Comparison between [68Ga]Ga-PSMA-617 and [18F]FET PET as Imaging Biomarkers in Adult Recurrent Glioblastoma.

The aim of this prospective clinical study was to evaluate the potential of the prostate specific membrane antigen (PSMA) targeting ligand, [68Ga]-PSMA-Glu-NH-CO-NH-Lys-2-naphthyl-L-Ala-cyclohexane-DOTA ([68Ga]Ga-PSMA-617) as a positron emission tomography (PET) imaging biomarker in recurrent glioblastoma patients. Patients underwent [68Ga]Ga-PSMA-617 and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET scans on two separate days. [68Ga]Ga-PSMA-617 tumour selectivity was assessed by comparing tumour volume delineation and by assessing the intra-patient correlation between tumour uptake on [68Ga]Ga-PSMA-617 and [18F]FET PET images. [68Ga]Ga-PSMA-617 tumour specificity was evaluated by comparing its tumour-to-brain ratio (TBR) with [18F]FET TBR and its tumour volume with the magnetic resonance imaging (MRI) contrast-enhancing (CE) tumour volume. Ten patients were recruited in this study. [68Ga]Ga-PSMA-617-avid tumour volume was larger than the [18F]FET tumour volume (p = 0.063). There was a positive intra-patient correlation (median Pearson r = 0.51; p < 0.0001) between [68Ga]Ga-PSMA-617 and [18F]FET in the tumour volume. [68Ga]Ga-PSMA-617 had significantly higher TBR (p = 0.002) than [18F]FET. The [68Ga]Ga-PSMA-617-avid tumour volume was larger than the CE tumour volume (p = 0.0039). Overall, accumulation of [68Ga]-Ga-PSMA-617 beyond [18F]FET-avid tumour regions suggests the presence of neoangiogenesis in tumour regions that are not overly metabolically active yet. Higher tumour specificity suggests that [68Ga]-Ga-PSMA-617 could be a better imaging biomarker for recurrent tumour delineation and secondary treatment planning than [18F]FET and CE MRI.

Radical hysterectomy case volume and cervical cancer treatment in the era of COVID-19: A multi-site analysis of National Cancer Institute-designated Comprehensive Cancer Centers.

OBJECTIVE: To compare radical hysterectomy case volume, cancer stage, and biopsy-to-treatment time of invasive cervical cancer diagnosed before and after onset of the COVID-19 pandemic. METHODS: In a multi-institution retrospective cohort study conducted at 6 large, geographically diverse National Cancer Institute-designated cancer centers, patients treated for newly diagnosed invasive cervical cancer were classified into 2 temporal cohorts based on date of first gynecologic oncology encounter: (1) Pre-Pandemic: 3/1/2018-2/28/2020; (2) Pandemic & Recovery: 4/1/2020-12/31/2021. The primary outcome was total monthly radical hysterectomy case volume. Secondary outcomes were stage at diagnosis and diagnosis-to-treatment time. Statistical analyses used chi-squared and two sample t-tests. RESULTS: Between 3/1/2018-12/31/2021, 561 patients were diagnosed with cervical cancer. The Pre-Pandemic and Pandemic & Recovery cohorts had similar age, race, ethnicity, smoking status, and Body Mass Index (BMI). During Pandemic & Recovery, the mean monthly radical hysterectomy case volume decreased from 7[SD 2.8] to 5[SD 2.0] (p = 0.001), the proportion of patients diagnosed with Stage I disease dropped from 278/561 (49.5%) to 155/381 (40.7%), and diagnosis of stage II-IV disease increased from 281/561 (50.1%) to 224/381 (58.8%). Primary surgical management was less frequent (38.3% Pandemic & Recovery versus 46.7% Pre-Pandemic, p = 0.013) and fewer surgically-treated patients received surgery within 6 weeks of diagnosis (27.4% versus 38.9%; p = 0.025). CONCLUSIONS: Lower radical hysterectomy case volume, a shift to higher cervical cancer stage, and delay in surgical therapy were observed across the United States following the COVID-19 outbreak. Decreased surgical volume may result from lower detection of early-stage disease or other factors.

Feeding Black Pepper (Piper nigrum) or Exogenous Xylanase Improves the Blood Lipid Profile of Broiler Chickens Fed Wheat-Based Diets.

This study aimed to determine the impact of dietary black peppercorn (BP) and xylanase (XYL) alone or in combination on growth performance, dietary energy, nutrient digestibility and blood lipid profile when fed to male Ross 308 broiler chickens from the ages of 7 to 21 d. A wheat-soy-based basal feed that was formulated to be 0.42 MJ lower in metabolizable energy (ME) was mixed. The basal feed was then split into four batches, with the first batch set aside as the basal control; the second batch was supplemented with freshly milled BP; the third batch was supplemented with XYL; the fourth batch was supplemented with both BP and XYL, as in the previous two batches. Each diet was fed to eight pens, with two birds in a pen, following randomization. Feeding BP reduced bird growth and most of the digestibility coefficients but increased blood high-density lipoprotein (p < 0.05). Dietary XYL increased bird growth, dietary ME and nutrient digestibility (p < 0.05). In addition, XYL increased hepatic carotenoids and coenzyme Q10, but reduced blood low-density lipoprotein (p < 0.05). There were no BP by XYL interactions (p > 0.05) observed. Further research is needed to identify the optimum level of BP in broiler diets.

A universal reagent for detection of emerging diseases using bioengineered multifunctional yeast nanofragments.

Accurate and early detection of biomarkers provides the molecular evidence for disease management, allowing prompt actions and timely treatments to save lives. Multivalent biomolecular interactions between the probe and biomarker as well as controlled probe orientation on material surfaces are keys for highly sensitive detection. Here we report the bioengineering of programmable and multifunctional nanoprobes, which can provide rapid, specific and highly sensitive detection of emerging diseases in a range of widely used diagnostic systems. These nanoprobes composed of nanosized cell wall fragments, termed as synthetic bionanofragments (SynBioNFs), are generated by the fragmentation of genetically programmed yeast cells. SynBioNFs display multiple copies of biomolecules for high-affinity target binding and molecular handles for the precisely orientated attachment on surfaces used in diagnostic platforms. SynBioNFs are demonstrated for the capture and detection of SARS-CoV-2 virions using multiple diagnostic platforms, including surface-enhanced Raman scattering, fluorescence, electrochemical and colorimetric-based lateral flow systems with sensitivity comparable with the gold-standard reverse-transcription quantitative polymerase chain reaction.

Beyond post-operative readmissions: analysis of the impact of unplanned readmissions during primary treatment of advanced-stage epithelial ovarian cancer on long-term oncology outcome.

BACKGROUND: Multiple studies have assessed post-operative readmissions in advanced ovarian cancer. OBJECTIVE: To evaluate all unplanned readmissions during the primary treatment period of advanced epithelial ovarian cancer, and the impact of readmission on progression-free survival. METHODS: This was a single institution retrospective study from January 2008 to October 2018. Χ2/Fisher's exact and t-test, or Kruskal-Wallis test were used. Multivariable Cox proportional hazard models were used to assess the effect of covariates in progression-free survival analysis. RESULTS: A total of 484 patients (279 primary cytoreductive surgery, 205 neoadjuvant chemotherapy) were analyzed. In total, 272 of 484 (56%; 37% primary cytoreductive surgery, 32% neoadjuvant chemotherapy, p=0.29) patients were readmitted during the primary treatment period. Overall, 42.3% of the readmissions were surgery related, 47.8% were chemotherapy related, and 59.6% were cancer related but not related to surgery or chemotherapy, and each readmission could qualify for more than one reason. Readmitted patients had a higher rate of chronic kidney disease (4.1% vs 1.0%, p=0.038). Post-operative, chemotherapy, and cancer-related readmissions were similar between the two groups. However, the percentage of inpatient treatment days due to unplanned readmission was twice as high for primary cytoreductive surgery at 2.2% vs 1.3% for neoadjuvant chemotherapy (p<0.001). Despite longer readmissions in the primary cytoreductive surgery group, Cox regression analysis demonstrated that readmissions did not affect progression-free survival (HR=1.22, 95% CI 0.98 to 1.51; p=0.08). Primary cytoreductive surgery, higher modified Frailty Index, grade 3 disease, and optimal cytoreduction were associated with longer progression-free survival. CONCLUSIONS: In this study, 35% of the women with advanced ovarian cancer had at least one unplanned readmission during the entire treatment time. Patients treated by primary cytoreductive surgery spent more days during readmission than those with neoadjuvant chemotherapy. Readmissions did not affect progression-free survival and may not be valuable as a quality metric.

Early brain morphometrics from neonatal MRI predict motor and cognitive outcomes at 2-years corrected age in very preterm infants.

Infants born very preterm face a range of neurodevelopmental challenges in cognitive, language, behavioural and/or motor domains. Early accurate identification of those at risk of adverse neurodevelopmental outcomes, through clinical assessment and Magnetic Resonance Imaging (MRI), enables prognostication of outcomes and the initiation of targeted early interventions. This study utilises a prospective cohort of 181 infants born <31 weeks gestation, who had 3T MRIs acquired at 29-35 weeks postmenstrual age and a comprehensive neurodevelopmental evaluation at 2 years corrected age (CA). Cognitive, language and motor outcomes were assessed using the Bayley Scales of Infant and Toddler Development - Third Edition and functional motor outcomes using the Neuro-sensory Motor Developmental Assessment. By leveraging advanced structural MRI pre-processing steps to standardise the data, and the state-of-the-art developing Human Connectome Pipeline, early MRI biomarkers of neurodevelopmental outcomes were identified. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression, significant associations between brain structure on early MRIs with 2-year outcomes were obtained (r = 0.51 and 0.48 for motor and cognitive outcomes respectively) on an independent 25% of the data. Additionally, important brain biomarkers from early MRIs were identified, including cortical grey matter volumes, as well as cortical thickness and sulcal depth across the entire cortex. Adverse outcome on the Bayley-III motor and cognitive composite scores were accurately predicted, with an Area Under the Curve of 0.86 for both scores. These associations between 2-year outcomes and patient prognosis and early neonatal MRI measures demonstrate the utility of imaging prior to term equivalent age for providing earlier commencement of targeted interventions for infants born preterm.

Predicting motor and cognitive outcomes from MRIs of brain structure in children with acquired brain injury: A pilot study.

BACKGROUND: Acquired Brain Injury (ABI) describes a range of brain injuries occurring after birth, including tumor, traumatic brain injury or stroke. Although MRIs are routinely used for diagnosis, prediction of outcome following brain injury is challenging. Quantitative structural information from brain images may provide an opportunity to predict patient outcomes; however, due to the high prevalence of severe pathology in children with ABI, quantitative approaches must be robust to injury severity. METHODS: In this pilot cross-sectional study, automated quantitative measures were extracted from the MRIs of a cohort of children with ABI (n = 30, 8-16 years, follow up MRI taken 1.8-13.4 years after time of injury) as well as 36 typically developing controls with no brain injury (7-17 years) using a pathology-robust technique. Measures of brain volume, lesion volume and cortical morphology were associated with concurrent motor, behavioral, visual and communicative function using Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS: These regression models were validated on a separate test set (n = 8 of the ABI cohort), which revealed significant correlations between measures of brain structure with motor, cognitive, visual and communicative function (r = 0.65-0.85, all p < 0.01). Furthermore, comparisons of the structural measures to the typically developing cohort revealed overall reductions in global grey matter volume among the ABI cohort, as well as cortical thinning in several cortical areas. CONCLUSIONS: These preliminary associations reveal that motor and behavioral function can be estimated from MRI alone, highlighting the potential utility of the proposed pathology-robust MRI quantification tools to provide estimates of long-term clinical prognosis of children with ABI following injury.

Salivary Gland Bioengineering.

Salivary gland dysfunction affects millions globally, and tissue engineering may provide a promising therapeutic avenue. This review delves into the current state of salivary gland tissue engineering research, starting with a study of normal salivary gland development and function. It discusses the impact of fibrosis and cellular senescence on salivary gland pathologies. A diverse range of cells suitable for tissue engineering including cell lines, primary salivary gland cells, and stem cells are examined. Moreover, the paper explores various supportive biomaterials and scaffold fabrication methodologies that enhance salivary gland cell survival, differentiation, and engraftment. Innovative engineering strategies for the improvement of vascularization, innervation, and engraftment of engineered salivary gland tissue, including bioprinting, microfluidic hydrogels, mesh electronics, and nanoparticles, are also evaluated. This review underscores the promising potential of this research field for the treatment of salivary gland dysfunction and suggests directions for future exploration.

Multi-Omics, an Integrated Approach to Identify Novel Blood Biomarkers of Alzheimer's Disease.

The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD/MCI pathogenesis is unclear. This study compared the metabolomic and proteomic signature of plasma from cognitively normal (CN) and dementia patients diagnosed with MCI or AD, to identify specific cellular pathways and new biomarkers altered with the progression of the disease. We analysed 80 plasma samples from individuals with MCI or AD, as well as age- and gender-matched CN individuals, by utilising mass spectrometry methods and data analyses that included combined pathway analysis and model predictions. Several proteins clearly identified AD from the MCI and CN groups and included plasma actins, mannan-binding lectin serine protease 1, serum amyloid A2, fibronectin and extracellular matrix protein 1 and Keratin 9. The integrated pathway analysis showed various metabolic pathways were affected in AD, such as the arginine, alanine, aspartate, glutamate and pyruvate metabolism pathways. Therefore, our multi-omics approach identified novel plasma biomarkers for the MCI and AD groups, identified changes in metabolic processes, and may form the basis of a biomarker panel for stratifying dementia participants in future clinical trials.

CUB Domain-Containing Protein 1 (CDCP1) is a rational target for the development of imaging tracers and antibody-drug conjugates for cancer detection and therapy.

Rationale: An antibody-drug conjugate (ADC) is a targeted therapy consisting of a cytotoxic payload that is linked to an antibody which targets a protein enriched on malignant cells. Multiple ADCs are currently used clinically as anti-cancer agents significantly improving patient survival. Herein, we evaluated the rationale of targeting the cell surface oncoreceptor CUB domain-containing protein 1 (CDCP1) using ADCs and assessed the efficacy of CDCP1-directed ADCs against a range of malignant tumors. Methods: CDCP1 mRNA expression was evaluated using large transcriptomic datasets of normal/tumor samples for 23 types of cancer and 15 other normal organs, and CDCP1 protein expression was examined in 34 normal tissues, >300 samples from six types of cancer, and in 49 cancer cell lines. A recombinant human/mouse chimeric anti-CDCP1 antibody (ch10D7) was labelled with 89Zirconium or monomethyl auristatin E (MMAE) and tested in multiple pre-clinical cancer models including 36 cancer cell lines and three mouse xenograft models. Results: Analysis of CDCP1 expression indicates elevated CDCP1 expression in the majority of the cancers and restricted expression in normal human tissues. Antibody ch10D7 demonstrates a high affinity and specificity for CDCP1 inducing cell signalling via Src accompanied by rapid internalization of ch10D7/CDCP1 complexes in cancer cells. 89Zirconium-labelled ch10D7 accumulates in CDCP1 expressing cells enabling detection of pancreatic cancer xenografts in mice by PET imaging. Cytotoxicity of MMAE-labelled ch10D7 against kidney, colorectal, lung, ovarian, pancreatic and prostate cancer cells in vitro, correlates with the level of CDCP1 on the plasma membrane. ch10D7-MMAE displays robust anti-tumor effects against mouse xenograft models of pancreatic, colorectal and ovarian cancer. Conclusion: CDCP1 directed imaging agents will be useful for selecting cancer patients for personalized treatment with cytotoxin-loaded CDCP1 targeting agents including antibody-drug conjugates.

The relationship between chronic PTSD, cortical volumetry and white matter microstructure among Australian combat veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with volumetric and white matter microstructural changes among general and veteran populations. However, regions implicated have greatly varied and often conflict between studies, potentially due to confounding comorbidities within samples. This study compared grey matter volume and white matter microstructure among Australian combat veterans with and without a lifetime diagnosis of PTSD, in a homogenous sample assessed for known confounding comorbidities. METHODS: Sixty-eight male trauma-exposed veterans (16 PTSD-diagnosed; mean age 69 years) completed a battery of psychometric assessments and underwent magnetic resonance and diffusion tensor imaging. Analyses included tract-based spatial statistics, voxel-wise analyses, diffusion connectome-based group-wise analysis, and volumetric analysis. RESULTS: Significantly smaller grey matter volumes were observed in the left prefrontal cortex (P = 0.026), bilateral middle frontal gyrus (P = 0.021), and left anterior insula (P = 0.048) in the PTSD group compared to controls. Significant negative correlations were found between PTSD symptom severity and fractional anisotropy values in the left corticospinal tract (R2 = 0.34, P = 0.024) and left inferior cerebellar peduncle (R2 = 0.62, P = 0.016). No connectome-based differences in white matter properties were observed. CONCLUSIONS: Findings from this study reinforce reports of white matter alterations, as indicated by reduced fractional anisotropy values, in relation to PTSD symptom severity, as well as patterns of reduced volume in the prefrontal cortex. These results contribute to the developing profile of neuroanatomical differences uniquely attributable to veterans who suffer from chronic PTSD.

Adaptive and maladaptive humor styles are closely associated with burnout and professional fulfillment in members of the Society of Gynecologic Oncology.

Differences in individual humor styles (adaptive: affiliative, self-enhancing; maladaptive: aggressive, self-defeating) are associated with various wellness measures. This study examines the association of humor styles with professional fulfillment (PF) and burnout (BO) among Society of Gynecologic Oncology (SGO) members. SGO members were surveyed in 11/2020. The survey included 64 questions (32-item Humor Styles Questionnaire, 16-item Professional Fulfillment Index, and 16-item demographic and practice characteristics). Differences among faculty physicians (FAC), physician trainees (Res/Fel), and advanced practice providers (APP) were compared. Multivariable linear regression adjusted the association of humor styles with BO and PF for possible confounders. Of 1982 members invited to participate, 320 (16.1%) returned completed surveys (69.4% FAC, 23.4% Res/Fel, and 7.2% APP). All provider types scored highest for affiliative and lowest for aggressive humor. Res/Fel were more likely to employ aggressive and self-defeating humor styles than FAC and APP. One-third of respondents met criteria for BO and half experienced PF. FAC were more fulfilled than Res/Fel (p = 0.038). BO was negatively associated with self-enhancing and positively associated with self-defeating humor. Working > 60 h/week was associated with increased BO (p = 0.008) while trainee status (p = 0.010) and age > 55 (p = 0.008) were associated with decreased BO. PF was positively associated with self-enhancing and negatively associated with self-defeating humor. Spending > 10% of work hours on administrative duties led to lower PF (p = 0.008). Beyond advocating for less working hours and administrative duties, humor-based interventions to increase self-enhancing and reducing self-defeating humor use may lead to less BO and greater PF in SGO members, especially among trainees.

Stevia (Stevia rebaudiana) Improves Carotenoid Content in Eggs When Fed to Laying Hens.

Stevia rebaudiana Bertoni is a shrub with leaves that have a high concentration of carotenoids such as lutein and zeaxanthin. Egg yolks are a bioavailable source of lutein and zeaxanthin. The consumption of these carotenoids has been linked with improved human health. To investigate the impact of dried stevia leaves at 0%, 1% and 2% on the quality variables, the chemical composition and antioxidant content of eggs, the experiment involved 90 Hy-Line Brown laying hens, housed in 30 enriched layer cages, in groups of three from 22 to 26 weeks of age. The impact on the internal qualities of stored eggs was also examined. Yolks from hens fed stevia had an enriched color compared with the controls. At the end of the experiment, the whole egg, without shell, of birds fed 2% stevia had a higher total carotenoid content (p < 0.001) compared with birds fed 1% and 0% stevia, i.e., 5.16 (µg/g), 4.23 (µg/g) and 2.96 (µg/g), respectively. Storage reduced albumen height and increased albumen pH (p < 0.001). Stevia supplementation did not interact (p > 0.05) with storage time among the egg quality variables. Consuming eggs from hens fed stevia may increase carotenoids in human diet.

A Revised Markov Model Evaluating Oophorectomy at the Time of Hysterectomy for Benign Indication: Age 65 Years Revisited.

OBJECTIVE: To perform an updated Markov modeling to assess the optimal age for bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign indication. METHODS: We performed a literature review that assessed hazard ratios (HRs) for mortality by disease, age, hysterectomy with or without BSO, and estrogen therapy use. Base mortality rates were derived from national vital statistics data. A Markov model from reported HRs predicted the proportion of the population staying alive to age 80 years by 1-year and 5-year age groups at time of surgery, from age 45 to 55 years. Those younger than age 50 years were modeled as either taking postoperative estrogen or not; those 50 and older were modeled as not receiving estrogen. Computations were performed with R 3.5.1, using Bayesian integration for HR uncertainty. RESULTS: Performing salpingo-oophorectomy before age 50 years for those not taking estrogen yields a lower survival proportion to age 80 years than hysterectomy alone before age 50 years (52.8% [Bayesian CI 40.7-59.7] vs 63.5% [Bayesian CI 62.2-64.9]). At or after age 50 years, there were similar proportions of those living to age 80 years with hysterectomy alone (66.4%, Bayesian CI 65.0-67.6) compared with concurrent salpingo-oophorectomy (66.9%, Bayesian CI 64.4-69.0). Importantly, those taking estrogen when salpingo-oophorectomy was performed before age 50 years had similar proportions of cardiovascular disease, stroke, and people living to age 80 years as those undergoing hysterectomy alone or those undergoing hysterectomy and salpingo-oophorectomy at age 50 years and older. CONCLUSION: This updated Markov model argues for the consideration of concurrent salpingo-oophorectomy for patients who are undergoing hysterectomy at age 50 and older and suggests that initiating estrogen in those who need salpingo-oophorectomy before age 50 years mitigates increased mortality risk.

Positron emission tomography and magnetic resonance imaging of the brain in experimental human malaria, a prospective cohort study.

Cerebral malaria is the most serious manifestation of severe falciparum malaria. Sequestration of infected red blood cells and microvascular dysfunction are key contributing processes. Whether these processes occur in early stage disease prior to clinical manifestations is unknown. To help localize and understand these processes during the early stages of infection, we performed 18-F fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in volunteers with Plasmodium falciparum induced blood stage malaria (IBSM) infection, and compared results to individuals with P. vivax infection, in whom coma is rare. Seven healthy, malaria-naïve participants underwent imaging at baseline, and at early symptom onset a median 9 days following inoculation (n = 4 P. falciparum, n = 3 P. vivax). Participants with P. falciparum infection demonstrated marked lability in radiotracer uptake across all regions of the brain, exceeding expected normal variation (within subject coefficient of variation (wCV): 14.4%) compared to the relatively stable uptake in participants with P. vivax infection (wCV: 3.5%). No consistent imaging changes suggestive of microvascular dysfunction were observed in either group. Neuroimaging in early IBSM studies is safe and technically feasible, with preliminary results suggesting that differences in brain tropism between P. falciparum and P. vivax may occur very early in infection.

Reduced cortical cholinergic innervation measured using [18F]-FEOBV PET imaging correlates with cognitive decline in mild cognitive impairment.

Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. A validated method to directly quantify cortical cholinergic terminal integrity enables exploration of the involvement of this system in diverse cognitive profiles associated with dementia, particularly at a prodromal stage. In this study, we used the radiotracer [18F]-fluoroethoxybenzovesamicol (FEOBV) as a direct measure of cholinergic terminal integrity and investigated its value for the assessment of cholinergic denervation in the cortex and associated cognitive deficits. Eighteen participants (8 with mild cognitive impairment (MCI) and 10 cognitively unimpaired controls) underwent neuropsychological assessment and brain imaging using FEOBV and [18F]-florbetaben for amyloid-ß imaging. The MCI group showed a significant global reduction of FEOBV retention in the cortex and in the parietal and occipital cortices specifically compared to the control group. The global cortical FEOBV retention of all participants positively correlated with the BF, hippocampus and grey matter volumes, but no association was found between the global FEOBV retention and amyloid-ß status. Topographic profiles from voxel-wise analysis of FEOBV images revealed significant positive correlations with the cognitive domains associated with the underlying cortical areas. Overlapping profiles of decreased FEOBV were identified in correlation with impairment in executive function, attention and language, which covered the anterior cingulate gyrus, olfactory cortex, calcarine cortex, middle temporal gyrus and caudate nucleus. However, the absence of cortical atrophy in these areas suggested that reduced cholinergic terminal integrity in the cortex is an important factor underlying the observed cognitive decline in early dementia. Our results provide support for the utility and validity of FEOBV PET for quantitative assessment of region-specific cholinergic terminal integrity that could potentially be used for early detection of cholinergic dysfunction in dementia following further validation in larger cohorts.

Deposition of non-porous calcium phosphate shells onto liquid filled microcapsules.

The efficient encapsulation of small molecule active ingredients has been a challenge for many decades across many commercial applications. Recently, successful attempts to address this issue have included deposition of thin metal shells onto liquid filled polymer microcapsules or emulsion droplets to provide an impermeable barrier to diffusion. In this work we have developed a novel method to protect small molecule active ingredients by deposition of thin mineral shells. Platinum nanoparticles are used to catalyse and direct growth of a calcium phosphate shell onto liquid filled polymer microcapsules under various reaction conditions. Findings indicate that a non-porous protective shell is formed on the majority of the microcapsule population, with small concentrations of the core material being released only from those microcapsules with defects, over a 7 days period, when conducting forced release studies into a solvent for the core oil. The resulting microcapsules show no significant cell toxicity when exposed to HEK 293 cells for 72 h.