Pregnancy outcome with hepatitis E infection

Background: Hepatitis E is usually a self-limited viral infection in men and non-pregnant women, but during pregnancy it is associated with high maternal and perinatal mortality. This needs to be studied for early diagnosis and better management.Methods: The study commenced after the approval of Institutional Ethics Committee. This was a retrospective cum prospective observational study conducted in the Department of Obstetrics and Gynaecology and Department of Medical Intensive Care Unit in present tertiary care hospital between February 2012 and July 2017. An analysis of 120 cases was made over a period of five years.Results: In this study the incidence of pregnant patients with hepatitis E was 3.09 per 1000 deliveries. It was found that majority of the patients which were diagnosed with hepatitis E were young and belonged to the age group of 21-25 years. Most of the affected patients were primigravida with increasing severity of the disease in their third trimester. The maternal morbidity was 51% with a mortality rate of 20%. The percentage of still birth was 25.64% with increased incidence of preterm deliveries and poor perinatal outcome.Conclusions: Early diagnosis and rapid management of the complications such as correction of abnormal coagulation and supportive management is the best treatment available at present. ICU admission and with strict maternal and foetal monitoring can help improve the outcome and thereby reducing the maternal and perinatal mortality

Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion.

The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001

Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration

BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development. RESULTS: Our results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland. CONCLUSION: Together, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF treatment increases protein citrullination and that PAD2 inhibition blocks EGF-induced cell migration suggest that PAD2 likely functions within the EGF signaling pathway to mediate cell migration

Assessment of Bronchiectasis in HIV Patients among an Urban Population

Bronchiectasis is characterized by permanent destruction of the airways that presents with productive cough, as well as bronchial wall thickening and luminal dilatation on computed tomographic (CT) scan of the chest; it is associated with high mortality. Accumulating data suggests higher rates of bronchiectasis among the HIV-positive population. This case series involves 14 patients with bronchiectasis and HIV followed at two major urban institutions from 1999 to 2018. Demographics, clinical presentation, microbiology, radiographic imaging, and outcomes were collected and compiled. Mean age was 42 years (range 12-77 years). 36% had a CD4 count greater than 500 cells/mm3, 28% had a CD4 count between 200 and 500 cells/mm3, and 36% had AIDS. 43% were treated for Pneumocystis jiroveci pneumonia (PJP) and 50% for Mycobacterium avium complex (MAC) infection. 21% had COPD, 7% had asthma, and 7% had a history of pulmonary aspergillosis. Two patients were followed up by pulmonary services after diagnosis of bronchiectasis on CT. The timeline of the follow-up in these cases was within months and after three years respectively. It is posited that the prevalence of bronchiectasis in HIV patients may be underestimated. Improving recognition and management of bronchiectasis could help diminish rehospitalization rates

Blockchain-Based Secure Voting Mechanism Underlying 5G Network: A Smart Contract Approach

Purpose: With the advancement and modernization of Information and Communication Technology, electronic voting (e-voting) has been adopted across the globe for conducting a secure and efficient voting procedure. However, e-voting can be easily exposed to various malicious attacks such as denial-of-service, malware, insider, compromised credentials, etc., that can risk the voter’s privacy and affect the final voting results. Thus, we have considered the decentralized and immutable blockchain technology for completing the voting procedure securely. Nevertheless, many researchers have considered blockchain to mitigate the security and privacy issues of the voting procedure, but they ignored the aspect of cost-efficiency, latency, and response time while voting. Method: The idea of the proposed mechanism is to deploy and implement the smart contract in the Remix Integrated Development Environment (IDE) involving number of voters electing the candidate with various functionalities. Moreover, we considered the amalgamation of blockchain and IPFS to overcome the data storage cost issues of blockchain for voters and candidates communicating through 5G wireless network. The 5G network, with its low latency, high availability, and high reliability facilitates high data rate and reliable communication between voters and candidates to complete the voting procedure efficiently. Results: The deployed smart contract of the proposed voting mechanism highlight various functionalities required for electing the candidate by the voters. Moreover, the deployed smart contract is evaluated and analyzed considering various performance metrics such as gas consumption analysis for smart contract functions and number of voters, cost analysis for smart contract functions, bit error rate, and storage cost comparison with the traditional scheme. We have also verified the security of the proposed voting mechanism using Echidna security tool which shows the election of candidate without any threat. Conclusion: Finally, we have presented a blockchain-based voting mechanism in which IPFS and 5G is employed to avail the cost-efficient, reliable, and secure candidate election by the voters. Moreover, the voters and candidates can communicate with lower response time and high reliability using 5G network so that smart contract consisting of all the functionalities related to the candidate election can be executed efficiently in the Remix IDE

Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion.

The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001

Additional file 2: Fig. S1. of Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration

Depletion of PAD2 suppresses the ability of MCF10DCIS.com cells to form foci. Representative image of crystal violet stained MCF10DCIS.com scrambled-shRNA and PADI2-shRNA cells grown for 1-week. (PDF 3631 kb

Additional file 1: Fig. S2. of Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration

PAD2 overexpression increases the migratory potential of MCF10AT cells. Relative average areas of wound closure from the wound healing assays (n = 6) were calculated using ImageJ and normalized to empty vector controls (* p < 0.05). (PDF 690 kb