Chronic DMI reduces thresholds for brain stimulation reward in the rat

The authors sought a demonstration of the validity of brain stimulation reward (BSR) models of depression. It was predicted that chronic, but not acute antidepressant treatment would enhance BSR responding. Rats with medial forebrain bundle electrodes were separated into 4 groups that received either saline or desmethylimipramine at 5, 10, or 20 mg/kg daily. A rate-free, threshold measure that has not previously been employed in studies of BSR and antidepressants was used. BSR thresholds were monitored every 3rd day over a 9-day baseline period and an 18-day drug treatment period, and after 12 days of drug withdrawal. Groups did not differ from one another till the 15th and 18th day of drug treatment. The greatest effects were seen in the 10 and 20 mg groups. The 20 mg group returned to baseline after drug withdrawal, but the 10 mg group did not. The absolute size of the effect was considered to be small, leading the authors to speculate that antidepressants act on homeostatic mechanisms that stabilize BSR substrates, only indirectly enhancing transmission of the reward signal.     

Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum

The aim of this Phase I/IIa double-blind controlled trial was to test the efficacy of the sporozoite-based malaria vaccine PfCS 282–383 (PfCS102) to protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized to receive twice 30 μg of PfCS102 formulated in Montanide ISA 720 or ISA 720 alone (control). Two weeks after 2nd immunization, volunteers were challenged using 5 infected mosquitoes. All vaccinees developed antibodies against PfCS102 versus none control. 8/8 vaccinees and 6/6 controls challenged developed malaria parasitaemia. The duration from infection to onset of patent parasitaemia was similar in both groups (214 h in vaccinees and 216 in controls). PfCS102 is safe and immunogenic but provides no protection against artificial challenge in its current formulation.     

Bowel endometriosis: CT-enteroclysis

Although several radiological techniques have been used for the diagnosis of bowel endometriosis, no gold standard is currently established. We used multislice computerized tomography (CT) combined with the distention of the colon by rectal enteroclysis (MSCTe) for the diagnosis of bowel endometriosis. Following bowel preparation, pharmacological hypotonicity, retrograde colonic distention by water enteroclysis, and intravenous injection of iodinated contrast medium, a single volumetric acquisition of the abdomen is performed. MSCTe findings suggestive of bowel endometriosis are the presence of solid nodules with positive enhancement, contiguous or penetrating the colonic wall. When endometriotic lesions are detected, the degree of infiltration of the intestinal wall can be estimated; however, the depth infiltrated by nodules reaching the submucosa may be underestimated. MSCTe is well tolerated by the patients. The strength of MSCT consists in the high spatial resolution; volumetric data acquired by using thin slices provide isotropic voxels and multiplanar reconstructions have a quality comparable with that of the original axial scans. The potential of MSCTe for the diagnosis of bowel endometriosis relies on the fact that the serosal, muscular, and mucosal layers of the bowel wall can be evaluated.     

Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio Are Not Prognostic Biomarkers in Rectal Cancer Patients with Curative Resection

Background

Actual predictors of survival and recurrence for rectal cancer patients undergoing curative resection mostly come from pathological data of surgical specimen. Recently, novel blood biomarkers have been proposed as useful tools in cancer patient management, but few and conflicting data have been reported in rectal cancer. We evaluated the prognostic relevance of preoperative platelet-to-lymphocyte (P/L) ratio and neutrophil-to-lymphocyte (N/L) ratio on survival and recurrence in patients undergoing laparoscopic curative resection for rectal cancer.

Methods

All consecutive patients who referred for primary rectal disease to the Department of General Surgery in Cittadella (Italy) from June 2005 to September 2015 were retrospectively evaluated. Patients with metastatic disease at surgery were excluded. P/L and N/L ratios were calculated. For patients undergoing neoadjuvant chemo-radiotherapy, pre-treatment data were considered. Follow-up data were updated at December 2016.

Results

One hundred fifty-two patients were included in the study, 49 (32%) received neoadjuvant chemo-radiotherapy. Both P/L and N/L ratios showed poor discriminative performance on 5-year OS and DFS. Time-dependent ROC curves showed no improvements in discriminative performance of P/L and N/L ratios when considering different time endpoints. Multivariable analysis identified CEA—rather than P/L or N/L ratios—as independent predictor of OS and DFS, adjusting for age, tumor stage, and postoperative morbidity.

Conclusion

Neither P/L nor N/L ratios were associated with survival after rectal cancer surgery. Further studies on large series might provide insights on the role of these inexpensive blood biomarkers in rectal cancer.

     

Evaluation of a 2D UNet-Based Attenuation Correction Methodology for PET/MR Brain Studies

Journal of Digital Imaging - Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps,...     

New Fluorescent Probes Targeting the Mitochondrial-Located Translocator Protein 18 kDa (TSPO) as Activated Microglia Imaging Agents

Purpose  

To evaluate the utility of new Translocator protein 18 kDa (TSPO)-targeted fluorescent probes for in vivo molecular imaging of activated microglia.     

Corticotropin-Releasing Factor in the Norepinephrine Nucleus,Locus Coeruleus,Facilitates Behavioral Flexibility

Corticotropin-releasing factor (CRF), the stress-related neuropeptide, acts as a neurotransmitter in the brain norepinephrine nucleus, locus coeruleus (LC), to activate this system during stress. CRF shifts the mode of LC discharge from a phasic to a high tonic state that is thought to promote behavioral flexibility. To investigate this, the effects of CRF administered either intracerebroventricularly (30–300 ng, i.c.v.) or directly into the LC (intra-LC; 2–20 ng) were examined in a rat model of attentional set shifting. CRF differentially affected components of the task depending on dose and route of administration. Intracerebroventricular CRF impaired intradimensional set shifting, reversal learning, and extradimensional set shifting (EDS) at different doses. In contrast, intra-LC CRF did not impair any aspect of the task. The highest dose of CRF (20 ng) facilitated reversal learning and the lowest dose (2 ng) improved EDS. The dose–response relationship for CRF on EDS performance resembled an inverted U-shaped curve with the highest dose having no effect. Intra-LC CRF also elicited c-fos expression in prefrontal cortical neurons with an inverted U-shaped dose–response relationship. The number of c-fos profiles was positively correlated with EDS performance. Given that CRF excites LC neurons, the ability of intra-LC CRF to activate prefrontal cortical neurons and facilitate EDS is consistent with findings implicating LC-norepinephrine projections to medial prefrontal cortex in this process. Importantly, the results suggest that CRF release in the LC during stress facilitates shifting of attention between diverse stimuli in a dynamic environment so that the organism can adapt an optimal strategy for coping with the challenge.     

The long pentraxin 3 is a soluble and cell-associated component of the human semen

The long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition receptor, involved in several processes ranging from innate resistance and inflammation to clearance of apoptotic cells and organization of hyaluronic acid-rich extracellular matrices. PTX3 is also a novel marker in several pathological conditions of infectious, inflammatory, or autoimmune origin. This study was designed to assess whether PTX3 is expressed in the male reproductive tract and whether PTX3 interacts with human spermatozoa influencing their function. Here we show for the first time by immunohistochemistry that PTX3 is expressed in the male genital tract in perivascular connective tissue, in endothelial cells, in the interstitium, and in the cytoplasm of prostatic epithelial glandular cells; PTX3 was detectable in seminal plasma in variable levels, which correlated with the percentage of normal spermatozoa. Moreover, PTX3 binds to spermatozoa, in particular with immotile cells, localizing in the neck and in the subacrosomial region. Finally, recombinant PTX3 did not interfere with sperm motility.