The Relationships between Caregiver Burden, Physical Frailty, Race, Behavioral and Psychological Symptoms (BPSD), and Other Associated Variables: An Exploratory Study.

Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which is an important social determinant of health outcomes in the United States. To examine these interactions, we conducted a cross-sectional exploratory study based on a model by Sugimoto and colleagues. Materials and Methods: The sample comprised 85 patient-caregiver dyads (58% White) seen in four centers in diverse regions of New York State. All patients met DSM5 criteria for a major neurocognitive disorder, had a Clinical Dementia Rating sum score of ≥3, and Mini-Mental State Examination (MMSE) score of 10 to 26. Other measures included the SHARE-Frailty Instrument(FI), the Neuropsychiatric Inventory (NPI) to assess BPSD, Zarit's Caregiver Burden Interview (CBI), Lawton's Activities of Daily Living (ADL) Scale, the MMSE, the Cumulative Illness Rating Scale for Geriatrics (CIRSG), age, and gender. Results: In our sample, 59% met the criteria for prefrail/subsyndromal or frail/syndromal (SSF) on the SHARE-FI. SSF had significant direct effects on the NPI and significant indirect effects on the CBI mediated through the NPI; the NPI had significant direct effects on the CBI. Race (White) had significant direct effects on the CBI (higher) and SSF (lower) but did not have significant indirect effects on the CBI. MMSE, ADL, and CIRSG were not significantly associated with the NPI or the CBI. Conclusions: Our analysis demonstrated that frailty, race, BPSD, and caregiver burden may directly or indirectly influence one another, and therefore should be considered essential elements of dementia assessment, care, and research. These results must be viewed as provisional and should be replicated longitudinally with larger samples.

The utility of self-rated health in older adults with schizophrenia.

OBJECTIVES: Self-rated health is one of the most widely used measures in gerontology, but it has not been evaluated systematically in older adults with schizophrenia (OAS). Therefore, the aim of this study was to determine the utility of self-rated health in OAS by examining its influencing factors and contrasting these findings with a community comparison (CC) group. METHOD: We compared 249 community-dwelling persons aged 55 years and older having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnosis of schizophrenia arising before age 45 years with a demographically similar group of 113 older adults in the general community. Using a modified version of Ocampo's model of self-rated health, we identified 12 predictor variables within 5 dimensions. RESULTS: There were no significant differences in self-health ratings between the OAS and the CC groups. Six of the 12 variables in the model significantly correlated with self-rated health in both groups. In linear regression analysis, three variables were significantly associated with self-rated health in both groups: Center for Epidemiological Studies-Depression score, number of physical disorders, and perception of self-health versus others. Self-rated health assessment was not associated with positive or negative symptoms or lack of awareness of mental illness. CONCLUSION: There was a striking similarity in the factors influencing self-rated health in the two groups. The findings were consistent with results of previous gerontological studies that self-rated health reflects elements of psychiatric and physical well-being, as well as perceptions of their age peers. Our results support the use of self-rated health as a legitimate clinical and research measure in OAS.

Recovery and Recovering in Older Adults with Schizophrenia: A 5-Tier Model.

RATIONALE: There are little recent data on clinical recovery in older adults with schizophrenia. This exploratory study uses an empirically measurable construct to address this issue. METHODS: From an original sample of 248 community-dwelling persons aged 55 and over with early-onset schizophrenia spectrum disorder, a subsample of 102 persons was reassessed at a mean of 52 months. Clinical recovery required meeting criteria for its two components: clinical remission and community integration. RESULTS: Prospective analysis generated a 5-tier taxonomy of recovery in which 12% remained persistently in clinical recovery at both baseline and follow-up (Tier 1) and 18% never met criteria of clinical recovery (Tier 5). The remaining 70% exhibited a variety of components of clinical recovery at baseline and follow-up (Tiers 2, 3, and 4). CONCLUSION: The findings generated a dynamic picture of recovery, with most persons being in varying states of "recovering." The 5-tier taxonomy of recovery adumbrated potential treatment strategies for each tier.

Computerized cognitive performance assessments in the Brooklyn Cognitive Impairments in Health Disparities Pilot Study.

INTRODUCTION: Detecting cognitive impairment in diverse, health disparities communities is an urgent health care priority. METHODS: The Brooklyn Cognitive Impairments in Health Disparities Pilot Study investigated quantitative aspects and liking of a computerized cognitive performance assessment, Cognigram, among individuals ≥ 40 years in traditional and nontraditional primary care settings. RESULTS: Cognigram was piloted in the Emergency Department, Family Medicine, and Geriatric Psychiatry clinics: 58 adults (23 men, 35 women), 67.9 ± 9.8 years (range 43-91), completed the Cognigram and 5-item liking survey. The observed liking range was 2 to maximum score 5 (67% scored 4-5; no sex or age differences). DISCUSSION: The Cognigram was well liked in waiting rooms of primary care settings. Assistance from a trained adult and clinic endorsement were keys to success. How the Cognigram performs in a geographically compact, population-dense global setting, such as Brooklyn with high vascular disease risk and a plethora of health disparities, is being tested.

Lessons in Membrane Engineering for Octanoic Acid Production from Environmental Escherichia coli Isolates.

Fermentative production of many attractive biorenewable fuels and chemicals is limited by product toxicity in the form of damage to the microbial cell membrane. Metabolic engineering of the production organism can help mitigate this problem, but there is a need for identification and prioritization of the most effective engineering targets. Here, we use a set of previously characterized environmental Escherichia coli isolates with high tolerance and production of octanoic acid, a model membrane-damaging biorenewable product, as a case study for identifying and prioritizing membrane engineering strategies. This characterization identified differences in the membrane lipid composition, fluidity, integrity, and cell surface hydrophobicity from those of the lab strain MG1655. Consistent with previous publications, decreased membrane fluidity was associated with increased fatty acid production ability. Maintenance of high membrane integrity or longer membrane lipids seemed to be of less importance than fluidity. Cell surface hydrophobicity was also directly associated with fatty acid production titers, with the strength of this association demonstrated by plasmid-based expression of the multiple stress resistance outer membrane protein BhsA. This expression of bhsA was effective in altering hydrophobicity, but the direction and magnitude of the change differed between strains. Thus, additional strategies are needed to reliably engineer cell surface hydrophobicity. This work demonstrates the ability of environmental microbiological studies to impact the metabolic engineering design-build-test-learn cycle and possibly increase the economic viability of fermentative bioprocesses.IMPORTANCE The production of bulk fuels and chemicals in a bio-based fermentation process requires high product titers. This is often difficult to achieve, because many of the target molecules damage the membrane of the microbial cell factory. Engineering the composition of the membrane in order to decrease its vulnerability to this damage has proven to be an effective strategy for improving bioproduction, but additional strategies and engineering targets are needed. Here, we studied a small set of environmental Escherichia coli isolates that have higher production titers of octanoic acid, a model biorenewable chemical, than those of the lab strain MG1655. We found that membrane fluidity and cell surface hydrophobicity are strongly associated with improved octanoic acid production. Fewer genetic modification strategies have been demonstrated for tuning hydrophobicity relative to fluidity, leading to the conclusion that there is a need for expanding hydrophobicity engineering strategies in E. coli.

Late-life psychosis: diagnosis and treatment.

Psychosis is one of the most common conditions in later life with a lifetime risk of 23 %. Despite its high prevalence, late-onset psychosis remains a diagnostic and treatment dilemma. There are no reliable pathognomonic signs to distinguish primary or secondary psychosis. Primary psychosis is a diagnosis of exclusion and the clinician must rule out secondary causes. Approximately 60 % of older patients with newly incident psychosis have a secondary psychosis. In this article, we review current, evidence-based diagnostic and treatment approaches for this heterogeneous condition, emphasizing a thorough evaluation for the "six d's" of late-life psychosis (delirium, disease, drugs dementia, depression, delusions). Treatment is geared towards the specific cause of psychosis and tailored based on comorbid conditions. Frequently, environmental and psychosocial interventions are first-line treatments with the judicious use of pharmacotherapy as needed. There is an enormous gap between the prevalence of psychotic disorders in older adults and the availability of evidence-based treatment. The dramatic growth in the elderly population over the first half of this century creates a compelling need to address this gap.

Mental disorder, service use, and barriers to care among 500 homeless people in 3 different urban settings.

OBJECTIVE: To determine the standardized rates of mental disorder, health service use and barriers to care in a representatively diverse sample of homeless adults in three different sized urban centers in British Columbia, Canada. METHOD: Five hundred homeless adults from Vancouver, Victoria and Prince George were recruited. The MINI-International Neuropsychiatric Interview PLUS was used to determine current and lifetime rates of mental disorder, mental disorder episodes and suicidality. Health service use and barriers to care were recorded. RESULTS: Overall, 92.8 % of participants met criteria for a current mental disorder: 82.6 % for alcohol or drug dependence, 57.3 % anxiety disorder, 31.5 % mood disorder. Over half (53.4 %) met criteria for a concurrent disorder. Only 14.9 % had seen a psychiatrist and 12.7 % a mental health team in the year prior to the survey. Most common barriers included being poorly connected to the system of care and issues related to homelessness. Mental disorder rates across sites were high, however, differences were found that reflected the composition of the samples. CONCLUSION: Improving the mental health state of the homeless will require significant capacity for mental health and concurrent disorder programming that is tailored to the community it intends to serve. Demographic features of the population may help in directing assessments of need.

Frailty: A Multidimensional Biopsychosocial Syndrome.

The original conceptual landscape of frailty has evolved into a complex, multidimensional biopsychosocial syndrome. This has broadened the field to now include social and behavioral scientists and clinicians from a wide range of specialties. This article aims to provide an updated overview of this conceptual change by examining the emerging definitions of physical, cognitive, social, and psychological frailty; the tools used for diagnosis and assessment of these domains; the epidemiology of the domains; their pathogenesis, risk factors, and course; frameworks for prevention and treatment; and unresolved issues affecting the field.

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities.

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy.

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

High-resolution ultrasound imaging: a novel technique for the noninvasive in vivo analysis of endometriotic lesion and cyst formation in small animal models.

Endometriosis, the presence of endometrial tissue at ectopic sites, is a highly prevalent gynecological disease severely affecting a patient's quality of life. To analyze the mechanisms involved in the disease and to identify new molecular targets for effective therapies, small animal models are an important approach. Herein, we report the first use of high-resolution ultrasound imaging for the in vivo analysis of intraperitoneal endometriotic lesions in mice. This noninvasive technology allows for the repetitive quantitative analysis of growth, cyst development, and adhesion formation of endometriotic lesions with a low intra- and interobserver variability. Moreover, it enables one to easily differentiate between endometrial cysts and stroma. Accordingly, volume measurements of both endometrial cysts and stroma indicated that the initial establishment of endometriotic lesions is associated with enhanced cellular proliferation, followed by a phase of increased secretory activity of endometrial glands. Results of ultrasound analysis correlated well with measurements of lesion volumes by caliper and histology. Importantly, ultrasound imaging could be performed repetitively and noninvasively and reflected best the in vivo situation. The technique could further be demonstrated to successfully monitor the significant inhibition of growth of endometriotic lesions after specific estrogen receptor destabilizator treatment. Thus, high-resolution ultrasound imaging represents an important tool for future preclinical small animal studies, which address the pathophysiology of endometriosis and the development of new treatment strategies.

Advances in the Conceptualization and Study of Schizophrenia in Later Life: 2020 Update.

A crisis looms as research and clinical programs have not kept pace with dramatic increases in the number of older adults with schizophrenia. This article provides an overview of the advances in the conceptualization and study of schizophrenia in later life. Theoretic and clinical models in psychiatry and gerontology are integrated. Specifically, recovery is examined in the context of aging, how clinical dimensionality affects diagnoses in older adults, how various features of schizophrenia are implicated in models of accelerated and paradoxic aging, and how outcome in later life is a more dynamic and heterogeneous than assumed previously.

The ImmunoCAP Rapid Wheeze/Rhinitis Child test is useful in the initial allergy diagnosis of children with respiratory symptoms.

Recurrent upper or lower respiratory symptoms, possibly allergy-related, are very frequent in childhood. It is therefore important that physicians involved in the primary care of these children have an accurate initial diagnostic tool available. In this study, we investigated the value of an in vitro diagnostic device testing 10 common allergens, the ImmunoCAP Rapid Wheeze/Rhinitis Child, for the primary evaluation of allergy. Children with non-infectious upper or lower respiratory symptoms possibly related to allergy were recruited in the primary health care setting of private practices of physician trained in immunology/allergology. The investigators carried out their usual diagnostic work-up including IgE tests, and the ImmunoCAP Rapid test was performed with capillary whole blood in a blinded way to the investigator. The investigators' conclusions on major triggering allergens were compared to the ImmunoCAP Rapid test results. In the whole patient population (n = 185), the sensitivity of the ImmunoCAP Rapid test for unveiling allergic disease was 92% (95% CI: 86-96%) and the specificity 97% (95% CI: 86-100%). Current guidelines for allergy diagnosis suggest screening children with recurrent, moderate/severe diseases for allergies. For children with asthma falling into these categories, sensitivity was 100% (95% CI: 88-100%) and specificity 100% (95% CI: 69-100%); for children with moderate and severe rhinitis sensitivity was 93% (95% CI: 86-97%) and the specificity 100% (95% CI: 79-100%). The ImmunoCAP Rapid test is an accurate test, in particular with regard to high specificity, for diagnosing allergy in children with recurrent respiratory diseases in primary care settings.

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects.

Molecular ultrasound is capable of elucidating the expression of angiogenic markers in vivo. However, the capability of the method for volumetric "multitarget quantification" and for the assessment of antiangiogenic therapy response has rather been investigated. Therefore, we generated cyanoacrylate microbubbles linked to vascular endothelial growth factor receptor 2 (VEGFR2) and alphavbeta3 integrin binding ligands and quantified their accumulation in squamous cell carcinoma xenografts (HaCaT-ras-A-5RT3) in mice with the quantitative volumetric ultrasound scanning technique, sensitive particle acoustic quantification. Specificity of VEGFR2 and alphavbeta3 integrin binding microbubbles was shown, and changes in marker expression during matrix metalloproteinase inhibitor treatment were investigated. In tumors, accumulation of targeted microbubbles was significantly higher compared with nonspecific ones and could be inhibited competitively by addition of the free ligand in excess. Also, multimarker imaging could successfully be done during the same imaging session. Molecular ultrasound further indicated a significant increase of VEGFR2 and alphavbeta3 integrin expression during tumor growth and a considerable decrease in both marker densities after matrix metalloproteinase inhibitor treatment. Histologic data suggested that the increasing VEGFR2 and alphavbeta3 integrin concentrations in tumors during growth are related to an up-regulation of its expression by the endothelial cells, whereas its decrease under therapy is more related to the decreasing relative vessel density. In conclusion, targeted ultrasound appears feasible for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive assessment of therapy effects in vivo.

Diagnosis, Therapy and Follow-up of Vaginal Cancer and Its Precursors. Guideline of the DGGG and the DKG (S2k-Level, AWMF Registry No. 032/042, October 2018).

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Pharmacodynamics of streptavidin-coated cyanoacrylate microbubbles designed for molecular ultrasound imaging.

OBJECTIVES: To assess the pharmacodynamic behavior of cyanoacrylate, streptavidin-coated microbubbles (MBs) and to investigate their suitability for molecular ultrasound imaging. MATERIALS AND METHODS: Biodistribution of MBs was analyzed in tumor-bearing mice using gamma-counting, immunohistochemistry, flow cytometry, and ultrasound. Further, vascular endothelial growth factor receptor 2-antibody coupled MBs were used to image tumor neovasculature. RESULTS: After 1 minute >90% of MBs were cleared from the blood and pooled in the lungs, liver, and spleen. Subsequently, within 1 hour a decent reincrease of MB-concentration was observed in the blood. The remaining MBs were removed by liver and spleen macrophages. About 30% of the phagocytosed MBs were intact after 48 hours. Shell fragments were found in the kidneys only. No relevant MB-accumulation was observed in tumors. In contrast, vascular endothelial growth factor receptor 2-specific MBs accumulated significantly within the tumor vasculature (P < 0.05). CONCLUSIONS: The pharmacokinetic behavior of streptavidin-coated cyanoacrylate MBs has been studied. In this context, the low amount of MBs in tumors after >5 minutes is beneficial for specific targeting of angiogenesis.

Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain.

The role of the alpha4beta2* nicotinic acetylcholine receptors (nAChR) in tobacco addiction in humans is largely unresolved. We visualized brain alpha4beta2* nicotinic acetylcholine receptors of smokers and non-smokers with positron emission tomography using 2-[(18)F]fluoro-3-(2(S)azetidinylmethoxy)pyridine, commonly known as 2-[(18)F]F-A-85380. The total brain distribution volume of 2-[(18)F]F-A-85380 was significantly increased in smokers. Statistical parametric mapping revealed that the most prominent regional differences of distribution volumes (DV) were found in cerebellum and brainstem with an increased uptake in smokers. The up-regulation of alpha4beta2* nAChR upon chronic nicotine exposure via tobacco smoking incorporates subcortical brain regions which may play an important role in nicotine addiction.

Ultrasound basics.

Imaging technologies for in vivo functional and molecular imaging in small animals have undergone a very fast development in the last years with very intense competition to further develop resolution and molecular sensitivity. Among the imaging technologies available, ultrasound-based molecular imaging methods are of particular interest, since the use of ultrasound contrast agents allows specific and sensitive depiction of molecular targets. Together with new developments in quantification methods of targeted microbubbles, sonography represents a dynamic and seminal tool for molecular imaging.

Ultrasound contrast agents for molecular imaging.

The successful use of targeted ultrasound contrast agents (USCAs) for qualitative US-based imaging has been shown by several academic and industrial research groups in different animal models. Furthermore, techniques have been developed that enable the in-vivo quantification of targeted microbubbles (MBs). USCAs for quantitative functional and molecular imaging in small animals can be used for a more detailed characterization of new and established disease models and provide quantitative biological insights into the interaction between drug and target or target and disease in living animals. The advantages of such contrast agents in research and development are seen to be as follows: new functional or molecular findings in the complex biology of disease development, these findings can lead to new therapeutic strategies or drug candidates, a better understanding of the treatment effects of new and existing drug candidates, a more sensitive and specific characterization of early treatment effects in living animals, identification of in-vivo biomarkers for translational medicine. Further outcomes are seen in speeding up the evaluation of new drug compounds and in a reduction of the number of animals used for biomedical research.