Management of birth, postpartum care and breastfeeding — Polish recommendations and guidelines during SARS-CoV-2 pandemic

SARS-CoV-2 pandemic is an unusual phenomenon in the modern obstetric and midwifery history. Hospital staff from the isolation wards were trained in the safety and proper use of the hazardous materials suit and the proper managing of the biohazard materials. We were not expecting the situation, so we started to create more restrictions than facilities for mothers giving birth. In the context of infection risk for the fetus, scientists still search for vertical transmission evidence, but available data are ambiguous, and more research is needed. Concerning the infant safety and to minimalize the infection risk for medical teams, the first Polish guidelines published by the national consultants in obstetrics, midwifery, neonatology, and perinatology regarding the safest formula of birth were as the following: in the case of confirmed SARS-CoV-2 infection, the cesarean section for epidemic indications should be considered, except in an advanced or rapid labor. In the lately updated consensus (14th May), it was written that because the risk of vertical and intranatal SARS-CoV-2 transmission seemed to be low, the SARS-CoV-2 infection was not the main indication to perform cesarean section for any longer. Regardless of the birth formula, the newborns are separated from their mothers immediately after the labor in Polish obstetrician hospitals. The Polish Lactation Study Centre, consociating International Breastfeeding Certified Lactation Consultant, recommends feeding the newborn with its own mother’s milk, even if she is infected with SARS-CoV-2 and isolated from her infant

Clinical and genetic characterization of adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation

Background and purpose: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. Methods: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. Results: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18–78 years), the mean age at death was 53 years (range 23–84 years) and the mean disease duration was 6.8 years (range 1–29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158–11.177). There was an age‐dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion‐restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy‐nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype−genotype correlations. Conclusions: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex

Rusty pipe syndrome. Safety of breastfeeding

The rusty pipe syndrome is an uncommon condition. It is characterised by suddenly painless, bilateral bloody nipple discharge with no visible evidence of mechanical injuries within the breasts. It resolves spontaneously with no additional medical intervention. If the problem persists for more than 5–7 days, further investigations should be made to exclude other pathologies. In the available literature, there is no clear explanation of the condition. Many authors agree that the condition may be caused by the structure of blood vessels and may depend on changes therein that occur during stage I and II lactogenesis. In most cases, it is recognised during breast milk expression, when the colour of milk is different than normally

Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.

OBJECTIVE: To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD). METHODS: Clinical investigation was made of available family members, including historical and chart reviews. Subject examinations were video recorded. Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis. RESULTS: We evaluated 32 individuals, of whom 6 were clinically diagnosed with DRD, with childhood-onset progressive foot dystonia, later generalizing, followed by parkinsonism in the two older patients. The response to levodopa was very good. Two additional patients had late onset dopa-responsive parkinsonism. Three other subjects had DRD symptoms on historical grounds. We found suggestive linkage to the previously reported DYT14 locus, which excluded GCH1. However, further study with more stringent criteria for disease status attribution showed linkage to a larger region, which included GCH1. No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1. The mutation was found in seven subjects. One of the patients with dystonia represented a phenocopy. CONCLUSIONS: This study rules out the previously reported DYT14 locus as a cause of disease, as a novel multiexonic deletion was identified in GCH1. This work highlights the necessity of an accurate clinical diagnosis in linkage studies as well as the need for appropriate allele frequencies, penetrance, and phenocopy estimates. Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis

Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis.

Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression of bladder cancer. To study its contribution to bladder cancer metastasis, we established new xenograft models derived from human bladder cancer cell lines utilizing an orthotopic "recycling" technique that allowed us to isolate and examine the primary tumor and its corresponding circulating tumor cells (CTC's) and metastatic lesions. Using whole genome mRNA expression profiling, we found that a reversible epithelial-to-mesenchymal transition (EMT) characterized by TGFβ pathway activation and SNAIL expression was associated with the accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL completely blocked CTC production and regional/distant metastasis. Using this unique bladder cancer xenograft model, we conclude that metastasis is dependent on a reversible EMT mediated by SNAIL

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Peripartum prolactin and cortisol level changes. A prospective pilot study

Although the role of prolactin and cortisol in the human lactation process seems to be undisputed, the changes in postpartum serum concentrations in mothers make data interpretation difficult. To determine the factors that possibly influence these hormones, we examined a group of patients who were admitted to the Gynecology-Obstetrics Clinical Hospital in Poznan for labor induction and/or in the active phase of the first labor period. The serum levels of cortisol and prolactin were assessed in these full-term pregnant women during admission to labor, in the third stage of labor, and on the second day postpartum. The prolactin and cortisol levels were also measured in the umbilical cord for the assessment of newborn babies. The results showed a significant relationship between maternal age and the level of prolactin measured before childbirth and fluctuations in cortisol level with respect to labor duration. In addition, we observed a strong correlation between the level of prolactin assessed before childbirth and the pH and base excess of the umbilical cord artery. Most importantly, a correlation was noted between breastfeeding within two hours after the labor and the level of cortisol measured after childbirth, which is worth mentioning to emphasize the significance of early maternal–neonatal skin-to-skin contact

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1