The Physical Resilience Instrument for Older Adults (PRIFOR) in Surgical Inpatients: Further Evidence for Its Factor Structure and Validity.

BACKGROUND: The Physical Resilience Instrument for Older Adults (PRIFOR) is a questionnaire for assessing physical resilience in older adults suffering from acute health stressors. Prior psychometric evidence of the PRIFOR showed that it has good criterion-related validity, known-group validity, predictive validity, and internal consistency. However, it is unclear whether the PRIFOR can be replicated in older adults suffering after surgical treatment. OBJECTIVES: This study aimed at evaluating whether the three-factor structure of the PRIFOR can be replicated in older adults suffering after surgical treatment. Moreover, the concurrent validity of the PRIFOR was examined using the association between the PRIFOR and measures of depression, cognition, activities of daily living, and frailty. DESIGN AND SETTING: A longitudinal study was adopted in a tertiary-care medical center in Taiwan. PARTICIPANTS: A total of 207 patients aged 65 years old and older who underwent surgery and if they were able to communicate independently. MEASUREMENTS: The PRIFOR, the 5-item Geriatric Depression Scale, the Short Portable Mental Status Questionnaire, the Katz Index of Independence in Activities of Daily Living and Clinical Frailty Scale were all assessed after surgery. RESULTS: The three-factor structure (positive thinking, cope and adjust lifestyle, and belief and hopeful mindset) was supported by the CFA results in the present sample. In addition, the PRIFOR showed good concurrent validity with depression (r = -0.470 to -0.542), cognition (r = 0.358 to 0.409), activities of daily living (r = 0.209 to 0.310), and frailty (r =-0.161 to -0.237). CONCLUSION: The PRIFOR can be recommended to measure physical resilience in older adults suffering after surgical treatment. For the adequate estimation of older adults' level of physical resilience postoperatively and to guide the implementation of individualized interventions, it is important to provide appropriate care for older adults to recover after surgery.

New approach to establish an object reference frame for dental arch in computer-aided surgical simulation.

The purpose of this study was to develop a principal component analysis-based adaptive minimum Euclidean distances (PAMED) approach to establish an optimal object reference frame for symmetrical alignment of the dental arch during computer-aided surgical simulation (CASS). It was compared with our triangular methods and the standard principal component analysis (PCA) method. Thirty sets of maxillary digital models were used. Midsagittal and occlusal planes were ranked by three experienced evaluators based on their clinical judgment. The results showed that for the midsagittal plane, all three evaluators ranked "ideal" for all 30 models with the PAMED method, 28 with the triangular method, and at least 11 with the PCA method. For the occlusal plane, one evaluator ranked all 30 models "ideal" with both the PAMED and the PCA methods while the other two evaluators ranked all 30 models "ideal" with the triangular method. However, the differences among the three methods were minimal. In conclusion, our PAMED method is the most reliable and consistent approach for establishing the object reference frame for the dental arch in orthognathic surgical planning. The triangular method should be used with caution because it can be affected by dental arch asymmetry. The standard PCA method is not recommended.

Successful Management of New-Onset Diabetes Mellitus and Obesity With the Use of Laparoscopic Sleeve Gastrectomy After Kidney Transplantation-A Case Report.

In kidney transplantation, obesity is associated with poorer graft survival and patient survival. Bariatric surgery may provide benefit for these patients, not only by inducing weight loss, but also via reduction of diabetes. We report a case of morbid obesity, poorly controlled new-onset diabetes mellitus, and gout after kidney transplantation that was treated with laparoscopic sleeve gastrectomy 3 years after kidney transplantation. After 1 year of follow-up, 76% excessive body weight loss was attained. No complications were noted. The operation also provided total remission of diabetes and gout as well as good graft survival. Based on our experience, laparoscopic sleeve gastrectomy may be a feasible treatment for obese patients after renal transplantation to help resolve obesity and control new-onset diabetes. However, the timing of operation and the long-term potential for graft and patient survivals with this operation require further study.

Promising antimicrobial capability of thin film metallic glasses.

Thin film metallic glasses (TFMGs) are demonstrated to exhibit excellent surface flatness, high corrosion resistance and satisfactory hydrophobic properties. Moreover, the antimicrobial and biocompatibility abilities of TFMGs are examined and the results are compared with the behavior of pure Ag and 316L stainless steel. Three TFMGs, Al48Ag37Ti15, Zr54Ti35Si11, and Zr59Ti22Ag19, are prepared by sputtering to assess the antimicrobial performance against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, which are the most common nosocomial infection pathogens. Experimental results show that the antimicrobial effect of the Al- or Ag-containing AlAgTi and ZrTiAg TFMGs is similar to that of the pure Ag coating. The ZrTiSi TFMG with no Ag or Al shows poor antimicrobial capability. The physical properties of highly smooth surface and hydrophobic nature alone are not sufficient to result in promising antimicrobial ability. The chemical metal ion release still plays a major role, which should be born in mind in designing biomedical devices.

Three-dimensional analysis of the surface registration accuracy of electromagnetic navigation systems in live endoscopic sinus surgery.

BACKGROUND: Studies on the performance of surface registration with electromagnetic tracking systems are lacking in both live surgery and the laboratory setting. This study presents the efficiency in time of the system preparation as well as the navigational accuracy of surface registration using electromagnetic tracking systems. METHODOLOGY: Forty patients with bilateral chronic paranasal pansinusitis underwent endoscopic sinus surgery after undergoing sinus computed tomography scans. The surgeries were performed under electromagnetic navigation guidance after the surface registration had been carried out on all of the patients. The intraoperative measurements indicate the time taken for equipment set-up, surface registration and surgical procedure, as well as the degree of navigation error along 3 axes. RESULTS: The time taken for equipment set-up, surface registration and the surgical procedure was 179 +- 23 seconds, 39 +- 4.8 seconds and 114 +- 36 minutes, respectively. A comparison of the navigation error along the 3 axes showed that the deviation in the medial-lateral direction was significantly less than that in the anterior-posterior and cranial-caudal directions. CONCLUSION: The procedures of equipment set-up and surface registration in electromagnetic navigation tracking are efficient, convenient and easy to manipulate. The system accuracy is within the acceptable ranges, especially on the medial-lateral axis.

Perimenopause and incidence of depression in midlife women: a population-based study in Taiwan.

AIM: To examine the relationships between depressive symptoms, menopausal status, and menopausal symptoms in middle-aged women. MATERIAL AND METHODS: This cross-sectional, population-based study involved patients in the Taiwanese community. Data were retrieved from the nationwide 2002 Health Promotion Knowledge, Attitude, and Performance Survey in Taiwan. We assessed depressive symptoms using the Taiwanese Depression Questionnaire with a cut-off point of 18 of 19. Self-reported perception of menopausal status, frequency of menstrual periods in the preceding 12 months, and a history of oophorectomy surgery were used to categorize the women's menopausal status into premenopause, perimenopause, postmenopause, and surgical menopause. RESULTS: A total of 3359 women aged 40-55 years were selected. Among these patients, 145 women (4.7%) experienced higher levels of concurrent depressive symptoms. The increase in depressive symptoms was significantly associated with menopausal status and most of the menopausal symptoms. After controlling for age, marital status, education, income, smoking, hormone therapy, and menopause symptoms, multivariate logistic regression showed that perimenopause was still significantly associated with depression in midlife women (odds ratio 1.97; 95% confidence interval 1.24-3.14). CONCLUSION: Independent of menopausal symptoms, perimenopausal status increases the risk of depression.

Targeted endostatin-cytosine deaminase fusion gene therapy plus 5-fluorocytosine suppresses ovarian tumor growth.

There are currently no effective therapies for cancer patients with advanced ovarian cancer, therefore developing an efficient and safe strategy is urgent. To ensure cancer-specific targeting, efficient delivery, and efficacy, we developed an ovarian cancer-specific construct (Survivin-VISA-hEndoyCD) composed of the cancer specific promoter survivin in a transgene amplification vector (VISA; VP16-GAL4-WPRE integrated systemic amplifier) to express a secreted human endostatin-yeast cytosine deaminase fusion protein (hEndoyCD) for advanced ovarian cancer treatment. hEndoyCD contains an endostatin domain that has tumor-targeting ability for anti-angiogenesis and a cytosine deaminase domain that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic drug, 5-fluorouracil. Survivin-VISA-hEndoyCD was found to be highly specific, selectively express secreted hEndoyCD from ovarian cancer cells, and induce cancer-cell killing in vitro and in vivo in the presence of 5-FC without affecting normal cells. In addition, Survivin-VISA-hEndoyCD plus 5-FC showed strong synergistic effects in combination with cisplatin in ovarian cancer cell lines. Intraperitoneal (i.p.) treatment with Survivin-VISA-hEndoyCD coupled with liposome attenuated tumor growth and prolonged survival in mice bearing advanced ovarian tumors. Importantly, there was virtually no severe toxicity when hEndoyCD is expressed by Survivin-VISA plus 5-FC compared with CMV plus 5-FC. Thus, the current study demonstrates an effective cancer-targeted gene therapy that is worthy of development in clinical trials for treating advanced ovarian cancer.

Non-typhoidal Salmonella bacteraemia in elderly patients: an increased risk for endovascular infections, osteomyelitis and mortality.

Non-typhoidal Salmonella (NTS) is a common pathogen causing foodborne infections, bacteraemia, and extra-intestinal focal infections (EFIs) in humans. The study compares the clinical characteristics of elderly patients with NTS bacteraemia with those of young adults. Of 272 adults with NTS bacteraemia identified in this study, 162 (59·6%) were aged ⩾55 years. EFIs were observed in 36% of the 162 patients. The most common EFIs in the elderly patients (⩾55 years) was mycotic aneurysm, followed by pulmonary infections and bone/joint infections. Elderly patients more often had chronic heart, lung, renal and malignant diseases, had more EFIs, and a higher 30-day mortality rate. Independent factors of 30-day mortality in elderly patients were solid-organ tumour [adjusted odds ratio (aOR) 4·4, P=0·003], mycotic aneurysm (aOR 3·7, P=0·023) and shock (aOR 12·1, P<0·0001). HIV infection, autoimmune diseases, and receipt of immunosuppressive therapy were more often observed in young patients.

Use of RNA interference to modulate liver adenoma development in a murine model transgenic for hepatitis B virus.

Chronic hepatitis B virus (HBV) infection is closely related to the development of severe liver complications, including hepatocellular carcinoma. In previous studies, we reported that in vivo long-term HBV suppression in transgenic mice can be achieved without apparent toxicity by short hairpin RNA sequentially delivered using adeno-associated viral (AAV) vectors of different serotypes. Our goal herein was to address the clinical utility of this delivery system and, in particular, to determine whether RNA interference (RNAi) and its ability to induce long-term HBV suppression will modulate the development of HBV-associated liver pathology. As a model system, we used a unique HBV transgenic mouse model, containing a 1.3 times over length of the HBV genome, on the ICR mouse background. These transgenic mice produce high serum HBV titers comparable with human chronic HBV patients, and, importantly, manifest characteristic HBV-associated pathology, including progressive hepatocellular injury and the development of hepatocellular adenoma. Using this system, we injected animals with AAV vectors expressing either HBV-specific or a control luciferase-specific short hairpin RNA and followed animals for a total of 18 months. We report herein that AAV-mediated RNAi therapy profoundly inhibits HBV replication and gene expression, with a significant reduction in hepatic regeneration, liver enzymes and, importantly, the appearance of liver adenomas. Indeed, the therapeutic effect of RNAi correlated with the reduction in HBV titers. Our data demonstrate that appropriately designed RNAi therapy has the potential to prevent formation of HBV-associated hepatocellular adenoma.

Correlates of anti-EBV EBNA1 IgA positivity among unaffected relatives from nasopharyngeal carcinoma multiplex families.

BACKGROUND: To determine whether non-viral nasopharyngeal carcinoma (NPC) risk factors might be associated with (and mediated through) Epstein-Barr virus (EBV) serological responses linked to NPC risk, we evaluated predictors of risk of anti-EBNA1 IgA seropositivity and other markers among unaffected relatives from a large NPC family study in Taiwan. METHODS: Multivariate logistic regression conditioned on family was used to examine the associations between sociodemographic, dietary, lifestyle, and occupational variables and risk of anti-EBV EBNA1 IgA positivity, anti-VCA IgA, and anti-DNase positivity. RESULTS: Among 2393 unaffected relatives from 319 multiplex families, 1180 (49.3%) were anti-EBV EBNA1 IgA seropositive. None of the associations with anti-EBNA1 IgA were statistically significant, except for being 31-50 years of age (vs <30, adjusted ORs 0.51-0.57). For one or more EBV serological markers, there were suggestive associations for older age, GuangDong firm salted fish, betel use, current alcohol use, and male gender. CONCLUSION: Overall, we found little evidence to suggest that non-viral NPC risk factors significantly alter EBV serological patterns, suggesting that non-viral NPC risk factors act through pathways independent of EBV serological responses.

Synovial chondrosarcoma arising from synovial chondromatosis of the knee.

We report the case of a 51-year-old woman who had suffered from right knee pain and stiffness for 40 years. Her symptoms had gradually worsened over the past 5 years. One year previously, when she first visited our clinic, plain radiographs and CT scan images had revealed synovial chondromatosis over the right knee. At the current admission, follow-up MRI showed synovial masses around the knee and worsening of endosteal cortical scalloping in the patella, femoral condyle, and tibial plateau. After diagnosis on the basis of frozen sections, the patient had total excision of the lesions and total knee athroplasty. Histological examination revealed synovial chondromatosis in the joint cavity and grade 1 chondrosarcoma invasion into the adjacent bone. In long-standing synovial chondromatosis, presentation with aggravated symptoms and deterioration on imaging findings should alert clinicians to the potential for malignant change.

Anti-N-methyl-D-aspartate receptor encephalitis in a young woman with an ovarian tumour.

Anti-N-methyl-D-aspartate receptor encephalitis is characterised by psychiatric and neurological abnormalities and occurs in frequent association with ovarian teratoma. We report the first confirmed case of teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis in Hong Kong in a young woman presenting with confusion and prominent dyskinesia, followed by a review of the current literature.

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-delta.

Earlier, we showed that epidermal growth factor receptor (EGFR) signaling in human glioma cells increased cyclooxygenase-2 (COX-2) expression through p38-mitogen-activated protein kinase (MAPK)-dependent activation of the Sp family of transcription factors. Further mechanistic details of EGFR-dependent induction of COX-2 expression in glioma cells remained elusive. Protein kinase Cs (PKCs) comprise a family of serine-threonine kinases that are major mediators of signaling from receptor tyrosine kinases. Here, we report that PKC-delta, a novel PKC isoform, plays a role in EGF-dependent COX-2 induction in human glioma cells. Pharmacological inhibition and genetic silencing (through siRNA or dominant-negative expression) of PKC-delta confirm a role for this PKC isoform in EGF-dependent COX-2 induction. Overexpression of a functional PKC-delta enhanced COX-2 expression indicating that PKC-delta is not only necessary but also sufficient to regulate COX-2 levels. Inhibition of p38-MAPK pharmacologically or with siRNA further shows that p38-MAPK is required for activation of PKC-delta by EGF while inhibition of PKC-delta had no discernible effects on p38-MAPK activation. Finally, EGF stimulation promotes physical interactions between PKC-delta and Sp1 resulting in phosphorylation and nuclear localization of this transcription factor. These data provide the first evidence that PKC-delta is a critical link between p38-MAPK and Sp1-dependent COX-2 expression in human glioma cells.

Community-acquired Klebsiella pneumoniae complicated skin and soft-tissue infections of extremities: emphasis on cirrhotic patients and gas formation.

BACKGROUND: Klebsiella pneumoniae was rarely reported to cause complicated skin and soft tissue infections (cSSTIs). Our study was to delineate clinical characteristics and outcome of cSSTIs involving extremities caused by K. pneumoniae. PATIENTS AND METHODS: Adult patients aged 16 years or more with community-acquired cSSTIs, which involved the extremities and were caused by four common aerobic pathogens at a medical center in southern Taiwan during a 54-month period, were reviewed. RESULTS: Of 76 cases enrolled, Staphylococcus aureus was the most common pathogen (52 cases, 68%), followed by K. pneumoniae (16, 21%), beta-hemolytic streptococci (5, 7%), and Escherichia coli (3, 4%). Forty-six (61%) had underlying conditions, and diabetes mellitus was most common among K. pneumoniae and non-K. pneumoniae groups (63% and 45%, respectively). Compared to patients with cSSTIs caused by other bacteria, those with K. pneumoniae cSSTIs were predominantly male, more often had liver cirrhosis, malignant neoplasm and alcoholism. In addition, they were more likely to have fever, shock, bacteremia, gas formation, pyomyositis, metastatic infections, as well as longer durations of hospitalization. Using multivariate analysis, liver cirrhosis (adjusted odds ratio [aOR] 12.5, 95% confidence interval [CI] 2.0-79.1, p = 0.007) and male gender (aOR 11.5, 95% CI 1.1-116.8, p = 0.039) were significantly associated with K. pneumoniae cSSTIs. CONCLUSIONS: We highlight the role of K. pneumoniae in Taiwanese patients with cSSTIs involving extremities, and its potential for gas and pus formation, and metastatic infections. Empiric antimicrobial coverage of K. pneumoniae and close monitoring of metastatic infections are mandatory for patients with risk factors.

Administration of 5-androstenediol to mice: pharmacokinetics and cytokine gene expression.

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in military and civilian populations associated with possible exposure to ionizing radiation. Previous studies in mice have shown that a single subcutaneous (sc) injection of the natural steroid androst-5-ene-3beta,17beta-diol (5-androstenediol, 5-AED), 24-48 h prior to a lethal dose of whole-body (60)Co gamma radiation, stimulated hematopoiesis and enhanced survival. These effects are consistent with our previous observation of 5-AED-induced elevations in circulating G-CSF in normal and irradiated mice. The purpose of this study was to obtain data on the pharmacokinetics of 5-AED after sc and buccal administration to mice, and to determine whether cytokine genes are induced by sc 5-AED in hematopoietic tissues (bone marrow, spleen). We studied effects on serum cytokines and chemokines, and also analyzed the pharmacokinetics of 5-AED after sc administration and compared it with buccal delivery. 5-AED was administered 24 h before irradiation or sham-irradiation. Cytokine mRNAs were quantified by quantitative real-time PCR (QRT-PCR), and cytokine levels in serum by multiplex Luminex. 5-AED administration was associated with elevation of message for GM-CSF, IL-2, IL-3, IL-6, and IL-10 in spleen, and GM-CSF and IL-2 in bone marrow. Irradiation enhanced G-CSF, GM-CSF, IFN-gamma, TPO, IL-2, IL-3, IL-6, IL-10, and IL-12 in spleen, and GM-CSF, IFN-gamma, TPO, IL-3, and IL-10 in bone marrow. Serum levels of G-CSF were significantly elevated in 5-AED-treated mice 4 h after irradiation or sham-irradiation. Serum macrophage inflammatory protein-1gamma (MIP-1gamma) was significantly elevated 4 h after irradiation in 5-AED-treated mice. Plasma 5-AED peaked 2 h after sc injection (30 mg/kg), and remained significantly above control after 4 days, but not 8 days. The time course of plasma 5-AED after buccal delivery (60 mg/kg) was similar, but levels were significantly lower compared to sc delivery. Plasma 5-AED 24 h after administration was not significantly different between sc and buccal delivery. However, in contrast to many studies showing enhanced survival after sc administration of 5-AED, we found no effect on survival of buccal 5-AED. The results suggest that radioprotection is not dependent on the 5-AED concentration at the time of irradiation, but rather on events triggered during the first few hours after administration. The current results suggest that further studies are warranted to directly test the roles of cytokines in the radioprotective effects of 5-AED.

Quantitative effects of an intronic retroviral insertion on the transcription of the tyrosinase gene in recessive white chickens.

Recently, we reported the complete association of a retroviral insertion in intron 4 of the tyrosinase gene and the recessive white mutation (c) in chickens. The mutant allele carrying the retroviral insertion produced, in skin samples of 10-week-old chickens, aberrant tyrosinase transcripts that did not contain exon 5. In the present study, we performed serial molecular and statistical analyses on embryos and 10-week-old chickens to characterize the quantitative effect of the retroviral insertion on the expression pattern of tyrosinase in different tissues (skin and retina). By using quantitative real-time RT-PCR, we observed that the expression level of tyrosinase was significantly lower in recessive white chickens than in wild-type coloured chickens, but that this pattern was age- and tissue-dependent. The differential expression in skin was not significant in embryos, whereas it was highly significant in 10-week-old chickens. Furthermore, there was no difference in the expression of tyrosinase in the retinal pigment epithelium of animals with different genotypes; this corresponds to phenotypic data, which show pigmented eyes in both genotypes. These findings show that the retroviral insertion disturbs tyrosinase expression in the recessive white mutant chickens, and suggests that the regulation of tyrosinase expression in chickens differs between embryos and growing animals, as well as between skin and retina.

Extraintestinal focal infections in adults with nontyphoid Salmonella bacteraemia: predisposing factors and clinical outcome.

BACKGROUND: Nontyphoid Salmonella (NTS) isolates lead to not only self-limited, acute gastrointestinal infections, but also bacteraemia with or without extraintestinal focal infections (EFIs). The risk factors associated with EFIs in adults with NTS bacteraemia were not clearly elucidated. METHODS: In a medical center in southern Taiwan, patients aged > or = 18 years with NTS bacteraemia between January 1999 and June 2005 were included for analysis. RESULTS: Of 129 patients, 51 (39.5%) were complicated with EFIs. The most common EFI was mycotic aneurysm, followed by pleuropulmonary infections and spinal osteomyelitis. Compared to patients with primary bacteraemia, those with EFIs had higher leucocyte counts (P = 0.004) and higher serum levels of C-reactive protein (P < 0.0001). The development of EFIs was associated with a higher mortality, more severe septic manifestations, longer hospital stays and duration of antimicrobial therapy. Univariate analysis revealed that diabetes mellitus (P = 0.02), hypertension (P = 0.02) and chronic lung disease (P = 0.006) were significantly associated with EFIs. However, patients with malignancy (P = 0.01) and immunosuppressive therapy (P = 0.03) were less likely to develop EFIs. On the basis of multivariate analysis, an independent factor for the occurrence of EFIs was age [adjusted odds ratio (aOR) 1.05; 95% confidence interval (CI) 1.02-1.07; P < 0.0001], whilst malignancy was negatively associated with EFIs (aOR 0.16; 95% CI 0.14-0.78; P = 0.01). CONCLUSION: Amongst patients with NTS bacteraemia, EFIs often occurred in the aged, and were associated with a higher mortality and morbidity. Recognition of specific host factors is essential for identification of EFIs which often demand early surgical interventions and prolonged antimicrobial therapy.

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA.

RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adeno-associated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log(10) decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.