Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal, and subcutaneous, and intravascular cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeutic-induced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9LLuc) was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI), respectively. There was excellent correlation (r=0.91) between detected photons and tumor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951). These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.

L imb girdle muscular dystrophy (LGMD) is a muscular dystrophy with predominantly proximal distribution of weakness that spares the distal, facial, and extraocular muscles early in the course of the disease. Cardiac muscle may be affected, which may manifest as hypertrophic/dilated cardiomyopathy and cardiac dysrhythmias. Significant cardiac involvement has been documented frequently in LGMD2C-F, 2I, and LGMD1B forms of the disease, rarely in the LGMD1C and 2B subtypes, and thus far have not been reported in type 2A. We report a presentation of severe cardiomyopathy in an adult with muscular dystrophy type 2A.A 23-year-old black man was seen in hospital with complaints of decreased exercise tolerance, dyspnea on exertion, orthopnea, and some presycopal episodes for several weeks.The patient's LGMD was diagnosed at the age of 21 years. No family history of similar problems was noted. Physical examination at the time revealed decreased strength in the shoulder girdle area, with inability to raise the arm over the head. Laboratory data at the time showed a creatinine kinase of 4263 U/L and serum troponin of 0.77 ng/mL. ECG revealed sinus rhythm with bifascicular block. The patient's blood was then sent for genetic testing, which demonstrated CAPN3 sequencing alteration (Athena Diagnostics, Inc).When seen by cardiology, he was noted to be alert and oriented, afebrile, and normotensive. On physical examination he was noted to have jugular venous distension, with cardiac examination significant for a grade III/VI holosystolic murmur at the left lower sternal border, with a displaced point of maximal impulse. ECG revealed normal sinus rhythm, right bundle-branch block, and left anterior fascicular block. Laboratory tests revealed a BNP of 541 pg/mL, with negative cardiac enzymes. His other laboratory tests were found to be within normal limits. An echocardiogram was notable for severely reduced right and left ventricular systolic function, left ventricular ejection fraction of 15%, severe tricuspid regurgitation, and findings suggestive of left ventricular noncompaction (Figure). The patient was treated with ACE inhibitors, β blockers, and diuretics, with no improvement in his cardiac function on subsequent echocardiography. He had few evidence to suggest possible secondary causes of his cardiomyopathy, including myocarditis and ischemic disease, although he refused more extensive testing. DiscussionSignificant cardiac involvement has been rarely documented in LGMD1C, 2A, and 2B, whereas it is relatively common in LGMD2C, 2D, 2E, 2F, 2I, and LGMD1B. This may manifest as hypertrophic/dilated cardiomyopathy and cardiac dysrhythmias.LGMD1B patients often exhibit findings of both cardiomyopathy and dysrhythmia. 1LGMD2A (calpainopathy) is found as a result of a mutation of chromosome 15 in the CAPN3 gene encoding the proteolytic enzyme calpain-3.2 Calpain-3 (p94) belongs to the calpain family of soluble intracellular cysteine proteases, the majority of which are activated by a calcium-dependent mechanism. Calpain-3 is not, ...

Background: With social attitudes about marijuana changing and patients sometimes seeking nonmainstream treatment options, the main goal of this study was to investigate the prevalence of, and factors associated with, marijuana use by patients with multiple sclerosis (MS). Methods: Adult patients with MS (n = 521) and controls (n = 279) from a study of clinical, neuroimaging, genetic, and environmental factors in MS progression were included. Patients with MS stated whether they had ever used marijuana before MS diagnosis, after MS diagnosis, and in the preceding 3 months as part of an in-person questionnaire. The control group stated whether they had ever used marijuana and in the preceding 3 months. Results: The percentage of patients with MS reporting ever use of marijuana was 39.9%, compared with 32.7% of controls. Marijuana use in the preceding 3 months was significantly more prevalent among patients with MS (9.4%) compared with controls (0.4%) (P < .001). Marijuana use was most prevalent in male patients with MS (P = .004) and in patients with MS who used complementary and alternative medicine (P = .045). Cigarette smoking was associated with marijuana use in patients with MS (P < .001) and controls (P = .001). Increasing age was associated with decreasing prevalence of marijuana use in the patients with MS (P < 0.001). Conclusions: Patients with MS are more likely to report recent marijuana use than are people without MS. Owing to potential adverse effects, marijuana use by patients with MS may warrant vigilance by MS caregivers, given shifting social attitudes and the trend towards legalization of marijuana in the United States.

Objectives This narrative review aims to synthesize information from the literature regarding older-age bipolar disorder (OABD) in order to provide up-to-date information on this important illness. Methods We searched Ovid (Medline, Embase and PsychInfo) on October 1, 2020, using the keywords “bipolar disorder”, “older adults” and “elderly” to identify relevant articles on OABD. Additionally, the bibliography of identified articles was reviewed for pertinent studies. Discussions OABD is a term that is used to describe bipolar disorder (BD) occurring amongst individuals ≥50 years of age. Evidence indicates that OABD accounts for a quarter of all cases of BD. When compared to individuals with early-onset BD, individuals with OABD have a greater association with cerebrovascular disease and other neurological disorders, less family history of mood disorders, and utilize almost four times the total amount of mental health services. In addition, they are four times more likely to have psychiatric hospitalizations when compared to age-matched controls. Despite a dearth of controlled studies on the use of pharmacotherapy amongst individuals with OABD, available evidence from mixed-age studies indicates the efficacy of commonly used medications in individuals with early-onset BD. Additionally, psychosocial treatments have been found to be effective as adjunctive management strategies amongst individuals with OABD. Furthermore, electroconvulsive therapy may be effective in the treatment of refractory cases of OABD. Conclusions There is a great need for an improved understanding of the phenomenology and neurobiology of OABD. Additionally, research into effective treatments for this serious psychiatric disorder will mitigate the suffering of individuals with OABD.