Diagnostic Tests in the Prediction of Neonatal Outcome in Early Placental Fetal Growth Restriction.

Background and Objectives: Monitoring pregnancies with fetal growth restriction (FGR) presents a challenge, especially concerning the time of delivery in cases of early preterm pregnancies below 32 weeks. The aim of our study was to compare different diagnostic parameters in growth-restricted preterm neonates with and without morbidity/mortality and to determine sensitivity and specificity of diagnostic parameters for monitoring preterm pregnancies with early preterm fetal growth restriction below 32 weeks. Materials and Methods: Our clinical study evaluated 120 cases of early preterm deliveries, with gestational age ≤ 32 + 0 weeks, with prenatally diagnosed placental FGR. All the patients were divided into three groups of 40 cases each based on neonatal condition,: I-Neonates with morbidity/mortality (NMM); II-Neonates without morbidity with acidosis/asphyxia (NAA); III-Neonates without neonatal morbidity/acidosis/asphyxia (NWMAA). Results: Amniotic fluid index (AFI) was lower in NMM, while NWMAA had higher biophysical profile scores (BPS). UA PI was lower in NWMAA. NWMAA had higher MCA PI and CPR and fewer cases with CPR <5th percentile. NMM had higher DV PI, and more often had ductus venosus (DV) PI > 95th‱ or absent/reversed A wave, and pulsatile blood flow in umbilical vein (UV). The incidence of pathological fetal heart rate monitoring (FHRM) was higher in NMM and NAA, although the difference was not statistically significant. ROC calculated by defining a bad outcome as NMM and a good outcome as NAA and NWMAA showed the best sensitivity in DV PIi. ROC calculated by defined bad outcome in NMM and NAA and good outcome in NWMAA showed the best sensitivity in MCA PI. Conclusions: In early fetal growth restriction normal cerebral blood flow strongly predicts good outcomes, while pathological venous blood flow is associated with bad outcomes. In fetal growth restriction before 32 weeks, individualized expectant management remains the best option for the optimal timing of delivery.

Behavioural Classification of Cattle Using Neck-Mounted Accelerometer-Equipped Collars.

Monitoring and classification of dairy cattle behaviours is essential for optimising milk yields. Early detection of illness, days before the critical conditions occur, together with automatic detection of the onset of oestrus cycles is crucial for obviating prolonged cattle treatments and improving the pregnancy rates. Accelerometer-based sensor systems are becoming increasingly popular, as they are automatically providing information about key cattle behaviours such as the level of restlessness and the time spent ruminating and eating, proxy measurements that indicate the onset of heat events and overall welfare, at an individual animal level. This paper reports on an approach to the development of algorithms that classify key cattle states based on a systematic dimensionality reduction process through two feature selection techniques. These are based on Mutual Information and Backward Feature Elimination and applied on knowledge-specific and generic time-series extracted from raw accelerometer data. The extracted features are then used to train classification models based on a Hidden Markov Model, Linear Discriminant Analysis and Partial Least Squares Discriminant Analysis. The proposed feature engineering methodology permits model deployment within the computing and memory restrictions imposed by operational settings. The models were based on measurement data from 18 steers, each animal equipped with an accelerometer-based neck-mounted collar and muzzle-mounted halter, the latter providing the truthing data. A total of 42 time-series features were initially extracted and the trade-off between model performance, computational complexity and memory footprint was explored. Results show that the classification model that best balances performance and computation complexity is based on Linear Discriminant Analysis using features selected through Backward Feature Elimination. The final model requires 1.83 ± 1.00 ms to perform feature extraction with 0.05 ± 0.01 ms for inference with an overall balanced accuracy of 0.83.

Classification of Cattle Behaviours Using Neck-Mounted Accelerometer-Equipped Collars and Convolutional Neural Networks.

Monitoring cattle behaviour is core to the early detection of health and welfare issues and to optimise the fertility of large herds. Accelerometer-based sensor systems that provide activity profiles are now used extensively on commercial farms and have evolved to identify behaviours such as the time spent ruminating and eating at an individual animal level. Acquiring this information at scale is central to informing on-farm management decisions. The paper presents the development of a Convolutional Neural Network (CNN) that classifies cattle behavioural states ('rumination', 'eating' and 'other') using data generated from neck-mounted accelerometer collars. During three farm trials in the United Kingdom (Easter Howgate Farm, Edinburgh, UK), 18 steers were monitored to provide raw acceleration measurements, with ground truth data provided by muzzle-mounted pressure sensor halters. A range of neural network architectures are explored and rigorous hyper-parameter searches are performed to optimise the network. The computational complexity and memory footprint of CNN models are not readily compatible with deployment on low-power processors which are both memory and energy constrained. Thus, progressive reductions of the CNN were executed with minimal loss of performance in order to address the practical implementation challenges, defining the trade-off between model performance versus computation complexity and memory footprint to permit deployment on micro-controller architectures. The proposed methodology achieves a compression of 14.30 compared to the unpruned architecture but is nevertheless able to accurately classify cattle behaviours with an overall F1 score of 0.82 for both FP32 and FP16 precision while achieving a reasonable battery lifetime in excess of 5.7 years.

T cell deficiencies as a common risk factor for drug associated progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a disease of the central nervous system caused by neuropathogenic prototypes of ubiquitous community-acquired JC virus (JCV). The disease became of particular concern following its association with certain therapies that modulate immune system function without heavy immunosuppression. Due to lack of prophylactic/treatment options and poor outcomes, which often include severe disability or death, PML is a considerable concern for development of new drugs that interfere with immune system functions. In this review of clinical and research findings, we discuss the evidence that deficiencies in CD4+ T helper cells, cytotoxic CD8+ T cells, and interferon gamma are of crucial importance for development of PML under a variety of circumstances, including those associated with use of various drugs, regardless of differences in their mechanisms of action. These deficiencies apparently enable transformation of the harmless JCV archetype into neuropathogenic prototypes, but the site(s), and the mechanisms, of this transformation are yet to be elucidated. Here we discuss the evidence for brain as one of the sites of this transformation, and propose a model of PML pathogenesis that emphasizes the central role of T cell deficiencies in the two life cycles of the JCV, one non-pathogenic and one neuropathogenic. Finally, we conclude that the development of clinical grade T cell functional tests and more consistent use of already available laboratory tests for T cell subset analysis would greatly aid the effort to more accurately predict and assess the magnitude of PML risk for concerned therapeutic interventions.

Progressive multifocal leukoencephalopathy: current treatment options and future perspectives.

Progressive multifocal leukoencephalopathy (PML) is a rare but debilitating and frequently fatal viral disease of the central nervous system, primarily affecting individuals with chronically and severely suppressed immune systems. The disease was relatively obscure until the outbreak of HIV/AIDS, when it presented as one of the more frequent opportunistic infections in this immune deficiency syndrome. It attracted additional attention from the medical and scientific community following the discovery of significant PML risk associated with natalizumab, a monoclonal antibody used for treatment of relapsing-remitting multiple sclerosis. This was followed by association of PML with other immunosuppressive or immunomodulating drugs. PML is currently untreatable disease with poor outcomes, so it is a significant concern when developing new immunotherapies. Current prophylaxis and treatment of PML are focused on immune reconstitution, restoration of immune responses to JC virus infection, and eventual suppression of immune reconstitution inflammatory syndrome. This approach was successful in reducing the incidence of PML and improved survival of PML patients with HIV infection. However, the outcome for the majority of PML patients, regardless of their medical history, is still relatively poor. There is a high unmet need for both prophylaxis and treatment of PML. The aim of this review is to discuss potential drug candidates for prophylaxis and treatment of PML with a critical review of previously conducted and completed PML treatment studies as well as to provide perspectives for future therapies.

[Woman with surgical reconstruction of anal atresia who realized pregnancy with in vitro fertilisation].

INTRODUCTION: Anal atresia is a congenital anomaly, very life-threatening and urgent. Surgical treatment of this anomaly consists of colostomy first, and then of anal reconstruction. CASE REPORT: We presented a 31-year old female with the surgery treatment of anal atresia in the early childhood. In the reproductive period, due to tubal infertily, the patient was included in the program of in vitro fertilization (IVF), in the Clinic for Gynecology and Obstetrics "Narodni front", Belgrade. Within this program a long protocol of ovarian stimulation was performed. Ultrasonographic and color Doppler monitoring of the patient was applied by the use of an ultrasonographic apparatus type Siemens Acuson X 150, while any hormonal examinations were performed by an Architect Abbott unit. During the IVF program, the growth of follicules was controlled by the use of ultrasonography, microcirculation of the ovaries and the uterus was marked by a power-pulsating color Doppler, and hormonal examination was performed starting from the day of stimulation up to the day of injecting Pregnyl. The patient was administered Suprefact (buserelin) sc from the 21st day of the menstrual cycle, as well as from the 3rd day of the cycle, for totally 11 days. The patient was given 29 ampoules of Gonal F (recombinant human FSH) 75 IJ im and 15 ampoules of Menopur (menotrophin) im. Due to a modified pelvic anatomy, the left ovary aspiration was disabled, while the right ovary aspired seven oocytes successfully. Three embryos were inserted in the uterus. The delivery was performed by cesarean section. CONCLUSION: In the reported patient with a modified pelvic anatomy due to four corrective surgeries of anal atresia, and tubal infertility in the reproductive period, the method of choice for the realization of pregnancy was the IVF procedure. The realized pregnancy and the delivery could be considered highly successful in regard to possible risks.

Xenotransplantation of purified pre-natal porcine beta cells in mice normalizes diabetes when a short anti-CD4-CD8 antibody treatment is combined with transient insulin injections.

BACKGROUND: Pre-natal porcine endocrine islet cell grafts were recently shown to contain immature beta cells with a marked potential for growth and differentiation following transplantation, and hence for a progressive and long-term correction of diabetes in immune-incompetent mice. The present study investigates whether these grafts are also capable of correcting hyperglycemia in immune-competent mice receiving a short treatment with anti-CD4-CD8 antibodies. METHODS: Pure endocrine islet cell grafts with 0.5 to 1.0 million beta cells were prepared from pre-natal pigs and transplanted under the kidney capsule of alloxan-diabetic CBA/Ca mice. Survival, growth and function of implanted beta cells were followed by measuring plasma porcine C-peptide and glucose, and graft insulin content at start and at post-transplant (PT) week 35. The effect was studied of a 5-day treatment with non-depleting anti-CD4 YTS177 and depleting anti-CD8 YTS169 antibody, either without or with transient insulin injections. RESULTS: Without antibody treatment, all graft recipients remained porcine C-peptide negative and died. Antibody treatment decreased CD4-expression and percentage CD8 cells for 10 and 18 weeks respectively. It resulted in a 30 week-survival of nine out of 14 graft recipients; all nine had progressively become C-peptide positive but only one proceeded to normoglycemia. When antibody treatment was combined with transient insulin injections, 11 out of 14 graft recipients survived long-term, eight became C-peptide positive and six were normoglycemic at PT week 30. In both groups, surviving recipients exhibited a graft insulin content that was 6- to 9-fold higher than at implantation. CONCLUSIONS: Pre-natal porcine beta cells grow and differentiate when transplanted in diabetic immune-competent mice that have been transiently immune suppressed with anti-CD4 and anti-CD8 monoclonal antibodies. They develop metabolic control when recipients are also transiently treated with insulin injections.

[Significance of transvaginal Doppler ultrasonography for detection of malignant gestational trophoblastic disease]. / Znacaj transvaginalne Doppler ultrasonografije u deteckciji maligne gestacijske trofoblastne bolesti.

Transvaginal Doppler ultrasonography has an important role in detecting and confirming the gestational trophoblastic disease (GTD). It can also be helpful in early detection of the malignant cases of GTD such as the invasion and protrusion of trophoblastic tissue into the uterine wall. Ultrasonographic picture of the malignant GTD is also specific for the presence of prominent zones of vasculavization in the peritrophoblastic tissue, as well as in the uterine tissue in which malignant GTD is developed. Resistance Index (RI) values were measured at the level of blood vessels of peritrophoblastic tissue and of suspected zones in the uterine tissue to detect neovascularization, which followed the malignant process. Theca luteal cysts were often detected by Transvaginal Doppler ultrasonography.