced accuracy of the classification tree were 0.83 (95% CI 0.74-0.91), 0.64 (18/28, 95% CI 0.46-0.82), 0.94 (174/186, 95% CI 0.90-0.97), and 0.79 (95% CI 0.70-0.87), respectively. CONCLUSIONS: AP is the most useful MR image type and T1in the second in the differentiation between eHCC and pHCC.

Cutaneous Angiokeratoma Treated With Surgical Excision and a 595-nm Pulsed Dye Laser.

Background. Angiokeratomas are vascular neoplasms with hyperkeratotic red to black papules and plaques, which may present as solitary or multiple lesions with variations in color, shape, and location. Successful treatment not only involves improvement of these symptoms but also cosmetic improvement. This report reviews 2 cases of cutaneous angiokeratoma treated with surgical excision and a 595-nm pulsed dye laser (PDL) in which the patients showed improvement of symptoms and cosmetic appearance. There are various types of angiokeratomas, and their extent, size, condition, and symptoms are different. Therefore, lesion-specific combined treatments may yield better results.

Surgical Management of Pachydermodactyly (PDD) via Midaxial Incision: A Case Report.

Pachydermodactyly (PDD), meaning "thick skin finger" in Greek, is a rare, noninflammatory, benign, superficial fibromatosis. We report the case of PDD in a 15-year-old boy who visited our clinic because of asymptomatic swelling of the proximal interphalangeal (PIP) joints on the third finger of both left and right hands. Physical examination revealed thickening of the skin in the radial and ulnar aspects of the PIP joints of his third finger of both hands without functional limitation or neurological symptoms. He had a habit of biting his swelling fingers, and he belonged to a basketball club at his junior high school. He had no medical history. Plain radiographs and magnetic resonance imaging of both hands showed only soft tissue thickening outside of the radial and ulnar collateral ligament of the bilateral third PIP joint. The lesions were suggestive of PDD. Surgical resection was performed via a midaxial incision and a Z-plasty to confirm the diagnosis and improve the aesthetic appearance of his hands. Histopathological examination of the lesions was compatible with PDD. After surgery on the left hand, the patient underwent the same surgery on the right hand. No recurrence or complications were observed at the one-year follow-up after surgical intervention. Thus, surgery for PDD via a midaxial incision may be a good treatment option for patients who wish to rectify the appearance of their digital deformity.

Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination - A Preclinical Study in Model Mice.

Amyloidogenic protein oligomers are thought to play an important role in the pathogenesis of neurodegenerative dementia, including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies. Previously we demonstrated that oral or intranasal rifampicin improved the cognition of APP-, tau-, and α-synuclein-transgenic mice by reducing the amount of Aß, tau, and α-synuclein oligomers in the brain. In the present study, to explore more effective and safer medications for dementia, we tested the drug combination of rifampicin and resveratrol, which is a multifunctional natural polyphenol with the potential to antagonize the adverse effects of rifampicin. The mixture was intranasally administered to APP-, tau-, and α-synuclein-transgenic mice, and their memory and oligomer-related pathologies were evaluated. Compared with rifampicin and resveratrol alone, the combinatorial medicine significantly improved mouse cognition, reduced amyloid oligomer accumulation, and recovered synaptophysin levels in the hippocampus. The plasma levels of liver enzymes, which reflect hepatic injury and normally increase by rifampicin treatment, remained normal by the combination treatment. Notably, resveratrol alone and the combinatorial medicine, but not rifampicin alone, enhanced the levels of brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, in the hippocampus. Furthermore, the combination showed a synergistic effect in ameliorating mouse cognition. These results show the advantages of this combinatorial medicine with regards to safety and effectiveness over single-drug rifampicin. Our findings may provide a feasible means for the prevention of neurodegenerative dementia that targets toxic oligomers.

Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers.

α-Synuclein oligomers are thought to play an important role in the pathogenesis of dementia with Lewy bodies (DLB). There is no effective cure for DLB at present. Previously, we demonstrated that in APP- and tau-transgenic mice, oral or intranasal rifampicin reduced brain Aß and tau oligomers and improved mouse cognition. In the present study, we expanded our research to DLB. Rifampicin was intranasally administered to 6-month-old A53T-mutant α-synuclein-transgenic mice at 0.1 mg/day for 1 month. The mice displayed memory impairment but no motor deficit at this age, indicating a suitable model of DLB. α-Synuclein pathologies were examined by the immunohistochemical/biochemical analyses of brain tissues. Cognitive function was evaluated by the Morris water maze test. Intranasal rifampicin significantly reduced the levels of [pSer129] α-synuclein in the hippocampus and α-synuclein oligomers in the visual cortex and hippocampus. The level of the presynaptic marker synaptophysin in the hippocampus was recovered to the level in non-transgenic littermates. In the Morris water maze, a significant improvement in spatial reference memory was observed in rifampicin-treated mice. Taken together with our previous findings, these results suggest that intranasal rifampicin is a promising remedy for the prevention of neurodegenerative dementia, including Alzheimer's disease, frontotemporal dementia, and DLB.

Optimal preoperative autologous blood storage volume required in surgeries for placenta previas and low-lying placentas.

AIM: The high rate of stored preoperative autologous blood wastage is concerning. This study analyzed patients who provided preoperative autologous blood donations (PABDs) for massive bleeding during surgery for placenta previas and low-lying placentas, and investigated the optimal PABD storage volume required to avoid allogeneic transfusion. METHODS: Of 386 patients who provided PABDs at our hospital from 2008 to 2013, 269 patients with placenta previas or low-lying placentas were retrospectively analyzed. The PABD storage volumes were stratified into four groups based on the amounts stored, and the allogeneic transfusion usage frequencies were compared. RESULTS: A total of 124 patients (46.1%) received PABDs and 12 patients (4.5%) received allogeneic transfusions. The average PABD volume wasted was 23 940 mL/year. The allogeneic transfusion utilization rate was significantly higher in the 1- to 300-mL group (17.2%) than in the 301- to 600-mL (1.69%), 601- to 900-mL (3.82%), and 901- to 1200-mL (0%) groups (P < 0.05). The PABD cut-off volume for avoiding allogeneic blood transfusion was 300 mL, and the odds ratio for ≤300-mL PABD in a multivariate analysis was 14.3 (95% confidence interval 1.3-149.3; P = 0.03). The maximum surgical blood order schedule was 2.16 units (432 mL), and the surgical blood order equation was 2.15 units (430 mL). CONCLUSION: The allogeneic transfusion utilization rate did not differ between the 600-mL group and the groups with higher PABD storage volumes; hence, storing 600 mL of PABD was appropriate for surgery for placenta previas and low-lying placentas.

Intranasal rifampicin for Alzheimer's disease prevention.

INTRODUCTION: Oral rifampicin has been shown to significantly reduce amyloid ß (Aß) and tau pathologies in mice. However, it shows occasional adverse effects such as liver injury in humans, making its use difficult for a long period. METHODS: To explore safer rifampicin treatment, APPOSK mice, a model of Alzheimer's disease, were treated with rifampicin for 1 month via oral, intranasal, and subcutaneous administration, and its therapeutic efficacy and safety were compared. RESULTS: Intranasal or subcutaneous administration of rifampicin improved memory more effectively than oral administration. The improvement of memory was accompanied with the reduction of neuropathologies, including Aß oligomer accumulation, tau abnormal phosphorylation, and synapse loss. Serum levels of a liver enzyme significantly rose only by oral administration. Pharmacokinetic study revealed that the level of rifampicin in the brain was highest with intranasal administration. DISCUSSION: Considering its easiness and noninvasiveness, intranasal administration would be the best way for long-term dosing of rifampicin.

Mutation-induced loss of APP function causes GABAergic depletion in recessive familial Alzheimer's disease: analysis of Osaka mutation-knockin mice.

The E693Δ (Osaka) mutation in APP is linked to familial Alzheimer's disease. While this mutation accelerates amyloid ß (Aß) oligomerization, only patient homozygotes suffer from dementia, implying that this mutation is recessive and causes loss-of-function of amyloid precursor protein (APP). To investigate the recessive trait, we generated a new mouse model by knocking-in the Osaka mutation into endogenous mouse APP. The produced homozygous, heterozygous, and non-knockin littermates were compared for memory, neuropathology, and synaptic plasticity. Homozygotes showed memory impairment at 4 months, whereas heterozygotes did not, even at 8 months. Immunohistochemical and biochemical analyses revealed that only homozygotes displayed intraneuronal accumulation of Aß oligomers at 8 months, followed by abnormal tau phosphorylation, synapse loss, glial activation, and neuron loss. These pathologies were not observed at younger ages, suggesting that a certain mechanism other than Aß accumulation underlies the memory disturbance at 4 months. For the electrophysiology studies at 4 months, high-frequency stimulation evoked long-term potentiation in all mice in the presence of picrotoxin, but in the absence of picrotoxin, such potentiation was observed only in homozygotes, suggesting their GABAergic deficit. In support of this, the levels of GABA-related proteins and the number of dentate GABAergic interneurons were decreased in 4-month-old homozygotes. Since APP has been shown to play a role in dentate GABAergic synapse formation, the observed GABAergic depletion is likely associated with an impairment of the APP function presumably caused by the Osaka mutation. Oral administration of diazepam to homozygotes from 6 months improved memory at 8 months, and furthermore, prevented Aß oligomer accumulation, indicating that GABAergic deficiency is a cause of memory impairment and also a driving force of Aß accumulation. Our findings suggest that the Osaka mutation causes loss of APP function, leading to GABAergic depletion and memory disorder when wild-type APP is absent, providing a mechanism of the recessive heredity.

Rifampicin is a candidate preventive medicine against amyloid-ß and tau oligomers.

Amyloid-ß, tau, and α-synuclein, or more specifically their soluble oligomers, are the aetiologic molecules in Alzheimer's disease, tauopathies, and α-synucleinopathies, respectively. These proteins have been shown to interact to accelerate each other's pathology. Clinical studies of amyloid-ß-targeting therapies in Alzheimer's disease have revealed that the treatments after disease onset have little benefit on patient cognition. These findings prompted us to explore a preventive medicine which is orally available, has few adverse effects, and is effective at reducing neurotoxic oligomers with a broad spectrum. We initially tested five candidate compounds: rifampicin, curcumin, epigallocatechin-3-gallate, myricetin, and scyllo-inositol, in cells expressing amyloid precursor protein (APP) with the Osaka (E693Δ) mutation, which promotes amyloid-ß oligomerization. Among these compounds, rifampicin, a well-known antibiotic, showed the strongest activities against the accumulation and toxicity (i.e. cytochrome c release from mitochondria) of intracellular amyloid-ß oligomers. Under cell-free conditions, rifampicin inhibited oligomer formation of amyloid-ß, tau, and α-synuclein, indicating its broad spectrum. The inhibitory effects of rifampicin against amyloid-ß and tau oligomers were evaluated in APPOSK mice (amyloid-ß oligomer model), Tg2576 mice (Alzheimer's disease model), and tau609 mice (tauopathy model). When orally administered to 17-month-old APPOSK mice at 0.5 and 1 mg/day for 1 month, rifampicin reduced the accumulation of amyloid-ß oligomers as well as tau hyperphosphorylation, synapse loss, and microglial activation in a dose-dependent manner. In the Morris water maze, rifampicin at 1 mg/day improved memory of the mice to a level similar to that in non-transgenic littermates. Rifampicin also inhibited cytochrome c release from the mitochondria and caspase 3 activation in the hippocampus. In 13-month-old Tg2576 mice, oral rifampicin at 0.5 mg/day for 1 month decreased amyloid-ß oligomer accumulation, tau hyperphosphorylation, synapse loss, and microglial activation, but not amyloid deposition. Rifampicin treatment to 14-15-month-old tau609 mice at 0.5 and 1 mg/day for 1 month also reduced tau oligomer accumulation, tau hyperphosphorylation, synapse loss, and microglial activation in a dose-dependent fashion, and improved the memory almost completely at 1 mg/day. In addition, rifampicin decreased the level of p62/sequestosome-1 in the brain without affecting the increased levels of LC3 (microtubule-associated protein light chain 3) conversion, suggesting the restoration of autophagy-lysosomal function. Considering its prescribed dose and safety in humans, these results indicate that rifampicin could be a promising, ready-to-use medicine for the prevention of Alzheimer's disease and other neurodegenerative diseases.

Vertical size disparity and the correction of stereo correspondence.

We examined the stage of vertical-disparity processing that produces a global stereoscopic slant. In two psychophysical experiments, we measured perceived slant about a vertical axis for two-dimensional stereoscopic patterns consisting of random dots, concentric lines, and radial lines. Binocular image differences were introduced into each pattern by vertically magnifying either the entire image for the right eye or that for the left eye. Because the continuous lines were geometrically ambiguous in local stereo correspondence, the three patterns differed from each other in the local horizontal disparity measured in retinal coordinates. The two experiments revealed that, despite the differences in the retinal horizontal disparity, the slant settings were generally similar for the three patterns, in both short and long viewing distances (25 cm and 120 cm, respectively). These results are consistent with the idea that the visual system uses vertical disparity at least when establishing local stereo correspondence. A Bayesian model is proposed to account for the results.

A supramolecular DNA self-assembly based on ß-cyclodextrin-adamantane complexation as a bioorthogonal sticky end motif.

We propose linear end-to-end assemblies of short DNA duplexes based on ß-cyclodextrin-adamantane complexation. The assembled duplexes exhibited increased Tm values compared with those of the corresponding natural hybrids. Competition experiments with external guest molecules showed a substantial decrease in Tm of the terminal modified duplexes, suggesting the viability of inter-duplex complexation.