Activation of the maternal immune system (MIA) during gestation is linked to neuropsychiatric diseases like schizophrenia. While many studies address behavioural aspects, less is known about underlying cellular mechanisms. In the following study, BALB/c mice received intraperitoneal injections of polyinosinic-polycytidylic acid (Poly IC) (20 µg/ml) or saline (0.9%) at gestation day (GD) 9.5 before hippocampal neurons were isolated and cultured from embryonic mice for further analysis. Interestingly, strongest effects were observed when the perineuronal net (PNN) wearing subpopulation of neurons was analysed. Here, a significant reduction of aggrecan staining intensity, area and soma size could be detected. Alterations of PNNs are often linked to neuropsychiatric diseases, changes in synaptic plasticity and in electrophysiology. Utilizing multielectrode array analysis (MEA), we observed a remarkable increase of the spontaneous network activity in neuronal networks after 21 days in vitro (DIV) when mother mice suffered a prenatal immune challenge. As PNNs are associated with GABAergic interneurons, our data indicate that this neuronal subtype might be stronger affected by a prenatal MIA. Degradation or damage of this subtype might cause the hyperexcitability observed in the whole network. In addition, embryonic neurons of the Poly IC condition developed significantly shorter axons after five days in culture, while dendritic parameters and apoptosis rate remained unchanged. Structural analysis of synapse numbers revealed an increase of postsynaptic density 95 (PSD-95) puncta after 14 DIV and an increase of presynaptic vesicular glutamate transporter (vGlut) puncta after 21 DIV, while inhibitory synaptic proteins were not altered.The ability of quinoline alkaloids (cinchonine, cinchonidine, quinine, and quinidine) to sensitize different human cancer cell lines to doxorubicin (DOX)-induced cell death was evaluated. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alkaloids ability to enhance DOX-induced apoptosis was explored using Western blotting analysis. Also, flow cytometry was applied to analyze cell fractions in the different cell cycle phases. All alkaloids showed a significant enhancement of DOX-induced cell death in HeLa and HepG2 cell lines. The chemosensitizing activity of the quinoline alkaloids was attributed to the induction of apoptosis as indicated by splitting of caspase-3 and its substrate poly (ADP-ribose) polymerase (PARP). In addition, there was an increase in the cell fractions in sub-G0/G1 phase in case of DOX combination with the alkaloids. This study proves the ability of the quinoline alkaloids to enhance DOX-induced apoptotic cell death in human cervical and hepatocellular carcinoma cells.
  To explore how workplace bullying influences nurses' abilities to provide patient care.
 
  Nurses' experiences of workplace bullying undermine nursing work environments and potentially threaten patient care. Although there is a link between nurses' experiences of workplace bullying and poor patient care, additional exploration is necessary as current evidence remains underdeveloped and inconclusive.
 
  Qualitative descriptive study.
 
  Fifteen inpatient staff nurses who have experienced workplace bullying while working in one hospital located in the southern region of the USA participated in individual, semi-structured interviews. Inductive thematic analysis was used to analyse interview transcripts in NVivo 12 software. The COREQ checklist for qualitative studies has been used in reporting this study.
 
  Three themes, and respective subthemes, were generated from data analysis (a) workplace bullying as part of the nursing work environment, (b) workplace bullying's influence on nurses and (c) workplace bullying workplace bullying influences their abilities to provide patient care increases our understanding of workplace bullying implications.
 Understanding how nurses perceive the work environment to influence their experiences of workplace bullying informs the development of organisational interventions to reduce the behaviour. Furthermore, exploring how nurses' experiences of workplace bullying influences their abilities to provide patient care increases our understanding of workplace bullying implications.We present the case of 24-year-old woman who presented with chronic headaches with features of raised intracranial pressure and bilateral papilledema. Brain magnetic resonance imaging revealed the characteristic features of idiopathic intracranial hypertension. A diagnosis supported by clinical features and other ancillary tests. These features are important for physicians to recognize early, so that timely treatment may prevent permanent complications from this rare but potentially sight-threatening headache.Recent evidence supports the emerging hypothesis that the amyloid-β precursor protein C-terminal fragments (APP-CTFs) and dysregulations in both their qualitative and quantitative productions may actively and directly contribute to the neuronal toxicity in early phases of Alzheimer's disease (AD). These new findings revealed the urgent needs and gaps in better understanding the metabolism and full spectrum of APP-CTFs. In this study, we characterized by mass spectrometry the full patterns of APP-CTFs in different cell types and in the brain of an AD APPPS1 mouse model. In these systems, we first discovered a series of 71-80 amino acids long N-terminally truncated APP-CTFs of unknown functions. We next demonstrated that these N-terminally truncated APP-CTFs are sequentially produced by the proteolytic processing of APP-C80, by an as yet unidentified protease.  https://www.selleckchem.com/products/pnd-1186-vs-4718.html  Finally, these N-terminally truncated APP-CTFs are likely protein substrates recognized and processed by the γ-secretase complex, leading to the production of N-terminally truncated Aβ peptides. Together, our findings provide new insights into the metabolism of APP and offer potential new strategies to modulate the production of toxic Aβ peptides in AD.
  To provide a descriptive account of the challenges and administrative preparedness for establishing and sustaining safe obstetric services during the COVID-19 pandemic at Topiwala National Medical College & BYL Nair Charitable Hospital (NH), Mumbai, India.
 
  The management of pregnant women with COVID-19 was implemented as per international (WHO, RCOG, ACOG) and national (Indian Council of Medical Research) recommendations and guidelines at an academic, tertiary care, COVID-19 hospital in India.
 
  Using a multidisciplinary approach and active engagement of a multispecialty team, obstetric services were provided to over 400 women with laboratory-confirmed COVID-19. A sustainable model is established for providing services to pregnant women with COVID-19 in Mumbai Metropolitan Region, India.
 
  With limited resources, it is possible to set up dedicated maternity services, aligned to international guidelines, for safe pregnancy outcomes in COVID-19 settings. This COVID-19 hospital addressed the challenges and implemented several known and novel methods to establish and sustain obstetric services for women with COVID-19.