Patterns of autobiographical memory loss in medial-temporal lobe amnesic patients

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of one's personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.     

The Bluetongue Disabled Infectious Single Animal (DISA) Vaccine Platform Based on Deletion NS3/NS3a Protein Is Safe and Protective in Cattle and Enables DIVA

The bluetongue virus (BTV) is transmitted by Culicoides biting midges and causes bluetongue (BT), an OIE-notifiable disease of ruminants. At least 29 BTV serotypes are described as determined by the outer shell proteins VP2 and VP5. Vaccination is the most effective control measure. Inactivated and live-attenuated vaccines (LAVs) are currently available. These vaccines have their specific pros and cons, and both are not DIVA vaccines. The BT Disabled Infectious Single Animal (DISA) vaccine platform is based on LAV without nonessential NS3/NS3a expression and is applicable for many serotypes by the exchange of outer shell proteins. The DISA vaccine is effective and completely safe. Further, transmission of the DISA vaccine by midges is blocked (DISA principle). Finally, the DISA vaccine enables DIVA because of a lack of antibodies against the immunogenic NS3/NS3a protein (DIVA principle). The deletion of 72 amino acids (72aa) in NS3/NS3a is sufficient to block virus propagation in midges. Here, we show that a prototype DISA vaccine based on LAV with the 72aa deletion enables DIVA, is completely safe and induces a long-lasting serotype-specific protection in cattle. In conclusion, the in-frame deletion of 72-aa codons in the BT DISA/DIVA vaccine platform is sufficient to fulfil all the criteria for modern veterinary vaccines.     

The long-term sealing ability of AH 26 and AH plus used with three gutta-percha obturation techniques.

OBJECTIVE: To evaluate and compare the sealability of root fillings in extracted teeth by using AH 26 and AH Plus in conjunction with three different obturation techniques. METHOD AND MATERIALS: Root canals of 940 single-rooted teeth were prepared according to the crown-down/stepback technique (using both 2.5% NaOCl and File-Eze) before lateral condensation and hybrid condensation of gutta percha or obturation with Thermafil. Teeth were immersed in India ink for 90 hours after storage for 1 day, 1 week, 2 weeks, 1 month, and 6 months. The roots were split longitudinally, and the extent of dye penetration was measured using a stereomicroscope. Statistical analysis was performed using Kruskal-Wallis test and Mann-Whitney U test. RESULTS: There were no statistically significant differences in apical leakage within the AH 26 and the AH Plus groups, nor between the two sealer groups, at any observation period. Coronal leakage was significantly higher for Thermafil compared to hybrid condensation at 1 day, 1 week, and 2 weeks both for AH 26 and AH Plus. Coronal leakage was higher only for Thermafil compared to lateral condensation at 1 week for AH 26 and for lateral condensation compared to hybrid condensation at 1 week for AH Plus. CONCLUSION: Both AH 26 and AH Plus, when used with an identical gutta-percha obturation technique, resulted in comparable sealability at all evaluation times and in comparable coronal sealability at 1 and 6 months.     

T2 quantifications of lungs in the fetal lamb with experimentally-induced congenital diaphragmatic hernia

OBJECTIVE: As an aid to evaluate lung hypoplasia, we investigated the difference between T2 value in fetal lungs of lambs with surgically-induced left-sided diaphragmatic hernia (DH) and gestational age (GA)-matched control littermates (normal [NL]). METHODS: Lungs were divided into two groups: DH (n = 4) and NL (n = 6). DH was induced at 65-75 days GA (term = 145 days). Fetal MRI was performed (mean GA: 120 days) with half-Fourier acquisition single-shot turbo spin-echo (TE: 60 ms) and rapid acquisition with relaxation enhancement (TE: 350 ms) in the same location (1.5-T Philips, Gyroscan, Best, The Netherlands). T2 of each lung was calculated for multiple regions of interest by taking natural logarithm of signal-to-noise ratio. Mean T2 was compared between DH and NL (unpaired analysis for entire group). Paired comparison between left/right lung was made within DH and NL. RESULTS: Unpaired analysis showed significantly lower T2 of left respectively right lungs in DH (p = 0.02 [respectively] 0.05]) compared to NL (n = 6), as well as between the T2 of all DH versus NL (p = 0.001). In DH, calculated T2 appeared to be lower in left than in right lungs (difference ranged from -2 to +49%). In NL, left and right lungs showed comparable T2. CONCLUSION: Measurement of T2 signal intensity in DH lungs is feasible and show lower T2 in comparison to NL lungs. Left lungs from lambs with DH show lower T2 than right lungs.     

Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment

We investigated the potential of tumor-infiltrating immune cells (ICs) as predictive or prognostic biomarkers for cervical cancer patients. In total, 38 patients treated with (chemo)radiotherapy and subsequent surgery were included in the current study. This unique treatment schedule makes it possible to analyze IC markers in pretreatment and posttreatment tissue specimens and their changes during treatment. IC markers for T cells (CD3, CD4, CD8 and FoxP3), macrophages (CD68 and CD163) and B cells (CD20), as well as IL33 and PD-L1, were retrospectively analyzed via immunohistochemistry. Patients were grouped in the low score or high score group based on the amount of positive cells on immunohistochemistry. Correlations to pathological complete response (pCR), cause-specific survival (CSS) and metastasis development during follow-up were evaluated. In analysis of pretreatment biopsies, significantly more pCR was seen for patients with CD8 = CD3, CD8 ≥ CD4, positive IL33 tumor cell (TC) scores, IL33 IC < TC and PD-L1 TC ≥5%. Besides patients with high CD8 scores, also patients with CD8 ≥ CD4, CD163 ≥ CD68 or PD-L1 IC ≥5% had better CSS. In the analysis of posttreatment specimens, less pCR was observed for patients with high CD8 or CD163 scores. Patients with decreasing CD8 or CD163 scores between pretreatment and posttreatment samples showed more pCR, whereas those with increasing CD8 or decreasing IL33 IC scores showed a worse CSS. Meanwhile, patients with an increasing CD3 score or stable/increasing PD-L1 IC score showed more metastasis during follow-up. In this way, the intratumoral IC landscape is a promising tool for prediction of outcome and response to (chemo)radiotherapy.     

Prenatal diagnosis, prediction of outcome and in utero therapy of isolated congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) can be associated with genetic or structural anomalies with poor prognosis. In isolated cases, survival is dependent on the degree of lung hypoplasia and liver position. Cases should be referred in utero to tertiary care centers familiar with this condition both for prediction of outcome as well as timed delivery. The best validated prognostic indicator is the lung area to head circumference ratio. Ultrasound is used to measure the lung area of the index case, which is then expressed as a proportion of what is expected normally (observed/expected LHR). When O/E LHR is < 25% survival chances are < 15%. Prenatal intervention, aiming to stimulate lung growth, can be achieved by temporary fetal endoscopic tracheal occlusion (FETO). A balloon is percutaneously inserted into the trachea at 26-28 weeks, and reversal of occlusion is planned at 34 weeks. Growing experience has demonstrated the feasibility and safety of the technique with a survival rate of about 50%. The lung response to, and outcome after FETO, is dependent on pre-existing lung size as well gestational age at birth. Early data show that FETO does not increase morbidity in survivors, when compared to historical controls. Several trials are currently under design.     

Results of an endocrinological follow-up of patients with childhood-or adolescent-onset malignancies

BACKGROUND: Established reports about endocrine follow-ups in children and adolescents with cancer were rare. PATIENTS: 53 children were included in the clinical trial. The mean age was 9.6 years (0.5; 17.2 years), 10 patients died within the study period. The mean body length was normal with -0.14 SDS (-2.3; 2.5 SDS), as well as the body weight with 0.01 SDS and BMI with a mean of -0.03 SDS. Children and adolescents with different types of malignant tumors were included. According to the therapy protocol or tumor entity we divided this population in 5 subgroups (group 1 leukemia with 17 patients, group 2 lymphoma with 11 patients, group 3 tumor of CNS with 10 patients, group 4 bone and soft tissue tumors with 8 patients, group 5 different tumors with 7 patients). METHOD: Anthropometrical and laboratory parameters were analyzed in intervals of 6 months over 2 years from the time point of diagnosis. RESULTS: We found differences in body height in children affected by cerebral tumors at the time of diagnosis and therefore before any therapy was started. These patients were significantly shorter (-0.6 SDS) than the other children. The body weight increased within the first year of therapy and was still higher than normal in the second year (comparison at the time point; from start to the first year+0.5 SDS, to second year+0.4 SDS) independently from the cortisone administration. Moreover, significant differences in the growth factor concentrations between the groups and time points were identified. Interestingly, children who survived their malignant disease tended to have higher levels of IGF-I and IGFBP-3 concentration than the patients who died within the study period. Additionally, the thyroid function was affected, shown as an increase of TSH with a concomitant decrease of the free thyroxin in 91% of all patients independent from the diagnosis (start TSH 1.8, fT4 15.6, after first year TSH 2.8, fT4 15.0). Thyroid function was monitored in 12 children, in 5 patients a short- or long-term substitution with thyroid hormone was indicated. Endocrine testing was initiated in 4 children, in 2 patients affection of the adrenal gland could be excluded, a suspected pituitary dysfunction after radiation was confirmed in 2 patients. CONCLUSION: We could represent that children and adolescents with malignant diseases showed affection of the endocrine system due to the tumour and the intensive therapy. The dysregulations in the endocrine system can be diagnosed through closely spaced monitoring and interdisciplinary cooperation.     

New markers for old stains: stable mRNA markers for blood and saliva identification from up to 16-year-old stains

In forensic science, the unequivocal identification of the cellular origin of crime scene samples used for DNA profiling can provide crucial information for crime scene reconstruction. We have previously shown that various mRNA markers from genes with expression patterns specific for blood and saliva can be established from whole-genome expression analysis of time-wise degraded samples and were stable enough to specifically identify blood and saliva stains up to 180 days of age. Here, we showed that nine blood-specific and five saliva-specific mRNA markers can be amplified successfully and reliably in much older blood (13–16 years) and saliva (2–6 years) stains, respectively, suggesting their suitability for tissue identification in forensic case work. Moreover, our findings imply that forensic RNA testing can be reliable and robust if degraded samples are considered in the marker ascertainment procedure, with promising expectations beyond tissue identification purposes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Miscellaneous  The gene name SPRR3 needs to be replaced by SPRR2A in our previous publication Zubakov et al. Int J Legal Med 122(2):135–142, 2008.