Hypoxic-ischemic injury stimulates subventricular zone proliferation and neurogenesis in the neonatal rat

Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and increases in the adult after brain injury. In this study, postnatal day 7 (P7) rats underwent right carotid artery ligation followed by 8% O2 exposure for 90 min, a lesioning protocol that resulted in ipsilateral forebrain hypoxic-ischemic (HI) injury. The effects of HI injury on SVZ cell proliferation and neurogenesis were examined 1-3 wk later by morphometric measurement of dorsolateral SVZ size; by immunoassays to detect incorporation of bromodeoxyuridine (BrdU) in proliferating cells; and by immunoassays of doublecortin, a microtubule-associated protein expressed only by immature neurons. For determining the cell phenotypes of newly generated cells, tissue sections were double labeled with antibodies to BrdU and markers of mature neurons (neuronal nuclear protein), astrocytes (glial fibrillary acidic protein), or oligodendroglia (RIP). HI injury resulted in enlargement of the ipsilateral SVZ at P14-28 and a corresponding increase in BrdU cell numbers both in the ipsilateral SVZ and striatum at P21. HI injury also stimulated SVZ neurogenesis, based on increased doublecortin immunostaining in the SVZ ipsilateral to lesioning at P14-28. However, 4 wk after HI injury, in the lesioned striatum, although BrdU/glial fibrillary acidic protein and BrdU/RIP-labeled cells were identified, no BrdU/neuronal nuclear protein double-labeled cells were found. These results suggest that although acute neonatal HI injury stimulates SVZ proliferation and neurogenesis, there is inadequate trophic support for survival of newly generated neurons. Identification of the trophic factors that enhance maturation and survival of immature neurons could provide important clues for improving recovery after neonatal brain injury.     

The role of thorax imaging in staging head and neck squamous cell carcinoma

The overall survival rate for patients with head neck squamous cell carcinoma remains disappointingly static despite improved locoregional control. This has been attributed to the development of distant metastases and second primary malignancies in these patients, a large proportion of which occur in the thorax. We retrospectively analysed the incidence of thoracic malignancies in 138 patients presenting with newly diagnosed (n = 107) or recurrent (n = 31) cancer of the head and neck over a 4-year period. All 138 patients had undergone both computerised tomography of the thorax (CT) and conventional chest radiography within one month of presenting with biopsy proven squamous cell carcinoma. Seventeen percent of these were found to have simultaneous thoracic malignancies. CT thorax was more sensitive in detecting simultaneous thoracic malignancies compared with standard chest X-ray (24/138 versus 9/138, odds ratio of 3:1 in favour of CT). All thoracic malignancies detected by chest X-ray were also detected by CT thorax. Patients presenting with recurrent tumors were significantly more likely to have simultaneous thoracic malignancies than those with newly diagnosed cancer (11/31 versus 13/107, chi2 test with Yates correction, chi2 = 4.66, p = 0.03). The primary site (laryngeal, oral or pharyngeal) or presence of nodal disease did not have an effect on the incidence of simultaneous thoracic malignancies. The presence of distant metastases and second primary malignancies has major implications in the management and prognosis of patients presenting with head and neck squamous cell carcinoma, with a large proportion of such patients succumbing to their disease within one year of diagnosis. As CT scanning of the thorax was a more effective screening investigation than standard chest X-ray in the detection of simultaneous thoracic malignancy, we recommend it for use in the staging of patients presenting with cancer of the head and neck.     

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Serum pregnancy-specific beta1-glycoprotein before embryo transfer is related to endometrial thickness and to outcome prognosis in women undergoing in-vitro fertilization treatment

We have previously observed the repeated presence of low but detectable amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein (SP1) in the serum of some women undergoing in-vitro fertilization (IVF) treatment around the time of oocyte retrieval. The occurrence of these signals seemed to be restricted to a defined group of patients which also showed a lower pregnancy success rate in a preliminary study. To test our hypothesis we have analysed 173 consecutive cycles leading to an embryo transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1 ng/ml between days embryo transfer -5 and embryo transfer (group A). Five pregnancies were obtained in this group (pregnancy rate = 9.3%), while in group B, defined by the absence of detectable SP1 before embryo transfer (119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41 pregnancies were achieved in 33 first-time non-pregnant patients undergoing further attempts during the study period. Again the pregnancy rate was higher in the first-time group B women (9/23 versus 1/10 for group A). Patients tended to remain in their groups A or B, the latter being associated with a better immediate as well as subsequent chance for pregnancy. Group A cycles had a significantly lower endometrial thickness two days before oocyte retrieval than group B (P = 0.0011). We postulate that the presence of an unknown, maternal and progesterone- or follicle stimulating hormone-independent factor in some patients could stimulate tonic ectopic SP1 synthesis and at the same time negatively influence endometrial development.      

Binge eating in Parkinson's disease: prevalence, correlates and the contribution of deep brain stimulation

Of 96 Parkinson's disease patients surveyed at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge-eating disorder. Eight (8.3%) exhibited subthreshold binge eating. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, compulsive buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse-control disorder (67% versus 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% versus 41%). More overeaters had a history of subthalamic deep brain stimulation (DBS; 44% versus 14%). History of DBS was the only independent predictor of overeating.     

Psychiatric Advance Directives and their relevance to improving psychiatric care in Asian countries

People with mental illness may be unable to provide critical input about the care they wish to receive during a psychiatric crisis because of altered mental states. It is therefore imperative that clinicians seek to understand service users' wishes for care while they are well and able to provide meaningful input into the discussion. Achieving such an end may be done by discussing and completing a psychiatric advance directive. However, very few Asian countries have legislation that supports such advance directives. The present article seeks to give physicians more information about advance psychiatric directives and the potential role they could play to improve the healthcare provided in Asia to people at risk of losing capacity due to a mental illness. The degree to which mental health legislation supports psychiatric advance directives is documented for each country of South East Asia and Eastern Asia.