Brainstem system of hippocampal theta induction: The role of the ventral tegmental area

This article summarizes the results of studies concerning the influence of the ventral tegmental area (VTA) on the hippocampal theta rhythm. Temporary VTA inactivation resulted in transient loss of the hippocampal theta. Permanent destruction of the VTA caused a long‐lasting depression of the power of the theta and it also had some influence on the frequency of the rhythm. Activation of glutamate (GLU) receptors or decrease of GABAergic tonus in the VTA led to enhancement of dopamine release and increased hippocampal theta power. High time and frequency cross‐correlation was detected for the theta band between the VTA and hippocampus during paradoxical sleep and active waking. Thus, the VTA may belong to the broad network involved in theta rhythm regulation. This article also presents a model of brainstem–VTA–hippocampal interactions in the induction of the hippocampal theta rhythm. The projections from the VTA which enhance theta rhythm are incorporated into the main theta generation pathway, in which the septum acts as the central node. The neuronal activity that may be responsible for the ability of the VTA to regulate theta probably derives from the structures associated with rapid eye movement (sleep) (REM) sleep or with sensorimotor activity (i.e., mainly from the pedunculopontine and laterodorsal tegmental nuclei and also from the raphe). Synapse 69:553–575, 2015 . © 2015 Wiley Periodicals, Inc.     

Prion diseases: a dual view of the prion hypothesis as seen from a distance

We review the historical background and principles of the prion theory in its current shape. We showed that most of data may be still interpreted dually according to the protein only hypothesis and according to the theory in which additional component is necessary to comprise the infectivity. The enormous impact of structural biological studies is also stressed.     

Sleep disturbances in women with polycystic ovary syndrome

Sleep disturbances in women with Polycystic Ovary Syndrome (PCOS) have been reported in recent years. The majority of published studies are related to Obstructive Sleep Apnea (OSA) while not many researches have analyzed any other causes of sleep disturbances. A group of ninety five women with Polycystic Ovary Syndrome were enrolled into the study. Sleep disturbances were assessed using validated questionnaires. On the grounds of Athens Insomnia Scale (AIS) evaluation a clinically significant insomnia was ascertained in 12.6% of women with PCOS, while according to Insomnia Severity Index (ISI) in 10.5%. Clinically significant insomnia according to both AIS and ISI, occurred significantly more often in women with PCOS than in women without PCOS based on the chi-square test. The Mann–Whitney U test revealed statistically significant difference between women with and without PCOS based on total values of ISI. An excessive daytime sleepiness occurred at 7.4% of women with PCOS. Statistically significant dependance between: clinically significant insomnia in both AIS and ISI and excessive daytime sleepiness indicated by Epworth Sleepiness Scale (ESS) was observed. Sleep disorders are common in women with PCOS. Screening assessment of sleep disturbances should be a part of medical diagnostics in women with PCOS.     

Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer's disease

Plasma alpha beta levels have been examined in sporadic Alzheimer's disease yielding conflicting results; both no difference and an increase in plasma concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as compared to controls have been reported. Elevated plasma alpha beta42 levels may be detected several years before the onset of symptoms (in mild cognitive impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a commercially available ELISA. Mean plasma alpha beta42 levels were significantly higher in MCI as compared to both AD (P < 0.001) and control subjects (P < 0.001), while alpha beta40 did not differ between the groups. No correlations were observed between alpha beta levels and age, MMSE scores or gender. According to ROC curve analysis the maximum accuracy in discriminating MCI versus both controls and AD subjects has been achieved using a cut-off value of 3.8.     

Verification of the exponential model of body temperature decrease after death in pigs

The authors have conducted a systematic study in pigs to verify the models of post-mortem body temperature decrease currently employed in forensic medicine. Twenty-four hour automatic temperature recordings were performed in four body sites starting 1.25 h after pig killing in an industrial slaughterhouse under typical environmental conditions (19.5-22.5 degrees C). The animals had been randomly selected under a regular manufacturing process. The temperature decrease time plots drawn starting 75 min after death for the eyeball, the orbit soft tissues, the rectum and muscle tissue were found to fit the single-exponential thermodynamic model originally proposed by H. Rainy in 1868. In view of the actual intersubject variability, the addition of a second exponential term to the model was demonstrated to be statistically insignificant. Therefore, the two-exponential model for death time estimation frequently recommended in the forensic medicine literature, even if theoretically substantiated for individual test cases, provides no advantage as regards the reliability of estimation in an actual case. The improvement of the precision of time of death estimation by the reconstruction of an individual curve on the basis of two dead body temperature measurements taken 1 h apart or taken continuously for a longer time (about 4 h), has also been proved incorrect. It was demonstrated that the reported increase of precision of time of death estimation due to use of a multiexponential model, with individual exponential terms to account for the cooling rate of the specific body sites separately, is artifactual. The results of this study support the use of the eyeball and/or the orbit soft tissues as temperature measuring sites at times shortly after death. A single-exponential model applied to the eyeball cooling has been shown to provide a very precise estimation of the time of death up to approximately 13 h after death. For the period thereafter, a better estimation of the time of death is obtained from temperature data collected from the muscles or the rectum.     

The variability of clinical presentation of chronic obstructive pulmonary disease in patients with hereditary alpha-1 antitrypsin deficiency

Four patients with alpha-1 antitrypsin (alpha-1 AT) deficiency are presented: one woman with severe (phenotype PiZ) and 3 men with moderate (phenotype PiMZ) deficiency of alpha-1 AT. The variability of clinical presentation of hereditary emphysema is described. In all patients tobacco smoking history, spirometric and 6-minutes walking tests as well as HRCT of the lung were performed and compared. The influence of smoking on the functional status is underlined.     

Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats

We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.     

Clinical and molecular-cytogenetic evaluation of a family with partial Jacobsen syndrome without thrombocytopenia caused by an approximately 5 Mb deletion del(11)(q24.3)

Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between approximately 7 and 20 Mb. Typical JBS features include developmental delay/mental retardation, short stature, congenital heart defects, thrombocytopenia, and characteristic dysmorphic facial features. We report on a family in which a 4-year-old girl as well as her mother and maternal uncle present with subtle features of JBS. Notably, neither thrombocytopenia nor congenital anomalies were detected in this family. Cytogenetic analyses revealed normal karyotypes. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an approximately 5 Mb deletion of the terminal part of chromosome 11q in all the three affected family members. The deletion breakpoint was mapped between 129,511,419 and 129,519,794 bp. This is the smallest deletion reported in a JBS patient. Interestingly, the FLI1 (friend leukemia virus integration 1) hematopoiesis factor gene located approximately 6.5 Mb from 11qter and usually deleted in patients with JBS, is intact. Our data support previous hypotheses that FLI1 haploinsufficiency is responsible for thrombocytopenia in patients with JBS.     

The Immunohistochemical Analysis of RCAS1, HLA‐G,and B7H4‐Positive Macrophages in Partial and Complete Hydatidiform Mole in Both Applied Therapeutic Surgery and Surgery Followed by Chemotherapy

Citation Basta P, Galazka K, Mach P, Jozwicki W, Walentowicz M, Wicherek L. The immunohistochemical analysis of RCAS1, HLA‐G, and B7H4‐positive macrophages in partial and complete hydatidiform mole in both applied therapeutic surgery and surgery followed by chemotherapy. Am J Reprod Immunol 2011; 65: 164–172 Introduction The suppressive microenvironment developing around the implantating ovum in normal pregnant women may correlate with the development in cancer patients of a suppressive microenvironment of neoplasmatic cells derived from trophoblasts, such as occurs in molar lesions. Macrophages are suitable candidates for mediating not only the balance of the maternal defensive immune responses to external antigens, but also a tolerance to tumor cells. The aim of our study has been to gain information about the expression of RCAS1, B7H4, and HLA‐G within the macrophages present in the microenvironment of the molar lesion. Methods We analyzed the immunoreactivity of such antigens as B7H4, RCAS1, and HLA‐G on the macrophages present in tissue samples derived from patients on whom curettage was performed after a diagnosis of molar pregnancy. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. Results We observed a statistically significant increase in the RCAS1‐positive macrophage infiltration within the microenvironment of the molar lesions in patients with partial hydatidiform mole in comparison with those patients who exhibited complete hydatidiform mole. There were no such differences, however, in the infiltration of HLA‐G‐ and B7H4‐positive macrophages between the two groups of patients. Additionally, we showed that RCAS1‐ and HLA‐G‐positive macrophages are more distinct in those cases of complete molar pregnancy where chemotherapy was necessary after surgical treatment while no such differences with respect to B7H4‐positive macrophages were observed. Conclusion The immune‐suppressive endometrial microenvironment represented by suppressive macrophages may have an influence on the clinical course of hydatidiform mole.