Questioning a “Compulsory Ontology of Pathology” Regarding Suicide and the Suicidal

The death of a neonate can be traumatic for mothers, resulting in profound grief, which ruptures their sense of coherence and identity. A narrative approach was used to explore how six Xhosa-speaking women tell stories about the death of their baby to help them understand the significance of the loss. They struggled to establish a sense of their baby as a person to be mourned, to redefine their own identity, and to find reasons for the death. Their meaning-making was influenced by the baby's father, older women in their community, and the context of deprivation in which they live.     

The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma

Current knowledge about molecular mechanisms underlying disease progression and drug resistance in multiple myeloma (MM) is still limited. Here, we analyzed the potential pathogenetic role of the Y-box binding protein YB-1 in MM. YB-1 is a member of the cold-shock domain protein superfamily and involved in various cellular functions such as proliferation. Immunohistochemical analyses revealed that neither normal bone marrow (BM) plasma cells (PCs), premalignant PCs of patients with monoclonal gammopathy of unknown significance (MGUS), nor MM cells with a mature morphology showed expression of YB-1 in situ. In contrast, YB-1 was strongly expressed in situ in normal PC precursor blasts as well as in a MM subset and in vitro in all of the evaluated MM cell lines. The YB-1-expressing MM cells were characterized by an immature morphology and a highly proliferative phenotype as defined by Ki 67 expression. We observed that siRNA-mediated knockdown of YB-1 decreased proliferation and induced apoptosis in MM cells even in the presence of BM stromal cells. Furthermore, we found that overexpression of YB-1 mediated resistance toward doxorubicin-induced apoptosis in MM cells. Thus, YB-1 contributes to disease progression, survival, and drug resistance in MM and might therefore provide an attractive therapeutic target.     

Peroxisome proliferator-activated receptor-gamma protects against hepatic ischemia/reperfusion injury in mice

The function of peroxisome proliferator-activated receptor-gamma (PPARgamma) in hepatic inflammation and injury is unclear. In this study, we sought to determine the role of PPARgamma in hepatic ischemia/reperfusion injury in mice. Male mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 8 hours of reperfusion. PPARgamma was found to be constitutively activated in hepatocytes but not in nonparenchymal cells. Upon induction of ischemia, hepatic PPARgamma activation rapidly decreased and remained suppressed throughout the 8-hour reperfusion period. This reduced activation was not a result of decreased protein availability as hepatic nuclear PPARgamma, retinoid X receptor-alpha (RXRalpha), and PPARgamma/RXRalpha heterodimer expression was maintained. Accompanying the decrease in PPARgamma activation was a decrease in the expression of the natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). This was associated with reduced interaction of PPARgamma and the coactivator, p300. To determine whether PPARgamma activation is hepatoprotective during hepatic ischemia/reperfusion injury, mice were treated with the PPARgamma agonists, rosiglitazone and connecting peptide. These treatments increased PPARgamma activation and reduced liver injury compared to untreated mice. Furthermore, PPARgamma-deficient mice had more liver injury after ischemia/reperfusion than their wild-type counterparts. Conclusion: These data suggest that PPARgamma is an important endogenous regulator of, and potential therapeutic target for, ischemic liver injury.     

Ectopic thyroid gland in the porta hepatis and lingua.

A rare case of an ectopic thyroid gland in the porta hepatis and in the tongue in an asymptomatic euthyroid 24-year-old woman is reported. A solitary inhomogeneous, hypoechogenic and hyperechogenic mass in the porta hepatis was accidentally discovered by ultrasonography. Subsequent computed tomography demonstrated a heterogeneous, well-defined tumor with small calcifications without signs of environmental invasion. A hemangioma and focal nodular hyperplasia were excluded by blood pool and hepatobiliary scintigraphy. Surprisingly, fine-needle aspiration cytology revealed normal thyroid tissue. (123)I-scintigraphy confirmed the presence of ectopic dual thyroid tissue in the hepatic porta and lingua. At clinical inspection the lingual thyroid gland was palpable and visible, and appeared solid and spheroidal. The subhepatic, ectopic thyroid mass was resected. Postoperatively, thyroid hormone replacement was started to prevent an enlargement of the lingual thyroid. Today, 4 years after surgery, the patient remains euthyroid.     

Insufficient tissue ablation by rotational atherectomy leads to worse long-term results in comparison with balloon angioplasty alone for the treatment of diffuse in-stent restenosis: insights from the intravascular ultrasound substudy of the ARTIST randomized multicenter trial.

The ARTIST trial demonstrated a worse outcome for patients with in-stent restenosis (ISR) treated with rotational atherectomy (RA) and adjunctive balloon angioplasty (PTCA) as compared to PTCA alone. This intravascular ultrasound (IVUS) substudy compares effects of lumen enlargement and examines reasons for failure of RA in this setting. IVUS (n = 56) was performed after each interventional step and at follow-up. Volumetric lumen gain measured 79 +/- 68 mm(3) after PTCA (13 +/- 4 atm) as compared to 44 +/- 26 mm(3) after RA and adjunctive PTCA (7 +/- 3 atm; P < 0.0001). RA itself enlarged lumen by only 19 +/- 17 mm(3) and stent volume was 47% smaller as compared to high-pressure PTCA. Low-pressure strategy after RA did not prevent tissue growth during follow-up (19 +/- 25 vs. 36 +/- 38 mm(3); RA vs. PTCA; P = 0.09). Consequently, net lumen gain after PTCA was 82% higher compared to RA (46 +/- 54 vs. 25 +/- 24 mm(3); P = 0.09). Further stent expansion is the key mechanism to achieve luminal gain by PTCA of ISR. Neointimal ablation by RA has only minor effects. Low-pressure PTCA does not prevent recurrent tissue growth and failed for treatment of ISR due to insufficient stent expansion.     

Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation

A phase 1 diagnostic study was performed to evaluate a novel technology for clinical proteomic research based on capillary electrophoresis and mass spectrometry. Urine from 40 patients after hematopoietic stem cell transplantation (HSCT; 35 allogeneic, 5 autologous) and 5 patients with sepsis was collected for a period of 100 days and analyzed. More than 1000 different polypeptides could be detected in individual samples. Polypeptide patterns excreted in the urine of patients were significantly different from those of healthy volunteers. No significant differences were detected comparing different conditioning regimens. The aim of this study was to identify polypeptide patterns functioning as early indicators of graft-versus-host disease (GVHD). Eighteen patients developed GVHD after allogeneic HSCT. Sixteen differentially excreted polypeptides formed a pattern of early GVHD markers, allowing discrimination of GVHD from patients without complications with 82% specificity and 100% sensitivity, cross-validated. Inclusion of 13 sepsis-specific polypeptides allowed us to distinguish sepsis from GVHD with a specificity of 97% and a sensitivity of 100%. Sequencing 2 prominent GVHD-indicative polypeptides led to the identification of a peptide from leukotriene A4 hydrolase and a peptide from serum albumin. The data reveal that capillary electrophoresis and mass spectrometry allow identification of biomarkers for a variety of diseases or related complications.     

Imaging Characteristics and First Experience of [<Superscript>68</Superscript>Ga]THP-PSMA,a Novel Probe for Rapid Kit-Based Ga-68 Labeling and PET Imaging: Comparative Analysis with [<Superscript>68</Superscript>Ga]PSMA I&amp;T

Purpose

[⁶⁸Ga]Trishydroxypyridinone (THP)–prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [⁶⁸Ga]THP-PSMA.

Procedures

[⁶⁸Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [⁶⁸Ga]PSMA I&T.

Results

Physiologic uptake of [⁶⁸Ga]THP-PSMA was significantly lower in salivary glands (P?<?0.0001), liver (P?<?0.0001), spleen (P?<?0.0001), and kidneys (P?<?0.0001) than with [⁶⁸Ga]PSMA I&T. While biliary tracer excretion of [⁶⁸Ga]THP-PSMA was negligible, urinary tracer excretion of [⁶⁸Ga]THP-PSMA was fast, and significantly higher than for [⁶⁸Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [⁶⁸Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [⁶⁸Ga]PSMA I&T.

Conclusion

[⁶⁸Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [⁶⁸Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [⁶⁸Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.

     

Comparison of two dietary assessment methods by food consumption: results of the German National Nutrition Survey II

Purpose

To further characterise the performance of the diet history method and the 24-h recalls method, both in an updated version, a comparison was conducted.

Methods

The National Nutrition Survey II, representative for Germany, assessed food consumption with both methods. The comparison was conducted in a sample of 9,968 participants aged 14–80. Besides calculating mean differences, statistical agreement measurements encompass Spearman and intraclass correlation coefficients, ranking participants in quartiles and the Bland–Altman method.

Results

Mean consumption of 12 out of 18 food groups was higher assessed with the diet history method. Three of these 12 food groups had a medium to large effect size (e.g. raw vegetables) and seven showed at least a small strength while there was basically no difference for coffee/tea or ice cream. Intraclass correlations were strong only for beverages (>0.50) and revealed the least correlation for vegetables (<0.20). Quartile classification of participants exhibited more than two-thirds being ranked in the same or adjacent quartile assessed by both methods. For every food group, Bland–Altman plots showed that the agreement of both methods weakened with increasing consumption.

Conclusions

The cognitive effort essential for the diet history method to remember consumption of the past 4 weeks may be a source of inaccurateness, especially for inhomogeneous food groups. Additionally, social desirability gains significance. There is no assessment method without errors and attention to specific food groups is a critical issue with every method. Altogether, the 24-h recalls method applied in the presented study, offers advantages approximating food consumption as compared to the diet history method.