Incidence of Chromosomal Abnormalities from a Morphologically Normal Cohort of Embryos in Poor-Prognosis Patients

Purpose: Preimplantation genetic diagnosis of aneuploidy was performed on the embryos yielded by 70 poor-prognosis patients, with the aim of transferring those with a normal chromosomal complement, thus possibly increasing the chances of pregnancy. Methods: Multicolor fluorescence in situ hybridization (FISH) was applied for the simultaneous detection of chromosomes X, Y, 13, 16, 18, and 21. Inclusion criteria were (1) a maternal age of 36 years or older (n = 33), (2) three or more previous in vitro fertilization cycles (n = 20), and (3) an altered karyotype (n = 17). Results: A total of 412 embryos underwent FISH, resulting in 234 (57%) that were chromosomally abnormal. Euploid embryos were available for transfer in 59 patients, generating 19 pregnancies (32%), with an implantation rate of 19.9%. Conclusions: High rates of chromosomally abnormal embryos in poor-prognosis patients can determine repeated in vitro fertilization failures when embryo selection is performed on the basis of morphological criteria alone. Hence, the FISH analysis could represent the prevailing approach for the identification of embryos possessing full potential for developing to term.     

Tinnitus impairs cognitive efficiency

Many people who complain of tinnitus say that the noises impair their mental concentration. This complaint was investigated by self-report (primarily the Cognitive Failures Questionnaire) and by means of five cognitive tasks, four presented via laptop computer and one given manually. The tasks measured performance under single and dual-task conditions and included tests of sustained attention, reaction time, verbal fluency and immediate and delayed memory. Two groups of outpatients attending audiological clinics (tinnitus, n?=?43; hearing impairment, n?=?17) were compared with non-clinical volunteers (n?=?32). The results replicated earlier findings that tinnitus outpatients report significantly more everyday cognitive failures than do controls. The tinnitus group responded significantly more slowly than the two control groups on the variable fore-period reaction time task under dual-task conditions. In general, comparisons between the groups on other tasks showed equivalent performance, but both clinical groups performed more poorly than non-clinical controls on verbal fluency. We conclude that cognitive inefficiency in tinnitus participants is related to the control of attentional processes, consistent with our earlier theoretical speculation about the nature of tinnitus complaint and with published findings on the effects of chronic pain on cognitive processes.     

Fetal rejection: infertility and immunity

Defective reaction toward fetal alloantigens could result in both recurrent spontaneous abortions (RSAs) and recurrent early pregnancy failures (REPFs), the latter existing in couples with unexplained infertility and multiple failures of implantation after in vitro fertilization embryo transfer. Immunological mechanisms leading to RSA and REPF seem to be different, although both syndromes probably have a genetic background that has not been identified so far. Despite the fact that antiphospholipid syndrome is a well-established cause of repeated pregnancy loss, the role of different autoantibodies existing in RSA and REPF patients needs to be elucidated. Immunotherapy is believed to correct the detrimental immune reactions; however, its real effectiveness and safety for the treatment of distinct forms of pregnancy loss need to be reconsidered.     

Tympanometry and Fistula Test

The ‘fistula test’ is performed when an abnormal opening between the vestibule and the middle ear cavity is suspected. The fistula is usually seen after stapedectomy, but may also occur after trauma to a normal ear when the round window membrane may rupture. Tympanometry with an electronystagmographic (ENG) tracing may show a positive result after stapedectomy in the absence of a fistula, and there may conversely be a normal ENG tracing after tympanometry when there is in fact a perilymph fistula. The authors explain the reasons for this paradoxical response. In no way does it detract from the value of the test, which only needs to be interpreted correctly.     

Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential,inconsistent, and difficult

Before amyloid formation, peptides cleaved from the amyloid precursor protein (APP) exist as soluble oligomers. These are extremely neurotoxic. Their concentration is strongly correlated with synaptic impairment in animals and parallel cognitive decline in animals and humans. Clinical trials have largely been aimed at removing insoluble beta amyloid in senile plaques and have not reduced soluble load. Even treatment that should remove soluble oligomers has not consistently reduced the load. Failure to significantly improve cognition has frequently been attributed to failure of the amyloid hypothesis or to irreversible alteration in the brain. Instead, trial failures may be because of failure to significantly reduce load of toxic Aβ oligomers. Moreover, targeting only synthesis of Aβ peptides, only the oligomers themselves, or only the final insoluble amyloid may fail to significantly reduce soluble load because of the interrelationship between these 3 points in the amyloid cascade. Thus, treatments may fail unless trials target simultaneously all 3 points in the equation–"triple therapy". Cerebrospinal fluid analysis and other monitoring tools may in the future provide reliable measurement of soluble load. But currently, only analysis of autopsied brains can provide this data and thus enable proper evaluation and explanation of the outcome of clinical trials. These data are essential before attributing trial failures to the advanced nature of the disease or asserting that failures prove that the theory linking Alzheimer's disease to products of amyloid precursor protein is incorrect.