Association of Balance Impairment with Risk of Incident Dementia among Older Adults.

BACKGROUND: A growing body of data suggests that balance impairment may be linked to the onset of dementia. OBJECTIVES: However, a large-scale epidemiologic investigation is needed to clarify its association in older adults. DESIGN: A retrospective-prospective hybrid database. SETTING: Cox proportional hazards regression model was used to assess the relationship between balance impairment and the risk of incident dementia, and the results were provided as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). All participants were tracked until the date of incident dementia, death, or 31 December 2019 whichever came first. PARTICIPANTS: We analyzed 143,788 older adults who had at least one health screening between 2009 and 2019 from the Korea National Health Insurance Service-Senior Cohort. MEASUREMENTS: A total of 3,774 cases of dementia were discovered throughout 850,425 person-years of follow-up investigation. Balance impairment was associated with a risk of dementia compared to those without balance impairment (adjusted hazard ratio [aHR] 1.83; 95% CI, 1.69-2.00; P value <0.001). RESULTS: Risks of the Alzheimer's disease (aHR, 1.80; 95% CI, 1.65-1.96; P for trend <0.001) and the vascular dementia (aHR, 2.94; 95% CI, 1.89-4.58; P for trend <0.001) showed comparable trends and findings. CONCLUSIONS: Balance impairment was found to be independently associated with an increased risk of dementia in older adults.

Hepatitis A virus strains identified in jogaejeot associated with outbreaks in Seoul, South Korea.

Jogaejeot, seasoned Venerupis philippinarum, is a traditional Korean fermented food, and hepatitis A virus (HAV) can be transmitted through contaminated food, especially bivalve shellfish, causing acute gastroenteritis worldwide. Here, we carried out a phylogenetic analysis to identify and characterize HAV strains in jogaejeot samples associated with hepatitis A (HA) outbreaks in Seoul, South Korea, in 2019. The HAV strains were identified using blast and molecular analysis of the amplified HAV VP1-P2B genome region. The HAV strains identified in the five jogaejeot samples shared at least 99% sequence identity, were all classified as genotype IA and were most closely related to strains that are widespread in East Asia. These results support a link between the consumption of jogaejeot and the HA outbreaks observed in 2019 in Seoul. In addition, they indicate a need for more stringent enforcement of food safety regulations for the shellfish industry, especially against HAV, and the value of widespread vaccination.

Cytopathic changes and pro-inflammatory cytokines induced by Naegleria fowleri trophozoites in rat microglial cells and protective effects of an anti-Nfa1 antibody.

Naegleria fowleri, a free-living amoeba, causes fatal primary amoebic meningoencephalitis in experimental animals and humans. The nfa1 gene (360 bp) was previously cloned from a cDNA library of pathogenic N. fowleri by immunoscreening, and produced a 13.1-kDa recombinant protein that showed pseudopodia-specific localization by immunocytochemistry. On the basis of an idea that the pseudopodia-specific Nfa1 protein seems to be involved in the pathogenicity of N. fowleri, the cytopathic activity of N. fowleri trophozoites co-cultured with rat microglial cells was observed, and the effects of an anti-Nfa1 antibody in a co-culture system were elucidated. Using light, scanning and transmission electron microscopy, it was seen that N. fowleri trophozoites in contact with microglial cells produced vigorous pseudopodia and a food-cup structure. Microglial cells were destroyed by N. fowleri trophozoites as seen from necrotic cell death in a time-dependent manner. In a(51)Cr release assay, N. fowleri showed 17.8%, 24.9%, 54.6% and 98% cytotoxicity against microglial cells at 3, 6, 12 and 24 h post-incubation, respectively. However, when anti-Nfa1 antibody was added in a coculture system, N. fowleri cytotoxicity was reduced to 15.5%, 20.3%, 46.7% and 66.9%, respectively. Moreover, microglial cells co-cultured with N. fowleri trophozoites secreted the pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. In the presence of anti-Nfa1 antibody, the secretion of TNF-alpha was slightly, but not significantly, decreased.

A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study.

HLA-matched UC blood-derived multipotent stem cells were directly transplanted into the injured spinal cord site of a 37-year-old female patient suffering from spinal cord injury (SPI). In this case, human cord blood (UCB)-derived multipotent stem cells improved sensory perception and movement in the SPI patient's hips and thighs within 41 days of cell transplantation. CT and MRI results also showed regeneration of the spinal cord at the injured site and some of the cauda equina below it. Therefore, it is suggested that UCB multipotent stem cell transplantation could be a good treatment method for SPI patients.

Fine-needle aspiration cytology of pleuropulmonary blastoma: a case report with unusual features.

Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm of childhood, typically presenting as a pulmonary and/or pleural-based mass with cystic, solid, or combined features. Histologically, the tumor is well characterized with a mixture of primitive mesenchymal and variably differentiated sarcomatous components, and the cytologic features described in the three previous reports are also compatible to the histologic ones. Now, we present another case of PPB showing unusual features. A 3-yr-old boy presented with a pleural- or chest wall-based tumor. The fine-needle aspiration cytologic smears were highly cellular with poorly differentiated cells showing variable size and shape rather than those of typical blastemal cells. The histologic findings were also distinctive, exhibiting diffuse sheets of poorly differentiated cells without typical blastemal cell component. Diagnosis was confirmed by the support of immunohistochemical and ultrastructural features. The patient underwent a typical aggressive clinical course to death within 8 mo after diagnosis.

Impairments of learning and memory following intracerebroventricular administration of AF64A in rats.

Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform from 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th day, but not 8th day. In the active avoidance for the pre-trained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for spatial cognition.

Cytologic and histologic correlation of atypical glandular cells of undetermined significance.

To determine the cytologic and histologic correlation of atypical glandular cells of undetermined significance (AGUS) in Papanicolaou smears, a cytology file from January 1998 to May 1999 was reviewed. Surgical pathology files were searched to determine which patients received subsequent biopsies. One hundred thirty-two patients with AGUS were identified. Corresponding biopsies were available for 82 of these cases. AGUS has been sub-classified into 3 subtypes: 1) AGUS, favor reactive; 2) AGUS, not otherwise specified; and 3) AGUS, favor neoplasia. The pathologic findings for the respective Papanicolaou smears with the diagnosis of each subtype of AGUS through the follow-up period were as follows: benign lesions in 56.1%, 0%, and 1.2%; squamous intraepithelial lesions 2.4%, 0%, and 1.2%; glandular intraepithelial lesions 0%, 0%, and 17.1%; endometrial simple hyperplasia 1.2%, 0%, and 0%; and carcinoma 0%, 9.8%, and 11%, respectively. In conclusion, AGUS, on cervical cytologic screening, was correlated with significant pathologic findings in 41.5% of the patients (37.8% with preinvasive or invasive glandular lesions and 9.6% with combined squamous intraepithelial lesions). It is thought that intensive follow-up studies, including colposcopy, cervical biopsy, and curettage, should be recommended for complete evaluation of AGUS.

Presacral epidermoid cyst: imaging findings with histopathologic correlation.

BACKGROUND: The aim of this study was to determine the imaging characteristics of presacral epidermoid cysts and correlate the imaging findings with the histopathologic findings. METHODS: We retrospectively reviewed sonographic, computed tomographic, and magnetic resonance examinations in four consecutive patients with a pathologically proven presacral epidermoid cyst. Imaging findings of the presacral epidermoid cyst were correlated with the histopathologic findings. RESULTS: In all four patients, sonography showed a presacral mass with a heterogeneous low echogenicity, and computed tomography showed a discrete well-defined hypodense presacral mass with a thin wall. In the three patients who underwent magnetic resonance imaging, the mass showed a heterogeneous low signal intensity on the T1-weighted image and a high signal intensity with multiple small foci of low signal intensity in the nondependent portion of the mass on the T2-weighted image. These imaging findings correlated well with the pathologic results. Aggregates of keratinous material contributed to these imaging findings. CONCLUSION: In the diagnosis of the presacral epidermoid cyst, sonographic and magnetic resonance imaging findings may be helpful.

A neural network for 500 word vocabulary word spotting using non-uniform units.

We introduce acoustic sub-word units to neural networks for speaker-independent continuous speech recognition. The functions of segmenting input and detecting words are implemented with networks of simple structures. The non-uniform unit which we introduce in this research can model phoneme variations caused by co-articulation spread over several phonemes and between words. These units can be segmented by the network according to stationary and transition parts of speech without iteration or without considering all possible position shifts. A word lexicon can be trained by the network, which can effectively memorize all transcription variations in the training utterances of words. The results of speaker-independent word spotting of 520 words with TIMIT data are described.

Expression of cyclin-dependent kinase inhibitor p27kip1 in malignant lymphomas.

p27kip1 is a cyclin-dependent kinase inhibitor that regulates progression from G1 into S phase. Aberrations in cell cycle control are often observed in tumors and might even be necessary in tumor development. Recent reports showed that low p27kip1 expression is associated with poor prognosis in several tumors and leukemia. To investigate the expression of p27kip1 in malignant lymphomas and elucidate the role of p27kip1 as a possible prognostic indicator, the authors performed an immunohistochemical staining of p27kip1 correlated with Ki-67 labelling index and clinical parameters. p27kip1 expression was reduced variably in most malignant lymphomas and inversely correlated with Ki-67 labelling index (p=0.0151). Regarding chemotherapeutic response, p271kip1 expression in the complete remission group showed statistically significant difference in expression compared to the progressive disease group (p=0.0021). There were significant differences in survival between cases with low and high p27kip1 expression (p=0.0071). In a multivariate Cox analysis, p27kip1 expression was independent prognostic factors as well as other known prognostic factors including age, grade, stage and chemotherapeutic response. In conclusion, the study suggests that reduced expression of p27kip1 protein may play a role in the pathogenesis and biologically aggressive behavior of malignant lymphomas.

Chronic tuberculous epididymitis: color Doppler US findings with histopathologic correlation.

BACKGROUND: The aim of this study was to determine the color Doppler features of tuberculous epididymitis and to correlate these findings with histopathologic findings. METHODS: Color Doppler ultrasound (US) findings of 12 histopathologically proven tuberculous epididymitis and tuberculous epididymo-orchitis in 11 consecutive patients were retrospectively analyzed. Color Doppler US findings of tuberculous epididymitis were correlated with histopathologic findings. RESULTS: Color Doppler US findings of tuberculous epididymitis demonstrated no blood flow in the epididymal lesions except for focal linear or spotty flow signals in the peripheral portion. These findings correlated well with pathologic findings; the central portion of the epididymal lesions demonstrated granulomas with caseation necrosis, and the peripheral portion of the epididymal lesions had several medium to small vessels. CONCLUSIONS: Color Doppler US may be helpful for differential diagnosis of tuberculous epididymitis and non-tuberculous epididymitis.

Lung metastases manifesting as pulmonary infarction by mucin and tumor embolization: radiographic, high-resolution CT, and pathologic findings.

We present a case of lung metastasis manifesting as lung infarction by mucin and tumor embolization. The radiograph and high-resolution CT showed multiple focal consolidations with ground glass attenuation in subpleural areas of both lungs. Diagnosis was made by open lung biopsy, which revealed pulmonary infarction caused by intravascular adenocarcinoma with numerous mucus emboli in pulmonary arteries. Subpleurally located consolidations on high-resolution CT correlated well with the histologic findings of lung infarction by mucin and tumor emboli.

Primary hepatic carcinoid tumor with a paranuclear clear zone: a case report.

Carcinoid tumors having distinct paranuclear clear zones seen on hematoxylin and eosin stain are rare and few cases have been reported in the literature. Furthermore, primary hepatic carcinoid tumor with a paranuclear clear zone is extremely rare. We recently experienced a case from a 48-year-old man who presented a large single mass, 12 cm in largest diameter, in the right lobe of the liver. Histologically, the tumor revealed characteristic organoid pattern with central hyaline degeneration. The tumor cells had a prominent paranuclear vacuolated dear zone. On immunohistochemistry, tumor cells were diffusely positive for synaptophysin and focally stained for chromogranin A. Ultrastructural examination revealed paranuclear aggregation of intermediate filaments and membrane-bound clear vesicles, which corresponded to the paranuclear vacuolated clear zone.

Bcl-2 and p53 expressions in invasive bladder cancers.

We investigated the Bcl-2 and P53 protein expressions in 89 patients with bladder cancers using immunohistochemical analysis. In superficial tumors, the times of tumor recurrence and progression were significantly shorter in the P53-positive group than in the negative group (p < 0.005, p < 0.05, respectively). In invasive tumors, the disease-specific actuarial survivals were significantly lower in the P53 and Bcl-2-positive groups (p <0.05, p < 0.025, respectively). In multivariate analysis, overexpression of p53 and Bcl-2 had independent prognostic value for survivals in invasive tumor, while disease-free survival was related independently to overexpression of p53 in superficial tumor. The results of our assessment for chemoeffectiveness revealed that the patients with Bcl-2-positive tumors had significantly lower response rates than those with Bcl-2-negative tumors (p < 0.05). We conclude that p53 expression is an independent, poor prognostic marker in invasive tumors as well as in superficial tumors and that overexpression of Bcl-2 is independently associated with a reduced-survival in patients with invasive tumors. These prognostic differences related to P53 and Bcl-2 expression in invasive bladder cancers may be partly due to chemo- or radio-sensitivity in relation to apoptotic process.

Retroviral transfer of a human beta-globin/delta-globin hybrid gene linked to beta locus control region hypersensitive site 2 aimed at the gene therapy of sickle cell disease.

Human gamma-globin and delta-globin chains have been previously identified as strong inhibitors of the polymerization of hemoglobin S, in contrast to the beta-globin chain, which exerts only a moderate antisickling effect. However, gamma-globin and delta-globin are normally expressed at very low levels in adult erythroid cells, in contrast to beta-globin. We report the design of a beta-globin/delta-globin hybrid gene, beta/delta-sickle cell inhibitor 1 (beta/delta-SCI1) and its transduction by retrovirus-mediated gene transfer. The beta/delta-SCI1-encoding gene retains the overall structure of the human beta-globin gene, while incorporating specific amino acid residues from the delta chain previously found responsible for its enhanced antisickling properties. To achieve high expression levels of beta/delta-SCI1 in adult erythrocytes, the hybrid gene was placed under the transcriptional control of the human beta-globin promoter and the DNase I hypersensitive site 2 of the human beta locus control region. High-titer retroviruses were generated, and stable proviral transmission was achieved in infected cells. The mRNA expression levels of the beta/delta-SCI1 gene in infected, dimethyl sulfoxide-induced murine erythroleukemia cells approached 85% of the endogenous murine beta maj-globin mRNA, on a per gene basis, evidence that high gene expression levels were achieved in adult erythroid cells. Further evaluation of this strategy in transgenic animal models of sickle cell disease should assess its efficacy for the gene therapy of human patients.

Mutagenesis of retroviral vectors transducing human beta-globin gene and beta-globin locus control region derivatives results in stable transmission of an active transcriptional structure.

Retrovirus-mediated gene transfer of the human beta-globin gene into hematopoietic stem cells is an attractive approach to the therapy of human beta-globin gene disorders. However, expression of the transduced beta-globin gene linked to its proximal cis-acting sequences (-0.8 to +0.3 kb from the cap site) is considerably below the level required for a significant therapeutic effect. The discovery of the beta-locus control region (beta-LCR), organized in four major DNase I hypersensitive sites far upstream of the human beta-like globin gene cluster, provided a potential means to achieve a high level of expression of a linked human beta-globin gene, but initial attempts to incorporate beta-LCR derivatives in retroviral vectors resulted in the production of low-titer viruses with multiple rearrangements of the transmitted proviral structures. We now describe how extensive mutagenesis of the transduced beta-globin gene, eliminating a 372 bp intronic segment and multiple reverse polyadenylation and splicing signals, increases viral titer significantly and restores stability of proviral transmission upon infection of cell lines and bone marrow-repopulating cells. These optimized vectors have enabled us to analyze the expression properties of various retrovirally transduced beta-LCR derivatives in dimethylsulfoxide-induced murine erythroleukemia cells and to achieve ratios of human beta-globin/murine beta maj-globin mRNA, on a per gene basis, as high as 80%.

An improved palpebral spring for the management of paralytic lagophthalmos.

Facial nerve paralysis with orbicularis muscle palsy can result in serious corneal complications, such as exposure, ulceration, and perforation. Eyelid springs have been used for patients with orbicularis muscle palsy to provide corneal protection while maintaining vision by restoring some kinetic eyelid function. The authors report on 24 patients with facial nerve paralysis who underwent implantation of an eyelid spring over a period of 8 years. The most common cause of orbicularis muscle paralysis was acoustic neuroma, followed by squamous cell carcinoma. Eighty-three percent of the cases successfully regained and maintained their eyelid function during the follow-up period, averaging 3.0 years. We have modified the spring to allow permanent attachment to the orbital rim by wiring. This modification of the surgical technique has minimized the most common postoperative complication: loosening of the spring from its periosteal attachment with subsequent loss of function and extrusion. In addition, transcutaneous adjustments of the spring now can be made without an incision using clasp-adjusting dental pliers. In selected patients, the placement of an eyelid spring prevents the corneal complications associated with paralytic lagophthalmos while maintaining visual function.