Automatic brain segmentation in preterm infants with post‐hemorrhagic hydrocephalus using 3D Bayesian U‐Net

Post‐hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH) in very preterm infants. PHH monitoring and treatment decisions rely heavily on manual and subjective two‐dimensional measurements of the ventricles. Automatic and reliable three‐dimensional (3D) measurements of the ventricles may provide a more accurate assessment of PHH, and lead to improved monitoring and treatment decisions. To accurately and efficiently obtain these 3D measurements, automatic segmentation of the ventricles can be explored. However, this segmentation is challenging due to the large ventricular anatomical shape variability in preterm infants diagnosed with PHH. This study aims to (a) propose a Bayesian U‐Net method using 3D spatial concrete dropout for automatic brain segmentation (with uncertainty assessment) of preterm infants with PHH; and (b) compare the Bayesian method to three reference methods: DenseNet, U‐Net, and ensemble learning using DenseNets and U‐Nets. A total of 41 T₂‐weighted MRIs from 27 preterm infants were manually segmented into lateral ventricles, external CSF, white and cortical gray matter, brainstem, and cerebellum. These segmentations were used as ground truth for model evaluation. All methods were trained and evaluated using 4‐fold cross‐validation and segmentation endpoints, with additional uncertainty endpoints for the Bayesian method. In the lateral ventricles, segmentation endpoint values for the DenseNet, U‐Net, ensemble learning, and Bayesian U‐Net methods were mean Dice score = 0.814 ± 0.213, 0.944 ± 0.041, 0.942 ± 0.042, and 0.948 ± 0.034 respectively. Uncertainty endpoint values for the Bayesian U‐Net were mean recall = 0.953 ± 0.037, mean  negative predictive value = 0.998 ± 0.005, mean accuracy = 0.906 ± 0.032, and mean AUC = 0.949 ± 0.031. To conclude, the Bayesian U‐Net showed the best segmentation results across all methods and provided accurate uncertainty maps. This method may be used in clinical practice for automatic brain segmentation of preterm infants with PHH, and lead to better PHH monitoring and more informed treatment decisions.     

Contraception during perimenopause.

Perimenopause marks the transition from normal ovulation to anovulation and ultimately to permanent loss of ovarian function. Fecundity, the average monthly probability of conception, declines by half as early as the mid-forties, however women during the perimenopause still need effective contraception. Issues arising at this period such as menstrual cycle abnormalities, vasomotor instability, the need for osteoporosis and cardiovascular disease prevention, as well as the increased risk of gynecological cancer, should be taken into consideration before the initiation of a specific method of contraception. Various contraceptive options may be offered to perimenopausal women, including oral contraceptives, tubal ligation, intrauterine devices, barrier methods, hormonal injectables and implants. Recently, new methods of contraception have been introduced presenting high efficacy rates and minor side-effects, such as the monthly injectable system, the contraceptive vaginal ring and the transdermal contraceptive system. However, these new methods have to be further tested in perimenopausal women, and more definite data are required to confirm their advantages as effective contraceptive alternatives in this specific age group. The use of the various contraceptive methods during perimenopause holds special benefits and risks that should be carefully balanced, after a thorough consultation and according to each woman's contraceptive needs.     

Novel thyrotropin-releasing hormone analogs: a patent review

INTRODUCTION: The potential therapeutic applications of thyrotropin-releasing hormone (TRH) have attracted attention, based on its broad-spectrum neuropharmacological action rather than its endocrine properties. These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia. AREAS COVERED: This review summarizes the patent literature and advances in the discovery and development of novel TRH analogs over the past 20 years. It provides a comprehensive overview of the development of new TRH analogs, giving emphasis to their pharmaceutical profile. EXPERT OPINION: The use of TRH in the treatment of various CNS disorders has been proven clinically. However, TRH itself is a poor drug candidate due to its short plasma half-life (5 min), poor biopharmaceutical properties (low intestinal and CNS permeability) and endocrine side effect. Nevertheless, researchers have come up with metabolically stable, more potent and selective TRH analogs and prodrugs. Taltirelin, one of the TRH analogs, has been approved under the trade name of Ceredist(?) in Japan for the treatment of spinocerebellar degeneration. Several other TRH analogs are in various stages of preclinical or clinical development.     

Novel 4-(morpholin-4-yl)-N′-(arylidene)benzohydrazides: Synthesis, antimycobacterial activity and QSAR investigations

A series of 4-(morpholin-4-yl)-N′-(arylidene)benzohydrazides were synthesized using appropriate synthetic route. Antimycobacterial activity of the synthesized compounds (5a–5j) was carried out and percentage reduction in relative light units (RLU) was calculated using luciferase reporter phages (LRP) assay. Percentage reduction in relative light units (RLU) for isoniazid was also calculated. The test compounds showed significant antitubercular activity against Mycobacterium tuberculosis H37Rv and clinical isolates: S, H, R, and E resistant M. tuberculosis, when tested in vitro.Quantitative structure–activity relationship (QSAR) investigation with 2D-QSAR analysis was applied to find a correlation between different experimental or calculated physicochemical parameters of the compounds studied and 3D-QSAR analysis and to indicate the exact steric and electronic requirements in the ranges at various positions around pharmacophore.In general Schiff bases exhibit antimycobacterial activity and morpholine ring is important for antimicrobial activity. So we have synthesized 10 different 4-(morpholin-4-yl)-N′-(arylidene)benzohydrazides. The structures of new compounds were characterized by TLC, FTIR, ¹H NMR, mass spectral data and elemental analysis.Amongst the compounds tested 5d and 5c were found to be the most potent, while 5i, 5e, and 5j were found to have an average activity against M. tuberculosis H37Rv and 5a, 5f, 5h, 5g, and 5b were found to have a greater activity against clinical isolates: S, H, R, and E resistant M. tuberculosis as compared to M. tuberculosis H37Rv.     

Solitary subcutaneous metastatic deposit from hepatocellular carcinoma

Hepatocellular carcinoma is the most common primary tumour of the liver. Metastasis is frequent in these aggressive tumours and is commonly to the lungs, regional lymph nodes, or bone. Metastasis as a discrete subcutaneous nodule has not been described before. We report a case of hepatocellular carcinoma with a solitary subcutaneous metastatic deposit identified 18 months after the initial hepatic surgery.     

Pattern of expression of genes linked to epigenetic silencing in human breast cancer

Epigenetic mechanisms such as DNA methylation are now recognized to play an important role in neoplasia. The aim of this study is to relate the pattern of expression of multiple cancer genes known to undergo epigenetic inactivation by promoter hypermethylation in breast cancer with histologic and outcome data. We used immunohistochemistry to study expression of the tumor suppressor gene p16, estrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR), and the DNA repair gene MGMT (O6 -methylguanine-DNA methyltransferase) in a panel of 200 breast cancers. Methylation-specific polymerase chain reaction was used to confirm MGMT promoter methylation. Loss of expression of MGMT, ERalpha, ERbeta, PR, and p16 was observed in 19%, 24%, 13%, 40%, and 50% of cases, respectively. A significant correlation was seen between grade III tumor and loss of expression of ERalpha, ERbeta, PR (all P < .0001), and MGMT (P = .04), whereas loss of expression of p16 was associated with grades I and II tumors (P < .001). Cases that expressed 3 or less of the 5 proteins studied had significantly reduced survival (P = .0016). Methylation-specific polymerase chain reaction in a subset of 20 cancers showed DNA methylation associated with the loss of MGMT expression (P < .001). In conclusion, there is silencing of several key genes in breast cancer affecting molecular pathways involved in cell immortalization, DNA repair, and hormonal regulation, and this correlates significantly with risk of cancer-specific death. This expression profile could be linked to epigenetic events, and if so, these pathways have potential as targets for therapeutic strategies based on reversal of epigenetic silencing.     

Acute encephalopathy with a lesion of the splenium of the corpus callosum--a report of two cases

We report two cases of encephalopathy following a short febrile illness. Case one was a five year old child whose magnetic resonance imaging (MRI) of the brain showed a reversible discrete lesion in the splenium of the corpus callosum (SCC) and a ten year old boy who had extensive hyperintensity of the SCC. As these children have presented while there was an outbreak of influenza in our locality and since the second child tested positive for H1N1 antigen on PCR test, we feel that as previous authors have pointed out, these cases are cases of possible influenza encephalopathy. This awareness needs to be disseminated as this specific MRI finding should prompt one to test for H1N1 antigen and offer specific antiviral agent. Case one showed signs that support the existence of a splenial syndrome.