Mediterranean Diet Information on TikTok and Implications for Digital Health Promotion Research: Social Media Content Analysis.

BACKGROUND: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information. OBJECTIVE: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and opportunities for the use of TikTok in promoting the Mediterranean diet for healthy living. METHODS: The first-appearing 202 TikTok posts that resulted from a search of the hashtag #mediterraneandiet were downloaded and qualitatively examined. Post features and characteristics, poster information, and engagement metrics were extracted and synthesized across posts. Posts were categorized as those created by health professionals and those created by nonhealth professionals based on poster-reported credentials. In addition to descriptive statistics of the entire sample, we compared posts created by professionals and nonprofessionals for content using chi-square tests. RESULTS: TikTok posts varied in content, but posts that were developed by health professionals versus nonprofessionals were more likely to offer a definition of the Mediterranean diet (16/106, 15.1% vs 2/96, 2.1%; P=.001), use scientific citations to support claims (26/106, 24.5% vs 0/96, 0%; P<.001), and discuss specific nutrients (33/106, 31.1% vs 6/96, 6.3%; P<.001) and diseases related to the diet (27/106, 25.5% vs 5/96, 5.2%; P<.001) compared to posts created by nonhealth professionals. CONCLUSIONS: Social media holds promise as a venue to promote the Mediterranean diet, but the variability in information found in this study highlights the need to create clear definitions about the diet and its components when developing Mediterranean diet interventions that use new media structures.

Advances in CAR T Cell Therapy for Non-Small Cell Lung Cancer.

Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.

Imaging the Side Effects of CAR T Cell Therapy: A Primer for the Practicing Radiologist.

Chimeric antigen receptor (CAR) T cell therapy is a revolutionary form of immunotherapy that has proven to be efficacious in the treatment of many hematologic cancers. CARs are modified T lymphocytes that express an artificial receptor specific to a tumor-associated antigen. These engineered cells are then reintroduced to upregulate the host immune responses and eradicate malignant cells. While the use of CAR T cell therapy is rapidly expanding, little is known about how common side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) present radiographically. Here we provide a comprehensive review of how side effects present in different organ systems and how they can be optimally imaged. Early and accurate recognition of the radiographic presentation of these side effects is critical to the practicing radiologist and their patients so that these side effects can be promptly identified and treated.

Quantitative nanohistology of aging dermal collagen.

The skin is the largest organ in the body and is essential for protecting us from environmental stressors such as UV radiation, pollution, and pathogens. As we age, our skin undergoes complex changes that can affect its function, appearance, and health. These changes result from intrinsic (chronological) and extrinsic (environmental) factors that can cause damage to the skin's cells and extracellular matrix. As higher-resolution microscopical techniques, such as Atomic Force Microscopy (AFM), are being deployed to support histology, it is possible to explore the biophysical properties of the dermal scaffold's constituents, such as the collagen network. In this study, we demonstrate the use of our AFM-based quantitative nanohistology, performed directly on unfixed cryosections of 30 donors (female, Caucasian), to differentiate between dermal collagen from different age groups and anatomical sites. The initial 420 (10 × 10 µm2) Atomic Force Microscopy images were segmented into 42,000 (1 × 1 µm2) images before being classified according to four pre-defined empirical collagen structural biomarkers to quantify the structural heterogeneity of the dermal collagen. These markers include interfibrillar gap formation, undefined collagen structure, and registered or unregistered dense collagen fibrillar network with evident D-banding. The structural analysis was also complemented by extensive nanoindentation (∼1,000 curves) performed on individual fibrils from each section, yielding 30,000 indentation curves for this study. Principal Component Analysis was used to reduce the complexity of high-dimensional datasets. The % prevalence of the empirical collagen structural biomarkers between the papillary and reticular dermis for each section proves determinant in differentiating between the donors as a function of their age or the anatomical site (cheek or breast). A case of abnormal biological aging validated our markers and nanohistology approach. This case also highlighted the difference between chronological and biological aging regarding dermal collagen phenotyping. However, quantifying the impact of chronic and pathological conditions on the structure and function of collagen at the sub-micron level remains challenging and lengthy. By employing tools such as the Atomic Force Microscope as presented here, it is possible to start evaluating the complexity of the dermal matrix at the nanoscale and start identifying relevant collagen morphology which could be used toward histopathology standards.

Radiographic features of pneumonitis in patients treated with immunotherapy compared to traditional chemotherapy for non-small cell lung cancer.

BACKGROUND: Pneumonitis has been described as a side effect of immunotherapy as well as traditional chemotherapy. Although immune-related adverse event (IRAE) pneumonitis has been extensively characterized, the relationship between IRAE pneumonitis and pneumonitis secondary to chemotherapy is less clear. Here, we present the first analysis of radiographic features of pneumonitis secondary to immunotherapy compared to chemotherapy. METHODS: Using our radiology records system, we searched chest computed tomography (CT) reports for the term "pneumonitis". We evaluated medical records to establish chronicity of pneumonitis occurring after medication administration and excluded cases where radiation therapy appeared to be the cause of pneumonitis. We also obtained information regarding demographic, clinical, and treatment characteristics for comparison. RESULTS: Patients treated with immunotherapy demonstrated more specific features of pneumonitis including consolidation, ground glass opacities, septal thickening, traction bronchiectasis, and pulmonary nodules compared to those treated with chemotherapy. Immunotherapy treatment correlated with the development of pulmonary nodules (p = 0.048), and administration of more than one immunotherapy agent correlated with a greater incidence of development of nodules (p = 0.050). Radiographic features in patients treated with immunotherapy all decreased over time. Conversely, in patients treated with chemotherapy the incidence of ground glass opacities, traction bronchiectasis, pulmonary nodules, and mediastinal/hilar adenopathy increased over time. CONCLUSIONS: IRAE-pneumonitis has distinct features and a distinct clinical course compared to pneumonitis secondary to chemotherapy. Importantly, IRAE-pneumonitis features decreased over time, suggesting that careful consideration of the benefit-risk ratio may allow for continuation of immunotherapy in some patients who develop pneumonitis.

Impact of the COVID-19 Pandemic on Trends in Cardiothoracic Imaging.

Introduction: Here, we evaluate the effect of the COVID-19 pandemic on utilization of cardiothoracic imaging studies. Methods: We queried our radiology record system to retrospectively identify numbers of specific key cardiothoracic imaging studies for five years prior and during the COVID-19 pandemic. Statistical analysis was performed to evaluate changes in the number of exams in 2020 and 2021 compared to 2019. Results: Five-year retrospective analysis demonstrated progressive increases in nearly all cross-sectional studies. In 2020, daily chest radiograph utilization decreased with an overall number of daily radiographs of 406 (SD = 73.1) compared to 480 per day in 2019 (SD = 82.6) (p < 0.0001). Portable radiograph utilization was increased in 2020 averaging 320 (SD = 68.2) films daily in 2020 compared to 266 (SD = 29.1) in 2019 (p < 0.0001). Utilization of thoracic CT was decreased during the pandemic, with 21.8 (SD = 12.9) studies daily compared to 52.0 (SD = 21.4) (p < 0.0001) studies daily in 2019. Cardiac imaging utilization was also substantially decreased in 2020 compared to 2019, averaging a total of 3.8 (SD = 3.2) versus 10.8 (SD = 6.6) studies daily and 0.88 (SD = 1.7) versus 2.5 (SD = 2.3) studies daily for CT and MRI, respectively. Evaluation of cardiothoracic imaging for the subsequent 18 months after New York's entry to phase I recovery in June 2020 demonstrated that by one year after the emergence of COVID-19 imaging utilization had recovered to prepandemic levels. Cardiac imaging continued to increase throughout the chronic phase of the COVID-19 pandemic, reaching almost twice the prepandemic levels by the end of 2021. Conclusion: COVID-19 has had far-reaching effects on medicine and public health. Here, we demonstrate decreases in all cross-sectional cardiothoracic imaging studies, closely mirroring findings in other fields during the height of the pandemic, which have since rebounded.

The impact of the COVID-19 pandemic on neuroimaging volume in New York City.

BACKGROUND AND PURPOSE: The COVID-19 pandemic acutely disrupted all facets of healthcare, with future implications that are expected to resonate for many years. We investigated the effect of the pandemic on neuroimaging volume, hypothesizing that all representative studies would experience a reduction in volume, with those typically performed in the inpatient setting (noncontrast enhanced CT head and CTA head/neck) taking longer to recover to pre-pandemic volumes compared to studies typically performed in the outpatient setting (MR brain with and without and MR lumbar spine without). MATERIALS AND METHODS: We retrospectively queried our institution's radiology reporting system to collect weekly data for 1 year following the World Health Organization declaration of a pandemic (11 March 2020-9 March 2021) and compared them to imaging volumes from the previous year (11 March 2019-9 March 2020). We subsequently analyzed quarterly data (e.g., first quarter comparison: 3/11/2020-6/9/2020 was compared to 3/11/2019-6/9/2019). RESULTS: All studies experienced decreased volume during the first quarter of the year following onset of the COVID-19 pandemic, with noncontrast enhanced CT head failing to recover to pre-pandemic volumes. CTA head/neck actually surpassed pre-pandemic volume by the second quarter of the year. MRI brain w/wo and MRI lumbar spine without recovered to baseline volume by the second quarter. CONCLUSION: Noncontrast enhanced CT head did not recover pre-pandemic imaging volume. CTA head/neck volume initially decreased, however volume increased above pre-pandemic levels during the second quarter; this finding may be attributable to a prothrombotic state in COVID-19 patients.

Immunotherapy related pericardial effusion on chest CT.

BACKGROUND: Immunotherapy has become a critical class of anticancer therapy in recent years, functioning by releasing brakes on the immune system that ultimately results in immune cell activation which eliminates cancer cells. Immune related adverse events (IRAEs) are a specific type of adverse event described in patients taking checkpoint inhibitor immunotherapy which results from unrestrained immune activation. Immune related pericardial effusion has been described however has not been comprehensively characterized. Here, we present the most extensive report to date detailing this adverse event. METHODS: We queried our medical record system to retrospectively identify patients on checkpoint inhibitor therapy for lung cancer who subsequently developed pericardial effusion. We analyzed the clinical and radiographic characteristics, prior therapies, treatment for the effusion, and outcomes in patients with immune related pericardial effusion and compared them to similar patients with pericardial effusion not attributable to checkpoint inhibitor therapy. RESULTS: Our data demonstrate that most of these pericardial effusions were small and not clinically significant. The majority were successfully treated with steroids or resolved spontaneously. Anti-PD-1 inhibitors were the most common checkpoint inhibitor preceding pericardial effusion, and a significant number of patients who went on to develop IRAE pericardial effusion previously had treatment with carboplatin for their cancer. CONCLUSIONS: These data suggest that IRAE pericardial effusion is not a clinically significant adverse event however it sometimes leads to permanent discontinuation of checkpoint inhibitor therapy which is not necessary.

Deep Learning of Computed Tomography Virtual Wedge Resection for Prediction of Histologic Usual Interstitial Pneumonitis.

Rationale: The computed tomography (CT) pattern of definite or probable usual interstitial pneumonia (UIP) can be diagnostic of idiopathic pulmonary fibrosis and may obviate the need for invasive surgical biopsy. Few machine-learning studies have investigated the classification of interstitial lung disease (ILD) on CT imaging, but none have used histopathology as a reference standard.Objectives: To predict histopathologic UIP using deep learning of high-resolution computed tomography (HRCT).Methods: Institutional databases were retrospectively searched for consecutive patients with ILD, HRCT, and diagnostic histopathology from 2011 to 2014 (training cohort) and from 2016 to 2017 (testing cohort). A blinded expert radiologist and pulmonologist reviewed all training HRCT scans in consensus and classified HRCT scans based on the 2018 American Thoracic Society/European Respriatory Society/Japanese Respiratory Society/Latin American Thoracic Association diagnostic criteria for idiopathic pulmonary fibrosis. A convolutional neural network (CNN) was built accepting 4 × 4 × 2 cm virtual wedges of peripheral lung on HRCT as input and outputting the UIP histopathologic pattern. The CNN was trained and evaluated on the training cohort using fivefold cross validation and was then tested on the hold-out testing cohort. CNN and human performance were compared in the training cohort. Logistic regression and survival analyses were performed.Results: The CNN was trained on 221 patients (median age 60 yr; interquartile range [IQR], 53-66), including 71 patients (32%) with UIP or probable UIP histopathologic patterns. The CNN was tested on a separate hold-out cohort of 80 patients (median age 66 yr; IQR, 58-69), including 22 patients (27%) with UIP or probable UIP histopathologic patterns. An average of 516 wedges were generated per patient. The percentage of wedges with CNN-predicted UIP yielded a cross validation area under the curve of 74% for histopathological UIP pattern per patient. The optimal cutoff point for classifying patients on the training cohort was 16.5% of virtual lung wedges with CNN-predicted UIP and resulted in sensitivity and specificity of 74% and 58%, respectively, in the testing cohort. CNN-predicted UIP was associated with an increased risk of death or lung transplantation during cross validation (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P = 0.03).Conclusions: Virtual lung wedge resection in patients with ILD can be used as an input to a CNN for predicting the histopathologic UIP pattern and transplant-free survival.

Skin, Hair and Nail Supplements: An Evidence-Based Approach

Dermatology supplements, often marketed as "skin, hair, and nail" supplements, are becoming increasingly popular. However, many consumers lack an understanding of the science of dietary supplements or the specifics of the supplement industry. While certain supplements at the right dose in the right population may prove beneficial, the evidence is sparse for many supplements. In addition, the use of some supplements has resulted in serious adverse effects. From a regulatory standpoint, the US FDA recognizes dietary supplements as foods. This distinction has multiple ramifications, including the fact that manufacturers do not need to prove efficacy, safety, or quality prior to sale. Therefore, physicians and consumers must evaluate each supplement ingredient and formulation individually. This article outlines an evidence-based approach to assess dermatology supplements. As a starting point, all supplements should be evaluated for PPIES: purity, potency, interactions, efficacy, and safety.

A facile novel fluorocarbon copolymer solution coating process for improving platelet compatibility of titanium.

Titanium (Ti) and its alloys possess mechanical properties that are desirable in many biomedical applications compared to other metals. Furthermore, the native metal oxide layer that prevents further oxidation is also known to be biocompatible. However, clinical findings have shown that titanium and its alloys are prone to adverse bioreactions such as platelet adhesion and activation which could lead to thrombogenic complications. It has been found that surfaces modified with fluorocarbons could reduce the degree of both platelet adhesion and activation. Nevertheless, direct fluorocarbon deposition onto titanium substrates would require significant technical efforts. Instead, this research utilized a facile coating process with novel copolymers containing 2,2,2-trifluoroethyl methacrylate (TFEMA) and vinylphosphonic acid (VPA) to modify the titanium surface, giving the surface lower surface energy and higher hydrophobicity, significantly reducing the thrombus formation while exhibiting good cytocompatibility. The anchorage group, phosphonic acid provided by VPA, can be covalently bound to the oxide surface of titanium metal. Via free radical polymerization, VPA and TFEMA formed copolymers with different hydrophobicity were then used to modify titanium substrates, on which a series of surface characterization, in vitro platelet adhesion tests, and cytotoxicity assays were performed. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis of the copolymers and the modification of Ti substrates. The platelet adhesion tests showed significantly reduced amount of adherent platelets on certain copolymer-modified Ti substrates with low degrees of activation. The in vitro cytotoxicity assays further highlighted that the modifications conducted on Ti does not induce cytotoxicity.

Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis.

ALK receptor tyrosine kinase has been shown to be a therapeutic target in neuroblastoma. Germline ALK activating mutations are responsible for the majority of hereditary neuroblastoma and somatic ALK activating mutations are also frequently observed in sporadic cases of advanced NB. Crizotinib, a first-line therapy in the treatment of advanced non-small cell lung cancer (NSCLC) harboring ALK rearrangements, demonstrates striking efficacy against ALK-rearranged NB. However, crizotinib fails to effectively inhibit the activity of ALK when activating mutations are present within its kinase domain, as with the F1174L mutation. Here we show that a new ALK inhibitor AZD3463 effectively suppressed the proliferation of NB cell lines with wild type ALK (WT) as well as ALK activating mutations (F1174L and D1091N) by blocking the ALK-mediated PI3K/AKT/mTOR pathway and ultimately induced apoptosis and autophagy. In addition, AZD3463 enhanced the cytotoxic effects of doxorubicin on NB cells. AZD3463 also exhibited significant therapeutic efficacy on the growth of the NB tumors with WT and F1174L activating mutation ALK in orthotopic xenograft mouse models. These results indicate that AZD3463 is a promising therapeutic agent in the treatment of NB.

An anti-PSMA bivalent immunotoxin exhibits specificity and efficacy for prostate cancer imaging and therapy.

Prostate specific membrane antigen (PSMA) is overexpressed on prostate tumor cells and the neovascular endothelia various solid tumors. A bivalent immunotoxin generated by fusing a fold-back single-chain diabody derived from the Fv fragments of an anti-PSMA monoclonal antibody with a truncated diphtheria toxin (DT) containing the activity and translocation domains [A-dmDT390-scfbDb(PSMA)] might be suitable for targeted therapy of tumors that overexpress PSMA. In this study, a PSMA-positive and a PSMA-negative prostate cancer cell lines were treated with immunotoxin A-dmDT390-scfbDb(PSMA) in order to study the tumor targeting specificity and therapeutic potential of the immunotoxin. The cellular uptake and selective toxicity of the immunotoxin were evident in monolayer cultures of PSMA-positive LNCaP prostate cancer cells but not in cultures of PSMA-negative PC-3 prostate cancer cells. Cellular accumulation of A-dmDT390-scfbDb(PSMA) increased with increasing incubation times and concentrations in LNCaP cells. The proportion of apoptotic LNCaP cells increased upon incubation with increasing doses of the fold-back immunotoxin. Optical imaging and MRI with the Alexa Fluor 680-labeled A-dmDT390-scfbDb(PSMA) confirmed the specific targeting and therapeutic efficacy of this immunotoxin towards PSMA-positive LNCaP solid tumor xenografts in athymic nude mice.

Glucosamine-linked near-infrared fluorescent probes for imaging of solid tumor xenografts.

PURPOSE: Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one or more glucosamine (GlcN) moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer. PROCEDURES: Cellular uptake of the probes (1 µM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate-D: -(+)-glucosamine (cyp-GlcN), and D: -(+)-gluosamine-cypate-D: -(+)-gluosamine (cyp-2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging. RESULTS: The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp-GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp-2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively. CONCLUSION: Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp-GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging.

Changes in the nutrient content of american diets.

As obesity and being overweight continue to increase in the United States, public concern is growing about the quality of American diets. We compare the changes in nutrients contributed by major food groups in the periods 1953-1980 and 1981-2008 and find that there is reduced cholesterol intake and increased calcium intake, but the levels of food energy and total fats increase substantially. To understand how economic factors affect the overall nutritional quality of American diets, we estimate a complete food demand system and conduct a nutrient demand analysis. Among our findings, we conclude that some price manipulations such as subsidizing fruits and vegetables could be effective to increase produce consumption, but the effects of taxing fats to reduce the consumption of fats could be limited. Increasing income would improve intakes of nutrients such as calcium and various vitamins (likely now insufficient), but intakes of nutrients such as energy, saturated fats, and cholesterol (likely now excessive) would also rise with increased income.

Effects of prone and reverse trendelenburg positioning on ocular parameters.

BACKGROUND: : In a pilot study of awake volunteers, intraocular pressure (IOP), choroid layer thickness, and optic nerve diameter were shown to increase in the prone position over 5 h with a nonsignificant trend of attenuation using a 4-degree increase of table inclination. These effects have previously not been isolated from anesthetic and fluid administration over a prolonged period, using an adequate sample size. METHODS: : After institutional review board approval, 10 healthy volunteers underwent IOP measurement (Tono-Pen XL, Medtronic Solan, Jacksonville, FL) as well as choroidal thickness and optic nerve diameter assessment (Sonomed B-1000, Sonomed, Inc., Lake Success, NY, or the I System-ABD, Innovative Imaging, Inc., Sacramento, CA) on a Jackson table (Orthopedic Systems, Inc., Union City, CA), during 5 h horizontal prone and 5 h 4-degree reverse Trendelenburg positioning. Measurements were assessed as initial supine, initial prone, and hourly thereafter. Vital signs were recorded at each position and time point. RESULTS: : IOP, choroidal thickness, and optic nerve diameter were observed to increase with time in the prone position. A small degree of reverse Trendelenburg attenuated the increase in choroidal thickness but not IOP or optic nerve diameter. CONCLUSIONS: : Prolonged prone positioning increases IOP, choroid layer thickness, and optic nerve diameter independent of anesthetics and intravenous fluid infusion and 4 degrees of table inclination (15 cm of head to foot vertical disparity) may not attenuate these effects.

Measuring factors affecting grip strength in a Taiwan Chinese population and a comparison with consolidated norms.

We inquire whether assessment of an individual's upper limb function may be improved by using specific regional norms rather than consolidated global norms. Grip strengths were measured in a sample of 482 adults across Taiwan, and compared with consolidated norms. To ensure comparable conditions, our procedures were those recommended by the American Society of Hand Therapists (ASHT). Overall the mean grip strength of our sample was significantly (male 25%, female 27%) lower than consolidated norms derived from largely Caucasian populations. We investigated variables that might relate to this divergence. Results of ANOVA and stepwise multiple regression analysis showed that gender, age and palm length were effective predictors in grip strength. A regression equation was derived. When other variables were matched, palm length appeared an important discriminating factor. Further anthropometric and socio-economic factors also need investigation. Specific regional norms should provide more accuracy for ergonomists and health workers assessing an individual's upper limb function, and may avoid errors in appraisal. This paper suggests grip strength values for Taiwan.

Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA.

Cellular cytidine deaminases APOBEC3 family is a group of potent inhibitors for many exogenous and endogenous retroviruses. It has been demonstrated that they induce G to A hypermutations in the nascent retroviral DNA, resulting from the cytosine (C) to uracil (U) conversions in minus-stranded viral DNA. In this report, we have demonstrated that the result of C to U conversion in minus-stranded DNA of human immunodeficiency virus type 1 (HIV-1) could trigger a degradation of nascent viral DNA mediated by uracil DNA glycosylases-2 (UNG2) and apurinic/apyrimidinic endonuclease (APE). Since antiviral activity of APOBEC3G is partially affected by UNG2 inhibitor Ugi or UNG2-specific short-interfering RNA in virus-producing cells but not target cells, the virion-associated UNG2 most likely mediates this process. Interestingly, as APE-specific short-interfering RNA can also partially inhibit the anti-HIV-1 activity of APOBEC3G in virus-producing cells but not in target cells and APE molecules can be detected within HIV-1 virions, it seems that the required APE is also virion-associated. Furthermore, the in vitro cleavage experiment using uracil-containing single-stranded DNA as a template has demonstrated that the uracil-excising catalytic activity of virion-associated UNG2 can remove dU from the uracil-containing viral DNA and leave an abasic site, which could be further cleaved by virion-associated APE. Based upon our observations, we propose that the degradation of APOBEC3G-edited viral DNA mediated by virion-associated UNG2 and APE during or after reverse transcription could be partially responsible for the potent anti-HIV-1 effect by APOBEC3G in the absence of vif.

Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry.

Murine models that mimic the neuropathology of Alzheimer's disease (AD) have the potential to provide insight into the pathogenesis of the disease and lead to new strategies for the therapeutic management of afflicted patients. We used magnetic resonance imaging (MRI), design-based stereology, and high performance liquid chromatography (HPLC) to assess the age-related neuropathology in double transgenic mice that overexpress two AD-related proteins--amyloid precursor protein (APP) and presenilin 1 (PS1)--and age- and gender-matched wild-type (WT) controls. In mice ranging in age from 4-28 months, total volumes of the hippocampal formation (V (HF)) and whole brain (V (brain)) were quantified by the Cavalieri-point counting method on a systematic-random sample of coronal T2-weighted MRI images; the same stereological methods were used to quantify V (HF) and V (brain) after perfusion and histological processing. To assess changes in AD-type beta-amyloid (A beta) plaques, sections from the hippocampal formation and amylgdaloid complex of mice aged 5, 12, and 15 months were stained by Congo Red histochemistry. In aged mice with large numbers of amyloid plaques, systematic-random samples of sections were stained by GFAP immunocytochemistry to assess gender and genotype effects on total numbers of astrocytes. In addition, levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-HT metabolites were assayed by HPLC in fresh-frozen samples from neocortex, striatum, hippocampus, and brainstem. We confirmed age-related increases in amyloid plaques, beginning with a few plaques at 5 months of age and increasing densities by 12 and 15 months. At 15 months of age, there were robust genotype effects, but no gender effects, on GFAP-immunopositive astrocytes in the amygdaloid complex and hippocampus. There were no effects on monoamine levels in all brain regions examined, and no volume changes in hippocampal formation or whole brain as quantified on either neuroimages or tissue sections. Strong correlations were present between volume estimates from MRI images and histological sections, with about 85% reduction in mean V (HF) or mean V (brain) between MRI and processed histological sections. In summary, these findings show that the double transgenic expression of AD-type mutations is associated with age-related increases in amyloid plaques and astrocytosis; however, this model does not recapitulate the cortical atrophy or neurochemical changes that are characteristic of AD.