Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma.

Regarding the increased incidence and high mortality rate of malignant melanoma, practical early-detection methods are essential to improve patients' clinical outcomes. In this study, we successfully prepared novel picolinamide-benzamide (18F-FPABZA) and nicotinamide-benzamide (18F-FNABZA) conjugates and determined their biological characteristics. The radiochemical yields of 18F-FPABZA and 18F-FNABZA were 26 ± 5% and 1 ± 0.5%, respectively. 18F-FPABZA was more lipophilic (log P = 1.48) than 18F-FNABZA (log P = 0.68). The cellular uptake of 18F-FPABZA in melanotic B16F10 cells was relatively higher than that of 18F-FNABZA at 15 min post-incubation. However, both radiotracers did not retain in amelanotic A375 cells. The tumor-to-muscle ratios of 18F-FPABZA-injected B16F10 tumor-bearing mice increased from 7.6 ± 0.4 at 15 min post-injection (p.i.) to 27.5 ± 16.6 at 3 h p.i., while those administered with 18F-FNABZA did not show a similarly dramatic increase throughout the experimental period. The results obtained from biodistribution studies were consistent with those derived from microPET imaging. This study demonstrated that 18F-FPABZA is a promising melanin-targeting positron emission tomography (PET) probe for melanotic melanoma.

Evaluation of Radioiodinated Fluoronicotinamide/Fluoropicolinamide-Benzamide Derivatives as Theranostic Agents for Melanoma.

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of 131I-MIP-1145 to develop 131I-iodofluoropicolinamide benzamide (131I-IFPABZA) and 131I-iodofluoronicotiamide benzamide (131I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. 131I-IFPABZA (Log P = 2.01) was more lipophilic than 131I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with 131I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with 131I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of 131I-IFNABZA- and 131I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of 131I-IFNABZA with the melanin-targeted agents reported in the literature, 131I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using 131I-IFNABZA as a theranostic agent against melanoma.

Preparation and characterization of a novel Al(18)F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma.

Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. Previous studies have demonstrated the specific binding ability of benzamide moiety to melanin. In this study, we developed a novel (18)F-labeled NOTA-benzamide conjugate, Al(18)F-NOTA-BZA, which can be synthesized in 30min with a radiochemical yield of 20-35% and a radiochemical purity of >95%. Al(18)F-NOTA-BZA is highly hydrophilic (logP=-1.96) and shows good in vitro stability. Intravenous administration of Al(18)F-NOTA-BZA in two melanoma-bearing mouse models revealed highly specific uptake in B16F0 melanotic melanoma (6.67±0.91 and 1.50±0.26%ID/g at 15 and 120min p.i., respectively), but not in A375 amelanotic melanoma (0.87±0.21 and 0.24±0.09%ID/g at 15 and 120min p.i., respectively). The clearance from most normal tissues was fast. A microPET scan of Al(18)F-NOTA-BZA-injected mice also displayed high-contrast tumor images as compared with normal organs. Owing to the favorable in vivo distribution of Al(18)F-NOTA-BZA after intravenous administration, the estimated absorption dose was low in all normal organs and tissues. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and thelow projected human dosimetry supported that Al(18)F-NOTA-BZA is a very promising melanin-specific PET probe for melanin-positive melanoma.

Voice-Related Quality of Life Outcomes from Pneumatic Artificial Laryngeal and Esophageal Speakers.

The self-reporting voice-related quality of life (V-RQOL) instrument has been viewed as a modular index of quality of life for speakers using tracheoesophageal, esophageal (ES), or electrolaryngeal speech. However, V-RQOL has never been studied with pneumatic artificial laryngeal (PA) individuals. This study attempted to quantify the self-assessed voice-related performance of PA and ES speakers in Taiwan via the V-RQOL questionnaire, and further to compare the results for PA and ES speakers. METHODS: V-RQOL was assessed in 79 PA and 25 ES speakers undergoing total laryngectomy without using tracheoesophageal puncture. Data were collected from members of Taiwan's Association of Laryngectomees. RESULTS: There was no significant difference between PA and ES participants in social-emotional, physical functioning and total scores, suggesting both may consider their quality of life comparable with each other. In ES participants, there was a significant effect of time after total laryngectomy in physical functioning and total scores. CONCLUSIONS: PA speakers did not exhibit more dissatisfaction or disability than ES speakers on 10 statements in the V-RQOL, but after total laryngectomy the ES have been shown to improve over time. Information on the experience of PA and ES speakers could be used by clinicians to inform patients of potential outcomes, and help them select suitable rehabilitation techniques.

Identifying Preferred Appearance and Functional Requirements of Aged Care Robots Among Older Chinese Immigrants: Cross-Sectional Study.

Background: Older Chinese immigrants constitute the largest older Asian ethnic population in New Zealand. Aging in a foreign land can be complex, presenting increasing challenges for gerontology scholars, practitioners, and policy makers. Older Chinese immigrants are more susceptible to experiencing loneliness and social isolation compared to native older people, primarily due to language, transportation, and cultural barriers. These factors subsequently impact their physical and mental health. With advancements in robotic technology, aged care robots are being applied to support older people with their daily living needs. However, studies on using robots with older immigrants living in the community are sparse. Their preferences for the appearance and function of aged care robots are unclear, which impacts the acceptance and usability of robots, highlighting the need for a user-centered design approach. Objective: This study aims to explore older Chinese immigrants' needs and preferences toward the appearance and function of aged care robots and to examine their relationships with the demographic characteristics of participants. Methods: A cross-sectional design was used in this study, which was undertaken between March and May 2020. A total of 103 participants completed a web-based survey. Results: The average age of participants was 68.7 (SD 5.5) years. The results suggest that 41.7% (n=43) of the 103 participants preferred a humanlike adult appearance, while 32% (n=33) suggested an animallike appearance. These participants reported higher scores in both rigorousness and friendliness compared to others who preferred different robot appearances. Participants expressed a greater preference for the functions of housework assistance (n=86, 83.5%), language translation (n=79, 76.7%), health monitoring (n=78, 75.7%), facial expressions (n=77, 74.8%), news reading (n=66, 64.1%), and security monitoring (n=65, 63.1%). These preferences were found to be significantly associated with marital status, financial status, and duration of immigration. Conclusions: To support immigrant populations to age well in a foreign country and address the growing shortage of health and social professionals, it is important to develop reliable robotic technology services that are tailored based on the needs and preferences of individuals. We collected and compared the perspectives of immigrant and nonimmigrant participants on using robots to support aging in place. The results on users' needs and preferences inform robotic technology services, indicating a need to prioritize older Chinese immigrants' preference toward aged care robots that perform housework assistance, language translation, and health and safety monitoring, and robots with humanlike features.

Impacts of using different standard populations in calculating age-standardised death rates when age-specific death rates in the populations being compared do not have a consistent relationship: a cross-sectional population-based observational study on US state HIV death rates.

OBJECTIVE: To examine if the rankings of state HIV age-standardised death rates (SDRs) would be different if different standard populations (SPs) were used when age-specific death rates (ASDRs) in states being compared do not have a consistent relationship. DESIGN: A cross-sectional population-based observational study. SETTING: 36 states in the USA. PARTICIPANTS: Residents living in the 36 states. MAIN OUTCOME MEASURES: HIV SDR by state using two SPs, namely US2000 and US2020. RESULTS: US HIV ASDR by state did not have consistent relationships. Of 36 states analysed, the HIV death rates of people aged 55-64 years were higher than people aged 45-54 years in 20 states; on the contrary, the HIV death rates of people aged 55-64 years were lower than people aged 45-54 years in 16 states. No change in ranking in 19 states and change in ranking in 17 states. Of the 17 states whose rankings changed, the rankings of 9 states calculated using US2000 were higher (lower SDR) than those calculated using US2020; in 8 states, the rankings were lower (higher SDR). The states with the greatest changes in rankings between US2000 and US2020 were Kentucky (12th and 9th, respectively) and Massachusetts (8th and 11th, respectively). CONCLUSIONS: Calculating SDR using elder SP (US2020) would disproportionately increase the SDR in states with peak HIV death rate in older adults than those used younger SP (US2000).

Association between loneliness and acceptance of using robots and pets as companions among older Chinese immigrants during the COVID-19 pandemic.

OBJECTIVES: To examine loneliness experienced by middle-aged and older Chinese immigrants and its association with accepting technology as a companion (apps, Internet and robots) versus owning pets, when social distancing measures were implemented in New Zealand during the first COVID-19 outbreak. METHODS: This study conducted a community-based cross-sectional survey. Chinese immigrants who were 45-87 years old (n = 173) were invited to answer an online survey in the Chinese language, collecting demographic data, responses to the 6-item De Jong Gierveld Loneliness Scale and experiences in using technology and pet ownership. Descriptive analyses and inferential statistics tests were utilised in the data analysis. RESULTS: A moderate level of overall loneliness with a mean score of 3.68 (SD 1.84), ranging from 0 to 6, was reported by participants. Emotional and social loneliness ranged from 0 to 3 with mean scores of 1.69 (SD 0.98) and 1.99 (SD 1.24), respectively. Self-reported health, financial status, English language abilities, transportation and experiences of using the Internet and apps were significantly related to experiencing loneliness. Loneliness had a weak association with acceptance of robots and pets, but 67.8% and 58.3% of participants who felt lonely, accepted companionship of robots and pets, respectively. CONCLUSIONS: The level of loneliness among older and middle-aged immigrants increased during the COVID-19 pandemic. Further evidence of the specific dimensions of loneliness and the utility of technology to alleviate loneliness among immigrant groups is needed. Interventions tailored for older people with specific cultural requirements to address loneliness are needed.

Radiometal-Labeled Chitosan Microspheres as Transarterial Radioembolization Agents against Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (111In/177Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 µm for TARE. The radiochemical yields of 111In/177Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the 111In/177Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administration. Except for liver accumulation, radioactivity in each normal organ was less than 1% of the injected radioactivity (%IA) at 72 h after injection. At 10 days after injection of 177Lu-DTPA-CMS (18.6 ± 1.3 MBq), the size of the hepatoma was significantly reduced by around 81%, while that of the rats in the control group continued to grow. This study demonstrated the effectiveness of 177Lu-DTPA-CMS in the treatment of N1-S1 hepatoma. 111In/177Lu-DTPA-CMS have the potential to be a superior theranostic pair for the treatment of clinical hepatoma.

The Mandarin Voice Handicap Index for Laryngectomees With Pneumatic Artificial Laryngeal and Esophageal Speech.

Purpose The Voice Handicap Index (VHI) questionnaire assesses the impact of total laryngectomy on voice-related quality of life. This study evaluates the Mandarin VHI, including its internal consistency, test-retest reliability, content validity, and differences in scores for Mandarin alaryngeal patients with pneumatic artificial laryngeal (PA) and esophageal (ES) speech. Method Translation and validation of the VHI questionnaire was performed through the forward-backward translation technique. This study used a sample of 78 PA and 23 ES participants from Taiwan who completed the Mandarin VHI. Forty-two of the alaryngeal participants completed the Mandarin VHI twice over a period of 7-63 days. Results The measurement of the internal consistency of the Mandarin VHI showed a high Cronbach's alpha coefficient for the total score (.975) and the functional (.930), physical (.939), and emotional (.938) subscales. Based on the results of the intraclass correlation coefficients, good test-retest reliability for the total and domain scores was found (intraclass correlation coefficient = .827-.863). Conclusion The Mandarin VHI was validated as an instrument with proper internal consistency and reliability, which supports the Mandarin VHI as a valid instrument for the self-evaluation of handicaps related to voice problems in PA and ES speakers.

Health Promotion and Disease Prevention Interventions for the Elderly: A Scoping Review from 2015-2019.

In this study, a scoping review method is used to review the distribution and trends in health promotion research and explore the use and contribution of eHealth technologies in health promotion in the elderly. The study includes six search databases: PubMed, CINAHL, the CochraneLibrary, EMBASE, PubPsych, and ERIC (EBSCOhost), and studies published from January 2015 to October 2019, written in English, were included and analyzed. The findings of the study reveal that the amount of literature on promoting health for the elderly has increased, and some specific types of interventions are still favored in current health promotion efforts for older adults. The most commonly used methods were found to be health promotion (n = 322), followed by screening (n = 264), primary prevention (n = 114), and finally social support (n = 72). Beyond the above interventions, eHealth technology is also used in health promotion activities to prevent the elderly from falling and to improve home safety, etc. However, although the application of eHealth technology has been applied in areas such as fall prevention, mental health promotion, and home security monitoring, it is still immature, and thus more rigorous research is needed in different areas, especially in older populations, various professions, women, and people with dementia.

VLDL and LDL, but not HDL, promote breast cancer cell proliferation, metastasis and angiogenesis.

Abnormal lipoprotein profiles are associated with breast cancer progression. However, the mechanisms linking abnormal lipoprotein levels to breast cancer progression, especially metastasis, remain unclear. Herein, we found that L1 and L5 subfractions of LDL and VLDL, but not HDL, enhanced breast cancer cell viability. L1, L5, and VLDL also increased the in vitro tumorigenesis of breast cancer cells in anchorage-independent soft agar assay. In addition, L1, L5, and VLDL, but not HDL, increased the levels of mesenchymal markers Slug, Vimentin, and ß-Catenin, and promoted breast cancer cell migration and invasion. L1, L5, and VLDL increased Akt Ser473 phosphorylation and promoted cell migration, which were reversed by the PI3K/Akt inhibitor wortmannin. Further in vitro angiogenesis assay and cytokine array analysis demonstrated that L1, L5, and VLDL enhanced secretion of angiogenic factors in breast cancer cells and promoted angiogenic activity. However, only VLDL reduced anchorage-dependent cell death and promoted lung metastasis in nude mice. In summary, our data suggest that L1, L5, and especially VLDL promote breast cancer progression and metastasis through Akt-induced EMT and angiogenesis, and provide a novel mechanism of how dyslipoproteinemia promotes breast cancer progression.

Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation.

PURPOSE: Visfatin is an adipocytokine involved in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings. EXPERIMENTAL DESIGN: Associations of serum visfatin with clinicopathologic characteristics and patient survival were assessed with Cox regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were used to inhibit c-Abl and STAT3 activation, respectively. RESULTS: Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatin-promoted in vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was observed in zebrafish xenografted with visfatin-pretreated breast cancer cells. Tumor growth and lung metastasis occurred in visfatin-administered mice xenografted with breast cancer cells. Tail vein-injected mice with visfatin-pretreated breast cancer cells showed increased lung metastasis, which was suppressed by imatinib. CONCLUSIONS: Serum visfatin levels in breast cancer patients reveal potential prognostic values, and our findings that visfatin promoted breast cancer through activation of c-Abl and STAT3 may provide an important molecular basis for future design of targeted therapies that take into account different serum visfatin levels in breast cancer. Clin Cancer Res; 22(17); 4478-90. ©2016 AACR.