Oocyte maturation arrest produced by TUBB8 mutations: impact of genetic disorders in infertility treatment

Abstract

Oocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis.     

Altered central micro-opioid receptor binding after psychological trauma.

BACKGROUND: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing. METHODS: Here we examined the micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n = 14) and without combat exposure (n = 15). Differences in micro-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions. RESULTS: Relative to healthy controls, both trauma-exposed groups had lower micro-opioid receptor BP2 in extended amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior cingulate cortex compared with both control groups. Micro-opioid receptor BP2 in combat-exposed subjects without PTSD was lower in the amygdala but higher in the orbitofrontal cortex compared with both PTSD patients and healthy controls. CONCLUSIONS: These findings differentiate the general response of the micro-opioid system to trauma from more specific changes associated with PTSD.     

Psychosocial factors associated with poor diabetes self-care management in a specialized Center in Mexico City

To examine the relationship between demographic, clinical and psychosocial variables and diabetes self-care management in Mexican type 2 diabetic patients. Cross-sectional study of 176 consecutive patients with type 2 diabetes aged 30-75 years, attending a tertiary health-care center in Mexico City. A brief medical history and previously validated questionnaires were completed. The study group consisted of 64 males/112 females, aged 55 +/- 11 years, mean diabetes duration of 12 +/- 8 years and HbA1c of 9.0 +/- 2.0%, 78.4% reported following the correct dose of diabetes pills or insulin, 58% ate the recommended food portions, and 44.3% did exercise three or more times per week. A good adherence to these three recommendations was observed in only 26.1% of the patients. These patients considered as a group were characterized by a greater knowledge about the disease (P < 0.00001), regular home blood glucose monitoring (P < 0.01), an inner perception of better diabetes control (P = 0.007), good health (P = 0.004) and better communication with their physician (P < 0.02). A poor adherence to two or the three main diabetes care recommendations was associated with a depressive state (OR 2.38, 95% CI 1.1-4.9, P < 0.01) and a history of excessive alcohol intake (OR 4.03, 95% CI 1.1-21.0, P = 0.03). Poor adherence to standard diabetes care recommendations is frequently observed in patients with type 2 diabetes attending a specialized health care center in Mexico City. Depression must be identified and treated effectively.     

Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.     

Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies.

BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications. METHODS AND RESULTS: Fifty consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). CONCLUSIONS: Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.     

Developmental regulation of annexin II (Lipocortin 2) in human brain and expression in high grade glioma.

In experiments to identify molecules that might be important in the pathogenesis of glioblastoma multiforme, the most common malignant brain tumor, we found that annexin II (Lipocortin 2, p36), a likely second messenger in several different mitogenic pathways, was highly expressed in tumor tissue of glioblastoma multiforme (9 of 9) and highly anaplastic astrocytoma (2 of 6), but not in astrocytomas of lower pathological grade (0 of 6). We also detected high levels of annexin II expression in fetal brain during the period when radial glia proliferate, although annexin II expression was not detected in normal adult brain. These data demonstrate that annexin II expression is developmentally regulated in the human central nervous system and suggest that the early progenitor radial glia share important characteristics with highly malignant glial tumors.     

Ga-67 uptake unsuppressed by leukopenia and intense antibiotic therapy.

The authors describe a patient with myelofibrosis who showed intense Ga-67 uptake in spite of being severely leukopenic and receiving large amounts of antibiotics. They conclude that false-negative results associated with leukopenia or intensive antibiotic treatment may not always be correct.     

Giant splenic metastasis due to lung adenocarcinoma

Lung cancer is the most prevalent malignancy in western countries and most of the patients present at advanced stages, but single splenic metastasis is exceptional instead. We report on a case of a seventy-three-year old male presenting with non-hemoptoic productive cough, constitutional syndrome and pain in the left lower quadrant. Physical examination and complementary radiological and hystologycal procedures revealed the presence of an adenocarcinoma of the left lung with probable splenic metastasis. The patient underwent splenectomy, which confirmed the diagnose of splenic metastasis of lung adenocarcinoma and, secondly, lung resection was performed. Topics about lung cancer metastasis are discussed.