Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use. EXPERIMENTAL DESIGN: We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficient mice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[(11)C]methyl-L-cysteine ([(11)C]DCMC K(i), 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-L-tyrosine ([(125)C]DCIT K(i), 1.5 nmol/L) were synthesized using [(11)C]CH(3)I and with [(125)I]NaI/Iodogen, respectively.RESULTS: At 30 minutes postinjection, [(11)C]DCMC and [(125)I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [(11)C]DCMC or [(125)I]DCIT. CONCLUSION: These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.     

A nucleic acid amplification test‐based strategy does not help inform return to work for healthcare workers with COVID‐19

ObjectiveThe objective of this study is to assess the utility of a nucleic acid amplification test‐based approach to shorten isolation of healthcare workers (HCWs) with COVID‐19 in the setting of the highly transmissible omicron variant.MethodsBetween December 24, 2021, and January 5, 2022, HCWs who tested positive for SARS‐CoV‐2 were retested with PCR at least 5 days since onset of symptoms.ResultsForty‐six sequential fully COVID‐19 vaccinated HCWs who had tested positive for SARS‐CoV‐2 underwent follow‐up testing. All the samples were confirmed as omicron variants and only four (8.7%) were negative in the follow‐up test performed at a median of 6 (range 5–12) since onset of symptoms.ConclusionsImplementation of a test‐based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution.     

Regulating a novel drug: An evaluation of changes in use of Salvia divinorum in the first year of Florida's ban

BackgroundA plant with dissociative and psychoactive properties began to attract the attention of the media and United States policymakers following a well-publicized suicide in 2006 and reports that the plant served as a ‘legal high’ and substitute for cannabis. As a result, Salvia divinorum and its active ingredient, salvinorin A, were classified as Schedule I substances by the Florida Legislature on July 1, 2008. As of yet, no research has explored the efficacy of this policy or similar policies in other jurisdictions.MethodsThree self-report studies collected from young adults both prior to and following the policy's implementation are employed to investigate the potential relationship between the policy and usage rates. In addition, law enforcement personnel from the state's most populated areas were interviewed to determine the extent to which they were encountering salvia in their work.ResultsIt was indicated that less than two-thirds of those surveyed were aware of the drug's legal status. Lifetime prevalence of salvia use was largely unchanged. However, the rates of self-reported past year and past month use in Florida were significantly lower following the scheduling. Though use of Salvia divinorum appears to have decreased, perceptions of peer use increased markedly. Law enforcement officers and laboratories reported rarely, if ever, dealing with cases of salvia possession.ConclusionsData suggests the classification of Salvia divinorum as a Schedule I drug was followed by a substantial reduction in recreational use. We caution that other factors may have influenced use, that the efficacy of scheduling novel substances is likely to vary by drug type, that such a reduction in reported use may only exist transiently until a sophisticated illicit market develops to replace the legitimate one, and that a state's success in regulating salvia may be related to their regulation of and enforcement of other drug prohibitions.     

Book Review

The relationship between variation in wood shrinkage and cellulose crystallite width determined by X-ray diffraction was assessed using SilviScan-2 (a system developed at CSIRO for rapid assessment of wood microstructure). Cellulose crystallite width, density and microfibril angle were determined for 600μm wide zones on small wood samples with known tangential shrinkage. The tangential shrinkage measurements included shrinkage to 12% moisture content after reconditioning (MC AR); and a shrinkage differential calculated from tangential shrinkage to 12% MC AR recorded for each zone; and the minimum shrinkage recorded in adjacent wood of similar cambial age. Spearman correlations and forward stepwise regressions showed that the cellulose crystallite width was a good predictor of the shrinkage measures and that density was a minor predictor. Together, cellulose crystallite width and density could explain 75% of the variation in tangential shrinkage for randomly selected locations throughout the tree, and 87% of the variation in tangential shrinkage in samples selected from the lower 5% of tree height. The results suggest that SilviScan-2 can be used to predict tangential shrinkage during drying in increment cores, and may therefore be useful in developing nondestructive sampling strategies in tree improvement programs for E. globulus.     

Physiological and psychological responses to a 12-week BodyBalance training programme

BodyBalance is a popular mind–body program practised at numerous leisure centres throughout the western world that makes many unsubstantiated claims as to the benefits of participation. This study examines physiological and psychological responses in adults, aged (mean ± S.D.) 43.9 ± 10.9 years, to a 12-week ‘BodyBalance’ exercise program. An exercise intervention group (n = 17) undertook three 1-h classes, each week for 12 consecutive weeks while the control group (n = 17) attended three 90-min ‘health lectures’. ANCOVA demonstrated significant differences between the control and exercise groups in body mass, skinfold measures, total girth circumference from six sites, maximal isometric back strength, five measures of flexibility and state anxiety. Post-hoc tests on the experimental group data showed body fat decreased significantly by 1.10 ± 1.02% (t = 4.44; P < 0.01), girth by 4.40 ± 5.80 cm (t = 3.13; P < 0.01) and back strength increased by 17.12 ± 15.39 kgf (t = −4.59; P < 0.01). Flexibility was also significantly enhanced with performance of the modified sit-and-reach test increasing by 5.90 ± 2.56 cm (t = −9.50; P < 0.01), hip flexion by 9.84 ± 8.41° (t = −4.82; P < 0.01), hip extension by 7.65 ± 4.48° (t = −7.04; P < 0.01), hip abduction by 10.00 ± 4.91° (t = −8.40; P < 0.01) and lateral trunk flexion by 3.06 ± 5.72° (t = −2.21; P < 0.05). Finally, state-anxiety (STAI) was significantly reduced intra-class at weeks 1, 6 and 12 by 9.24 ± 9.46 (t = 4.02; P < 0.01), 6.59 ± 6.26 (t = 4.34; P < 0.01) and 7.18 ± 5.50 (t = 5.38; P < 0.01), respectively. The findings of this study suggest mind–body exercise programs like BodyBalance could significantly benefit state-anxiety as well as strength, flexibility, and anthropometry around the trunk.     

Intra abdominal hypertension and the abdominal compartment syndrome

The patho-physiological significance of raised intra-abdominal pressure, known as Intra Abdominal Hypertension, with subsequent organ dysfunction and failure, known as Abdominal Compartment Syndrome, has recently been demonstrated to occur relatively frequently in mixed populations of critically ill patients. Clinical diagnosis is unreliable, so routine measurement of intra abdominal pressure should be undertaken, particularly in specific groups of patients known to be at high risk. Whilst definitive therapy requires surgical abdominal decompression, less invasive therapies have been investigated and, if initiated early, may help to minimise progression of the condition. Clearly defined indications for surgical intervention remain elusive however and require prospective investigation. This review summarises the patho-physiology of the syndrome, its diagnosis and surveillance, and current management strategies, both medical and surgical.     

Social support, ethnicity and mental health in adolescents

Objective In this study, we explored whether social support varied with ethnic group in young people, and if it explained ethnic differences in prevalence of psychological distress. Methods A representative sample of 2790 East London adolescents (11–14 years) completed a classroom-based self-report questionnaire for this cross sectional survey. Social support was assessed using the Multidimensional Scale of Perceived Social Support (MSPSS). Mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ) and the Short Moods and Feelings Questionnaire (SMFQ). Results High levels of social support were reported by most participants, with some variation by ethnic group and gender. Participants reporting low family and overall social support had an increased likelihood of psychological distress compared with those who reported high support. Low support from friends, family and overall was also associated with depressive symptoms. These relationships did not alter with adjustment for ethnic group. Conclusions This study identified an independent association between different sources of social support and mental health in a young, ethnically diverse sample. Differences in social support did not explain ethnic differences in psychological distress.