Prenatal Diagnosis and Outcome of Tracheal Agenesis as Part of Congenital High Airway Obstruction Syndrome. Case Presentation and Literature Review.

Tracheal atresia is an extremely rare condition whereby a partial or total obstruction of the trachea is seen. It is almost always lethal, with just a handful of cases that ended with a good outcome. In this study we report on a 15-week male fetus, diagnosed with hyperechogenic lungs, midline heart position and inverted diaphragm. Sonographic findings suggest congenital High Airway Obstruction Syndrome (CHAOS) An ultrasound scan and fetal MRI were not able to point out the exact obstruction level. In spite of extensive counselling, the parents opted to carry on with the pregnancy. Fetal demise was noted on a scan at 19 weeks gestation. After the elective termination of pregnancy, a post-mortem examination showed partial tracheal atresia with no other anomalies. Despite technological progress in CHAOS syndrome, a precise diagnosis and accurate prognosis remain elusive.

Fatal Association of Mirror and Eisenmenger Syndrome during the COVID-19 Pandemic.

Mirror syndrome (MS) or Ballantyne's syndrome is a rare maternal condition that can be life-threatening for both mother and fetus. The condition is characterized by maternal signs and symptoms similar to those seen in preeclampsia in the setting of fetal hydrops. Despite recent advances in the field of maternal-fetal medicine, the etiopathogenesis of MS remains elusive. For patients and doctors, the COVID-19 pandemic has become an extra hurdle to overcome. The following case illustrates how patients' non-compliance associated with mirror syndrome and SARS-CoV-2 infection led to the tragic end of a 19-year-old patient. Therefore, knowledge of the signs and symptoms of mirror syndrome should always be part of the armamentarium of every obstetrician.

An Immunohistochemical Study of Gastric Mucosa and Critical Review Indicate that the Subepithelial Telocytes are Prelymphatic Endothelial Cells.

There are only a few studies regarding gut subepithelial telocytes (TCs). The telopodes, namely peculiar TCs' prolongations described on two-dimensional cuts, are not enough to differentiate this specific cell type. Subepithelial TCs were associated with the intestinal stem niche but a proper differential diagnosis with lymphatic endothelial cells (LECs) was not performed. In this study, we will critically review studies suggesting that distinctive TCs could be positioned within the lamina propria. Additionally, we performed an immunohistochemical study of human gastric mucosa to test the expression of D2-40, the lymphatic marker, as well as that of CD31, CD34, CD44, CD117/c-kit, α-smooth muscle actin (α-SMA) and vimentin in the gastric subepithelial niche. The results support the poorly investigated anatomy of intramural gastric lymphatics, with circumferential collectors located on both sides of the muscularis mucosae (mucosal and then submucosal) and myenteric collectors in the muscularis propria. We also found superficial epithelial prelymphatic channels bordered by D2-40+ but CD31-TC-like cells. Deep epithelial lymphatic collectors drain in collectors within the lamina propria. Blood endothelial cells expressed CD31, CD34, CD44, and vimentin. Therefore, the positive diagnosis of TC for subepithelial CD34+ cells should be regarded with caution, as they could also be artefacts, resulting from the two-dimensional examination of three dimensional structures, or as LECs. Lymphatic markers should be routinely used to discriminate TCs from LECs.

Interspike Intervals Reveal Functionally Distinct Cell Populations in the Medial Entorhinal Cortex.

The superficial layers of the medial entorhinal cortex (MEC) contain spatially selective neurons that are crucial for spatial navigation and memory. These highly specialized neurons include grid cells, border cells, head-direction cells, and irregular spatially selective cells. In addition, MEC neurons display a large variability in their spike patterns at a millisecond time scale. In this study, we analyzed spike trains of neurons in the MEC superficial layers of mice and found that these neurons can be classified into two groups based on their propensity to fire spike doublets at 125-250 Hz. The two groups, labeled "bursty" and "non-bursty" neurons, differed in their spike waveforms and interspike interval adaptation but displayed a similar mean firing rate. Grid cell spatial periodicity was more commonly observed in bursty than in non-bursty neurons. In contrast, most neurons with head-direction selectivity or those that fired at the border of the environment were non-bursty neurons. During theta oscillations, both bursty and non-bursty neurons fired preferentially near the end of the descending phase of the cycle, but the spikes of bursty neurons occurred at an earlier phase than those of non-bursty neurons. Finally, analysis of spike-time crosscorrelations between simultaneously recorded neurons suggested that the two cell classes are differentially coupled to fast-spiking interneurons: bursty neurons were twice as likely to have excitatory interactions with putative interneurons as non-bursty neurons. These results demonstrate that bursty and non-bursty neurons are differentially integrated in the MEC network and preferentially encode distinct spatial signals. SIGNIFICANCE STATEMENT: We report that neurons in the superficial layers of the medial entorhinal cortex can be classified based on their tendency to fire bursts of action potentials at 125-250 Hz. The relevance of this classification is demonstrated by the types of spatial information preferentially encoded by bursty and non-bursty neurons. Grid-like spatial periodicity is more commonly observed in bursty neurons, whereas most cells with head-direction selectivity or those that are firing at the border of the environment are non-bursty neurons. This work indicates that the spatial firing patterns of neurons in the medial entorhinal cortex can be predicted by electrophysiological features reflecting the synaptic inputs and/or integrating properties of the neurons.

Impaired path integration and grid cell spatial periodicity in mice lacking GluA1-containing AMPA receptors.

The hippocampus and the parahippocampal region have been proposed to contribute to path integration. Mice lacking GluA1-containing AMPA receptors (GluA1(-/-) mice) were previously shown to exhibit impaired hippocampal place cell selectivity. Here we investigated whether path integration performance and the activity of grid cells of the medial entorhinal cortex (MEC) are affected in these mice. We first tested GluA1(-/-) mice on a standard food-carrying homing task and found that they were impaired in processing idiothetic cues. To corroborate these findings, we developed an L-maze task that is less complex and is performed entirely in darkness, thereby reducing numerous confounding variables when testing path integration. Also in this task, the performance of GluA1(-/-) mice was impaired. Next, we performed in vivo recordings in the MEC of GluA1(-/-) mice. MEC neurons exhibited altered grid cell spatial periodicity and reduced spatial selectivity, whereas head direction tuning and speed modulation were not affected. The firing associations between pairs of neurons in GluA1(-/-) mice were stable, both in time and space, indicating that attractor states were still present despite the lack of grid periodicity. Together, these results support the hypothesis that spatial representations in the hippocampal-entorhinal network contribute to path integration.

Conservative Management With a Multimodal Approach of a 12-Week Cervical Ectopic Pregnancy With Fetal Megacystis.

Cervical ectopic pregnancy is the rarest kind of ectopic pregnancy, and it is known as the implantation of an embryo into the cervical mucosa. It is commonly associated with complications such as hemorrhage from the cervix and can lead to severe consequences if it is not treated early. For this reason, the treatment for a cervical pregnancy often requires an abdominal hysterectomy. To avoid such radical management, several conservative methods of termination have been used. In this paper, we report a complex management of one of our ectopic cervical cases, which includes embolization of the uterine arteries, treatment with methotrexate and mifepristone, evacuation of the pregnancy followed by local hemostatic sutures and application of a balloon in the cervix. The post-operative period was uneventful. After a three-day postoperative stay, the patient was discharged. The management options employed in the presented case achieved the goal of preserving fertility for our patient. There are no specific guidelines for the treatment of cervical pregnancies in advanced gestational age.

Fibular hemimelia.

Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and absent rays. A literature review showed only a handful of cases of prenatal diagnosis of fibular hemimelia. It is a rare disorder that might be isolated or associated with visceral anomalies.

Monochorionic Diamniotic Twins with Bordering Cord Insertions: Images and Outcome.

Twin pregnancy contributes to perinatal mortality, particularly monochorionic diamniotic twin pregnancy. Placental abnormalities are much more common in twin pregnancies than in singletons. In MCDA pregnancy, vascular anastomoses are always present and are accountable for severe complications such as Twin-to-Twin transfusion syndrome (TTTS). In TTTS, umbilical cords are usually inserted at a distance from each other. We present a rare type of MCDA pregnancy, TTTS gr 1 case with bordering umbilical cord insertions.

Pituitary adenoma apoplexy in pregnancy: Case report and literature review.

Gestational pituitary apoplexy is an extremely rare condition. It is characterised by an unexpected headache, vomiting, nausea, and visual disturbances. Pituitary apoplexy in pregnancy and postpartum is a challenging diagnosis with symptoms overlapping multiple conditions. There is a limited number of articles presenting cases or case series of gestational pituitary apoplexy. This is a potentially life-threatening emergency which requires a high index of suspicion for its diagnosis. This article presents a case of postpartum pituitary apoplexy and outlines the current stage of clinical, imagistic diagnosis and management options. A 26-year-old primipara was submitted to a Caesarean section, with no perioperative incidents. Forty-eight hours later she reported the apparition of frontal and temporal throbbing headaches, nausea, photophobia, and she was diagnosed with a pituitary tumor measuring 33x10.5x15.5 mm. Although initially conservative treatment was proposed, the clinical outcome was not favourable, thus the patient was submitted to endoscopic transsphenoidal resection. The histopathological studies demonstrated the presence of a pituitary macroadenoma. At the 2-year follow-up, the patient is free of disease. Although it represents an extremely rare condition, gestational pituitary apoplexy should be suspected whenever headache and neurological disorders such as nausea and photophobia are reported during the postpartum period.

First-trimester screening-biomarkers and cell-free DNA.

BACKGROUND: The introduction of cell-free DNA into clinical practice has changed the screening approach. Healthcare professionals and future parents tend to overestimate NIPT (noninvasive prenatal testing) capabilities despite its relatively high cost and limited information. OBJECTIVE: In this review, our aim was to survey how various countries have introduced contingent screening models and to discuss the advantages and disadvantages of the combined screening test and the use of NIPT. DATA SOURCE: The Web of Science, PubMed database and institutional websites were searched for information regarding screening approaches and the implementation in different countries. RESULTS: There are nine countries and regions that have already approved contingent screening test, while others (e.g. Australia) are discussing the implementation of contingent screening versus universal use of NIPT. There are several recent meta-analyses debating whether to use NIPT for universal screening for trisomies and other fetal conditions. CONCLUSIONS: NIPT is a reasonable option as an advanced screening test for trisomy 21, 18 and 13 only. Introducing screening by NIPT instead of a first-trimester screening will cause the loss of other valuable information including accurate dating of pregnancy, diagnosing major structural fetal abnormalities and multiple pregnancies at an early gestational age. Additionally, the opportunity to screen for early preeclampsia will be lost. Currently, the price for NIPT is still high adding extra strain on publicly funded health systems.

Tuberculosis in pregnancy.

Tuberculosis (TB) in pregnancy is not only a matter of the past; it is also a current problem. These days, TB appears through mass migration and tourism in countries where it was believed that this condition is eradicated. Adequate knowledge about the medical history of patients, risk factors, diagnosis and treatment of tuberculosis should be part of the armamentarium of each physician involved in clinical practice. TB is mainly found in urban and socially deprived areas. Due to the length of the treatment, there is an increased risk of drug resistance in partially treated patients. Strong knowledge about the history, risk factors, diagnosis and treatment of TB should be part of the armamentarium of each physician. Many practitioners are reluctant to request a chest X-ray in pregnancy due to the fear of harming the fetus. Bypassing a diagnosis can have a devastating effect on the mother and fetus, as well as their family and medical staff. This article discusses the matters of diagnosis and treatment of asymptomatic infection and active TB in pregnancy.

Glycogen-rich clear cell carcinoma of the breast with solid papillary pattern: Two cases with heterogeneous clinicopathological features.

Invasive breast cancer is a heterogeneous disease, both in its histopathological classification and clinical course. Glycogen-rich clear cell carcinoma of the breast is an extremely rare subtype of invasive breast carcinoma, accounting for up to 3% of all breast carcinomas. The tumor is composed of polygonal cells with abundant clear cytoplasm containing glycogen and has a very controversial prognosis. Solid papillary pattern is an uncommon morphological variant of breast carcinoma which is associated with indolent behavior in the absence of an invasive component. To date, there are only three cases of glycogen-rich clear cell carcinoma with solid papillary pattern reported in the English literature. In this article, we present two cases of glycogen-rich clear cell carcinoma of the breast, encountered in our daily clinical practice over a period of 5 years (2015-2020) and perform a brief review of currently published literature. Unlike most cases of glycogen-rich clear cell carcinoma documented to date, follow-up of our case featuring solid papillary pattern revealed extremely favorable clinical outcome, suggesting a better prognosis for tumors with this morphology.

Suppression of Parvalbumin Interneuron Activity in the Prefrontal Cortex Recapitulates Features of Impaired Excitatory/Inhibitory Balance and Sensory Processing in Schizophrenia.

Accumulating evidence supports parvalbumin expressing inhibitory interneuron (PV IN) dysfunction in the prefrontal cortex as a cause for cognitive impairment associated with schizophrenia (CIAS). PV IN decreased activity is suggested to be the culprit for many of the EEG deficits measured in patients, which correlate with deficits in working memory (WM), cognitive flexibility and attention. In the last few decades, CIAS has been recognized as a heavy burden on the quality of life of patients with schizophrenia, but little progress has been made in finding new treatment options. An important limiting factor in this process is the lack of adequate preclinical models and an incomplete understanding of the circuits engaged in cognition. In this study, we back-translated an auditory stimulation protocol regularly used in human EEG studies into mice and combined it with optogenetics to investigate the role of prefrontal cortex PV INs in excitatory/inhibitory balance and cortical processing. We also assessed spatial WM and reversal learning (RL) during inhibition of prefrontal cortex PV INs. We found significant impairments in trial-to-trial reliability, increased basal network activity and increased oscillation power at 20-60 Hz, and a decreased signal-to-noise ratio, but no significant impairments in behavior. These changes reflect some but not all neurophysiological deficits seen in patients with schizophrenia, suggesting that other neuronal populations and possibly brain regions are involved as well. Our work supports and expands previous findings and highlights the versatility of an approach that combines innovative technologies with back-translated tools used in humans.

MicroRNA Involvement in Signaling Pathways During Viral Infection.

The study of miRNAs started in 1993, when Lee et al. observed their involvement in the downregulation of a crucial protein known as LIN-14 in the nematode Caenorhabditis elegans. Since then, great progress has been made regarding research on microRNAs, which are now known to be involved in the regulation of various physiological and pathological processes in both animals and humans. One such example is represented by their interaction with various signaling pathways during viral infections. It has been observed that these pathogens can induce the up-/downregulation of various host miRNAs in order to elude the host's immune system. In contrast, some miRNAs studied could have an antiviral effect, enabling the defense mechanisms to fight the infection or, at the very least, they could induce the pathogen to enter a latent state. At the same time, some viruses encode their own miRNAs, which could further modulate the host's signaling pathways, thus favoring the survival and replication of the virus. The goal of this extensive literature review was to present how miRNAs are involved in the regulation of various signaling pathways in some of the most important and well-studied human viral infections. Further on, knowing which miRNAs are involved in various viral infections and what role they play could aid in the development of antiviral therapeutic agents for certain diseases that do not have a definitive cure in the present. The clinical applications of miRNAs are extremely important, as miRNAs targeted inhibition may have substantial therapeutic impact. Inhibition of miRNAs can be achieved through many different methods, but chemically modified antisense oligonucleotides have shown the most prominent effects. Though scientists are far from completely understanding all the molecular mechanisms behind the complex cross-talks between miRNA pathways and viral infections, the general knowledge is increasing on the different roles played by miRNAs during viral infections.

Non-Invasive Prenatal Testing beyond Trisomies.

The last decade has seen incredible advances in the genetic era, in next-generation sequencing of cell-free DNA in the maternal plasma, detecting abnormal fetal chromosomes. Non-invasive prenatal testing (NIPT) has showed increased sensitivity and specificity for Down syndrome superior to any other screening test. Technical advances have made possible the detection of other conditions which does not necessarily mean clinical benefit for the patient. Private laboratories have added multiple conditions in the panel of NIPT, but some of these abnormalities are so rare, that their prevalence is not even clear. Data regarding clinical performance of extended NIPT is lacking. Implementation of such a test has to be carefully weighed, and not only the benefits but also the harm should be taken into account.

The Dual Blockade in the Neoadjuvant Setting of HER-2 Positive Early-Stage Breast Cancer.

Patients with positive Her-2/neu breast cancer and a high risk of recurrence are known to benefit from the addition of the dual blockade of Her-2/neu with Trastuzumab and Pertuzumab to the neoadjuvant chemotherapy, a combination which has been demonstrated to give a higher rate of a complete pathologic response in the breast and in the axilla. The purpose of this review is to outline the efficacy of the dual blockade with Trastuzumab and Pertuzumab in the neoadjuvant treatment of high-risk Her-2 positive breast cancer. Electronic databases (Pubmed, Medline, and Cochrane Database of Systematic Reviews) were searched for English- and German-language studies, which were published in the last ten years. The search has been focused on neoadjuvant clinical trials as well as on the data presented in the abstracts published at the San Antonio Breast Cancer Symposium as well as at the annual meeting of the American Society of Clinical Oncology. The results reported in the published clinical trials demonstrated a higher pathologic complete response rate in breast and lymph nodes after using targeted therapy with two anti-Her-2/neu agents - Trastuzumab and Pertuzumab in combination with neoadjuvant chemotherapy for early-stage Her-2/neu positive breast cancers. The pathologic complete response rate is the most important prognostic marker in Her-2/neu positive tumors, a higher pathologic complete response rate being demonstrated to be associated with a better survival outcome in terms of higher overall survival and disease-free survival rates.

Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures.

Neuronal circuit disturbances that lead to hyperexcitability in the cortico-hippocampal network are one of the landmarks of temporal lobe epilepsy. The dentate gyrus (DG) network plays an important role in regulating the excitability of the entire hippocampus by filtering and integrating information received via the perforant path. Here, we investigated possible epileptogenic abnormalities in the function of the DG neuronal network in the Synapsin II (Syn II) knockout mouse (Syn II(-/-)), a genetic mouse model of epilepsy. Syn II is a presynaptic protein whose deletion in mice reproducibly leads to generalized seizures starting at the age of 2 months. We made use of a high-resolution microelectrode array (4096 electrodes) and patch-clamp recordings, and found that in acute hippocampal slices of young pre-symptomatic (3-6 week-old) Syn II(-/-) mice excitatory synaptic output of the mossy fibers is reduced. Moreover, we showed that the main excitatory neurons present in the polymorphic layer of the DG, hilar mossy cells, display a reduced excitability. We also provide evidence of a predominantly inhibitory regulatory output from mossy cells to granule cells, through feed-forward inhibition, and show that the excitatory-inhibitory ratio is increased in both pre-symptomatic and symptomatic Syn II(-/-) mice. These results support the key role of the hilar mossy neurons in maintaining the normal excitability of the hippocampal network and show that the late epileptic phenotype of the Syn II(-/-) mice is preceded by neuronal circuitry dysfunctions. Our data provide new insights into the mechanisms of epileptogenesis in the Syn II(-/-) mice and open the possibility for early diagnosis and therapeutic interventions.

[Hemostatic hysterectomy in modern obstetrics]. / Histerectomia de hemostaza in obstetrica moderna.

UNLABELLED: Haemostatic hysterectomies have been performed for the first time in the XIXth century to reduce the increased maternal mortality and associated morbidity. In Romania the main cause of death through direct obstetrical risk (DOR) is the haemorrhagic syndrome, with a value of 45% of the total number of deaths in the last 15 -16 years, a lot higher then the world average of 25% as evaluated by OMS. Among the deaths due to hemorrhagic syndrome 43% is held by antepartum haemorrhage (placenta praevia, utero-placental apoplexy) and 42% by postpartum haemorrhage. RESULTS: In the past 15 years (1990 - 2005) there have been studied 53,870 births, out of which only 60 have had haemostatic hysterectomy, representing 0.11% of the total number of births. The prevalence of haemostatic hysterectomy is only 1 in every 883 births as a result of surgical teams' efforts to preserve the uterus. The placental pathology (30%) is responsible for most of haemostatic hysterectomy indications. Out of 60 cases under study, none ended with maternal death, while 11 cases ended with fetal death (intrapartum or postpartum). CONCLUSIONS: Morbidity and maternal death can be reduced by effective prenatal care, by identifying high risk patients and by the possibility of caesarean section. Haemostatic hysterectomy remains, in essence, a life saving procedure!