Metal regulation of Mycobacterium tuberculosis SufB intein splicing at the host-pathogen crossroad.

Intein sequences self-excise from precursor proteins to generate functional proteins in various organisms. Thus, regulation of intein splicing at the host-pathogen interface can determine the fate of infection by controlling generation of essential proteins in microbes. For instance, Mycobacterium tuberculosis (Mtu) SufB intein splicing is crucial for the functionality of SUF complex. This multiprotein system is the sole pathway for [Fe-S] cluster biogenesis in mycobacteria during oxidative stress and Fe starvation. Although metal toxicity and metal starvation are components of host immunity, correlation of metal stress to Mtu SufB intein splicing is missing till date. Current study examines the splicing and N-terminal cleavage reactions of Mtu SufB precursor protein in presence of micronutrient metal ions like Zn+2, Cu+2, and Fe+3/+2. A known intein splicing inhibitor Pt+4 was also tested to support its proposed role as an anti-TB agent. Mtu SufB precursor protein exhibited significant attenuation of splicing and N-terminal cleavage reactions across different concentration ranges for Pt+4, Cu+2, Zn+2, while Fe+3 interaction resulted in precursor accumulation. UV-Vis spectroscopy, inductively coupled plasma-optical emission spectroscopy (ICP-OES), Tryptophan fluorescence assay, and dynamic light scattering (DLS) techniques analyzed metal-protein interaction. Mutagenesis experiments and Ellman's assay identified plausible metal co-ordination sites within Mtu SufB protein. Analyzing the metal effect on Mtu SufB splicing may provide elemental information about the fate of mycobacterial infection, and a probable mechanism to attenuate intracellular survival of Mtu. Current research hints at the host regulatory mechanism on SufB splicing in its native environment and a likely target for developing next-generation anti-TB drugs.

Factors associated with cesarean birth in nulliparous women: A multicenter prospective cohort study.

BACKGROUND: There is widespread concern around the rising rates of cesarean births (CBs), especially among first-time mothers, despite evidence suggesting increased morbidities after birth by cesarean. There are uncertainties around factors associated with rising rates of CBs among first-time mothers in Ireland, and insight into these is essential for understanding the rising trend in CBs. Therefore, this study aimed to identify the factors associated with CBs in nulliparous women. METHODS: A prospective cohort study was conducted in three maternity hospitals in the Republic of Ireland between 2012 and 2017. Data were collected from 3047 nulliparous women using self-administered surveys antenatally and at 3 months postpartum and from consenting women's hospital records (n = 2755) and analyzed using the Poisson regression to assess associations between demographic and clinical factors and the main outcome measures, planned and unplanned CBs. RESULTS: Common risk factors for planned and unplanned CBs were being aged ≥40 years, being in private care, multiple pregnancy, and fetus in breech or other malpresentations. An unplanned CB occurred for 22.43% (n = 377/1681) of women who did not have induction of labor (IOL) or who had IOL with no epidural, but the risk was about twice as high for women who had IOL and epidural. CONCLUSIONS: Findings confirm multifactorial reasons for CB and the challenge of reversing the increasing CB rate if maternal age, overweight/obesity, infertility treatment, multiple pregnancy, and preexisting hypertension in Ireland continue to increase. There is a need to address prelabor interventions, especially IOL combined with epidural analgesia with respect to unplanned CB.

A systematic review of utility-based and disease-specific quality of life measurement instruments for women with urinary incontinence.

AIM: This systematic review aims to identify disease-specific and generic quality of life (QoL) outcome measurement instruments used in populations of women with urinary incontinence (UI) and to determine the most psychometrically robust and appropriate disease-specific and generic tools for measuring the quality of life in this population. METHODS: A systematic search was conducted of PubMed, Embase, SCIELO, and CINAHL databases for studies evaluating measurement properties of QoL instruments in women with UI. The methodological quality of studies and the quality of measurement properties were evaluated using the COnsensus-based Standards for the selection of health status Measurement INtruments (COSMIN) checklist and quality criteria. Overall, evidence for measurement properties was graded using the modified grading of recommendations, assessment, development & evaluation approach. RESULTS: A total of 73 studies were included, and 27 specific and 6 generic instruments were identified. The Incontinence QoL questionnaire (IQoL) had the highest overall psychometric quality for English-speaking populations and was the most widely translated tool. Evidence for generic QoL tools in this population is limited. Few studies evaluated measurement error or cross-cultural validity. CONCLUSION: The IQoL is the most psychometrically robust disease-specific tool for use in this population. More research is needed to determine the most psychometrically robust generic tool. Future studies should also evaluate measurement error and cross-cultural validity as evidence for these properties is particularly lacking.

Factors influencing decision-making for caesarean section in Sweden - a qualitative study.

BACKGROUND: Rising rates of caesarean section (CS) are a concern in many countries, yet Sweden has managed to maintain low CS rates. Exploring the multifactorial and complex reasons behind the rising trend in CS has become an important goal for health professionals. The aim of the study was to explore Swedish obstetricians' and midwives' perceptions of the factors influencing decision-making for CS in nulliparous women in Sweden. METHODS: A qualitative design was chosen to gain in-depth understanding of the factors influencing the decision-making process for CS. Purposive sampling was used to select the participants. Four audio-recorded focus group interviews (FGIs), using an interview guide with open ended questions, were conducted with eleven midwives and five obstetricians from two selected Swedish maternity hospitals after obtaining written consent from each participant. Data were managed using NVivo© and thematically analysed. Ethical approval was granted by Trinity College Dublin. RESULTS: The thematic analysis resulted in three main themes; 'Belief in normal birth - a cultural perspective'; 'Clarity and consistency - a system perspective' and 'Obstetrician makes the final decision, but...', and each theme contained a number of subthemes. However, 'Belief in normal birth' emerged as the core central theme, overarching the other two themes. CONCLUSION: Findings suggest that believing that normal birth offers women and babies the best possible outcome contributes to having and maintaining a low CS rate. Both midwives and obstetricians agreed that having a shared belief (in normal birth), a common goal (of achieving normal birth) and providing mainly midwife-led care within a 'team approach' helped them achieve their goal and keep their CS rate low.

Multi-factor optimized mobile sink data collection framework for hybrid WSN-LTE assisted IoT network.

The convergence of wireless sensor network-assisted Internet of Things has diverse applications. In most applications, the sensors are battery-powered, and it is necessary to use the energy judiciously to extend their functional duration effectively. Mobile sinks-based data collection is used to extend the lifespan of these networks. But providing a scalable and effective solution with consideration for multi-criteria factors of quality of service and lifetime maximization is still a challenge. This work addresses this problem with a hybrid wireless sensor network-Long term evolution assisted architecture. The problem of maximizing lifetime and providing multi-factor quality of service is solved as a two-stage optimization problem involving clustering and data collection path scheduling. Hybrid meta-heuristics is used to solve the clustering optimization problem. Minimal Steiner tree-based graph theory is applied to schedule the data collection path for sinks. Unlike existing works, the lifetime maximization without QoS degradation is addressed by hybridizing multiple approaches of multi-criteria optimal clustering, optimal path scheduling, and network adaptive traffic class-based data scheduling. This hybridization helps to extend the lifetime and enhance the QoS regarding packet delivery within the proposed solution. Through simulation analysis, the introduced approach yields a noteworthy increase of at least 6% and reduces packet delivery delay by 26% compared to existing methodologies.

Fathers' experiences, views and perspectives of childbirth attendance: A qualitative evidence synthesis protocol.

Background: The involvement of husbands and male partners in childbirth no longer ceases at conception and pregnancy, rather fathers wish to be more involved in supporting their partners during childbirth. This aligns with the World Health Organization's (WHO) call for promoting male participation in childbirth, emphasising the benefits of support and the positive impact attending childbirth has for husbands/partners, and their maternal partner. This knowledge has led to global initiatives promoting "humanised" birth and a family-approach. To gain in-depth insight and understanding of childbirth attendance from the perspectives of fathers, a qualitative evidence synthesis is proposed. Methods: To explore fathers' experiences, views, and perspectives of childbirth attendance. All studies that used qualitative methodologies to explore the phenomenon of interest will be included. MEDLINE, CINAHL, PsycINFO, MIDIRS, Web of Science, and Google Scholar will be systematically searched from their dates of inception to present, supplemented by a search for grey literature and a search of the reference list of included studies. Peer Review of Electronic Search Strategies (PRESS) will be used to ensure the comprehensiveness of the search strategy. Methodological quality assessment of included studies, using The Critical Appraisal Skills Programme assessment tool, and will be extracted from the included studies by two reviewers independently using a standard data extraction form. Thomas and Harden's three-stage approach will be used to thematically synthesise the data: coding of data, developing descriptive themes, and generation of analytical themes. The Grading of Recommendations Assessment, Development, and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual confidence in the synthesised findings Comprehensive insight and understanding of fathers' perspectives of childbirth attendance will be ascertained. PROSPERO Registration No: CRD42023470902.

Mucormycosis: A Rare disease to Notifiable Disease.

Mucormycosis is the third most frequent invasive mycosis, following candidiasis and aspergillosis. It is frequently neglected due to its rare occurrence; but recently attend the status of notifiable disease due to its higher incidence in both developed and developing nations. India has received global notice since its estimated instances were greater than the global estimated figures. Mucormycosis has several clinical manifestations, including rhino-orbital-cerebral (ROCM), pulmonary, gastrointestinal, cutaneous, renal, and diffuse Mucormycosis. ROCM is the most frequent clinical manifestation in India, although pulmonary mucormycosis is prevalent worldwide. This review also discusses host defenses, pre disposing risk factors and fungal virulence factors that impair host's ability to prevent fungus invasion and disease establishment. The diagnosis of the disease depends on clinical interventions, histological or microbiological procedures along with molecular methods to obtain timely results. But there are still unmet challenges for rapid diagnosis of the disease. Treatment of the disease is achieved by multimodal approaches such as reversal of underlying predisposing factors, rapid administration of antifungals in optimal doses and surgical procedures to remove infected tissues. Liposomal Amphotericin B, Posaconazole and Isavuconazoles are preferred as the first line of treatment procedures. clinical trials. Different studies have improved the existing drug and under clinical trials while several studies predicted the new potential targets as CotH and Ftr1 as shown in infection and in vitro models. Therefore, current scenario demands a multidisciplinary approach is needed to investigate the prevalence, pathogenesis which is highly important for the advancement of rapid diagnosis and effective treatment.

Lipid and cholesterols modulate the dynamics of SARS-CoV-2 viral ion channel ORF3a and its pathogenic variants.

SARS-CoV-2 accessory protein, ORF3a is a putative ion channel which immensely contributes to viral pathogenicity by modulating host immune responses and virus-host interactions. Relatively high expression of ORF3a in diseased individuals and implication with inflammasome activation, apoptosis and autophagy inhibition, ratifies as an effective target for developing vaccines and therapeutics. Herein, we present the elusive dynamics of ORF3a-dimeric state using all-atoms molecular dynamics (MD) simulations at µ-seconds scale in a heterogeneous lipid-mimetic system in multiple replicates. Additionally, we also explore the effect of non-synonymous pathogenic mutations on ORF3a ion channel activity and viral pathogenicity in different SARS-CoV-2 variants using various structure-based protein stability (ΔΔG) tools and computational saturation mutagenesis. Our study ascertains the role of phosphatidylcholines and cholesterol in modulating the structure of ORF3a, which perturbs the size and flexibility of the polar cavity that allows permeation of large cations. Discrete trend in ion channel pore radius and area per lipid arises the premise that presence of lipids might also affect the overall conformation of ORF3a. MD structural-ensembles, in some replicates rationalize the crucial role of TM2 in maintaining the native structure of ORF3a. We also infer that loss of structural stability primarily grounds for pathogenicity in more than half of the pathogenic variants of ORF3a. Overall, the effect of mutation on alteration of ion permeability of ORF3a, proposed in this study brings mechanistic insights into variant consequences on viral membrane proteins of SARS-CoV-2, which can be utilized for the development of novel therapeutics to treat COVID-19 and other coronavirus diseases.

Computational saturation mutagenesis to explore the effect of pathogenic mutations on extra-cellular domains of TREM2 associated with Alzheimer's and Nasu-Hakola disease.

CONTEXT: The specialised family of triggering receptors expressed on myeloid cells (TREMs) plays a pivotal role in causing neurodegenerative disorders and activating microglial anti-inflammatory responses. Nasu-Hakola disease (NHD), a rare autosomal recessive disorder, has been associated with mutations in TREM2, which is also responsible for raising the risk of Alzheimer's disease (AD). Herein, we have made an endeavour to differentiate the confirmed pathogenic variants in TREM2 extra-cellular domain (ECD) linked with NHD and AD using mutation-induced fold stability change (∆∆G), with the computation of 12distinct structure-based methods through saturation mutagenesis. Correlation analysis between relative solvent accessibility (RSA) and ∆∆G expresses the discrete distributive behaviour of mutants associated with TREM2 in AD (R2 = 0.061) and NHD (R2 = 0.601). Our findings put an emphasis on W50 and V126 as major players in maintaining V-like domain in TREM2. Interestingly, we discern that both of them interact with a common residue Y108, which is dissolved upon mutation. This Y108 could have structural or functional role for TREM2 which can be an ideal candidate for further study. Furthermore, the residual interaction network highlights the importance of R47 and R62 in maintaining the CDR loops that are crucial for ligand binding. Future studies using biophysical characterisation of ligand interactions in TREM2-ECD would be helpful for the development of novel therapeutics for AD and NHD. METHODS: ConSurf algorithm and ENDscript were used to determine the position and conservation of each residue in the wild-type ECD of TREM2. The mutation-induced fold stability change (∆∆G) of confirmed pathogenic mutants associated with NHD and AD was estimated using 12 state-of-the-art structure-based protein stability tools. Furthermore, we also computed the effect of random mutation on these sites using computational saturation mutagenesis. Linear regression analysis was performed using mutants ∆∆G and RSA through GraphPad software. In addition, a comprehensive non-bonded residual interaction network (RIN) of wild type and its mutants of TREM2-ECD was enumerated using RING3.0.

Molecular docking and MD simulations reveal protease inhibitors block the catalytic residues in Prp8 intein of Aspergillus fumigatus: a potential target for antimycotics.

Resistance to azoles and amphotericin B especially in Aspergillus fumigatus is a growing concern towards the treatment of invasive fungal infection. At this critical juncture, intein splicing would be a productive, and innovative target to establish therapies against resistant strains. Intein splicing is the central event for the activation of host protein, essential for the growth and survival of various microorganisms including A. fumigatus. The splicing process is a four-step protease-like nucleophilic cascade. Thus, we hypothesise that protease inhibitors would successfully halt intein splicing and potentially restrict the growth of the aforementioned pathogen. Using Rosetta Fold and molecular dynamics simulations, we modelled Prp8 intein structure; resembling classic intein fold with horse shoe shaped splicing domain. To fully comprehend the active site of Afu Prp8 intein, C1, T62, H65, H818, N819 from intein sequences and S820, the first C-extein residue are selected. Molecular docking shows that two FDA-approved drugs, i.e. Lufotrelvir and Remdesivir triphosphate efficiently interact with Prp8 intein from the assortment of 212 protease inhibitors. MD simulation portrayed that Prp8 undergoes conformational change upon ligand binding, and inferred the molecular recognition and stability of the docked complexes. Per-residue decomposition analysis confirms the importance of F: block R802, V803, and Q807 binding pocket in intein splicing domain towards recognition of inhibitors, along with active site residues through strong hydrogen bonds and hydrophobic contacts. However, in vitro and in vivo assays are required to confirm the inhibitory action on Prp8 intein splicing; which may pave the way for the development of new antifungals for A. fumigatus.Communicated by Ramaswamy H. Sarma.

Voice from the frontline and learning for the future: A qualitative descriptive study on wider perspectives of frontline nurses in India during the COVID 19 global pandemic.

Objective: This study was conducted to explore frontline nurses' experiences of the impact of COVID 19 pandemic and suggestions for improvement in the healthcare system, policy and practice in the future. Method: A qualitative descriptive design was used. Frontline nurses who were involved in providing care to patients affected with COVID 19 in four designated COVID units from the Eastern, Southern and Western regions of India were interviewed during January to July 2021. Interviews were audio-recorded and transcribed manually by researchers from each region and thematically analysed. Result: Twenty-six frontline nurses aged between 22 and 37 years with a range of 1-14 years of work experience following a Diploma or Bachelor's degree in Nursing and Midwifery and working in the COVID units of selected regions in India participated in the study. Three key themes emerged: 'Physical, emotional and social health - an inevitable impact of the pandemic' described effects of the pandemic on nurses' health and wellbeing; 'Adapting to the uncertainties' narrated how nurses accommodated to the uncertainties during the pandemic; and 'An agenda for the future - suggestions for improvement' emphasised on practical strategies for the future. Conclusion: The inevitability of the pandemic had an influence at a personal, professional, and social level with learning for the future. The findings of this study have implications for healthcare system and facilities by enhancing resources, supportive environment for staffs to cope with the challenges imposed by the crisis and ongoing training to manage life threatening emergencies in the future.

An immunoinformatic approach towards development of a potent and effective multi-epitope vaccine against monkeypox virus (MPXV).

Monkeypox is a viral zoonotic disease, often transmitted to humans from animals. While the whole world is haggling with the COVID-19 pandemic, the emergence of the monkeypox virus (MPXV) arose as a new challenge to mankind. Till date, numerous cases related to the MPXV have been reported in several countries across the globe, but, its momentary distribution in the current time has left everyone in fright with increasing mortality and limited clinically approved treatments. Therefore, it is of immense importance to develop a potent and highly effective vaccine capable of inducing desired immunogenic responses against the highly contagious MPXV. Herein, using various immunoinformatic and computational biology tools, we made an attempt to develop a multi-epitope vaccine construct against the MPXV which is antigenic, non-allergen and non-toxic in nature and capable of exhibiting immunogenic behavior. The sequence of vaccine construct was designed using the proposed 4 MHC-I, 3 MHC-II and 4 B-cell epitopes linked with suitable adjuvant and linkers. The modeled structure of the vaccine construct was used to assess its interaction with the Toll-like Receptor 4 (TLR4) using ClusPro and HADDOCK. All-atoms molecular dynamics simulation of the MPXV vaccine construct-TLR4 complex followed by a high level of gene expression of the construct within the bacterial system affirmed its stability along with induction of immunogenic response within the host cell. Altogether, our immunoinformatic approach aid in the development of a stable chimeric vaccine construct against MPXV and needs further experimental validation for its immunological relevance and usefulness as a vaccine candidate.Communicated by Ramaswamy H. Sarma.

Effectiveness of health literacy and relaxing music on quality of sleep and risk for antenatal depression.

Background: Pregnant women experience increased sleep disturbances during the third trimester of their pregnancy, which may result in the development of psychological issues in the perinatal period. There is a dearth of interventional studies that combine health literacy and the provision of music for the benefit of pregnant women in South Asia. Aim: To determine the effectiveness of a combination of Comprehensive Health literacy And Relaxing Music (CHARM) interventions on quality of sleep and risk for antenatal depression among women visiting antenatal outpatient departments of a tertiary hospital in South India. Methods: A four-arm parallel-group randomized controlled trial was adopted; 128 low-risk primigravid women were recruited and randomly assigned to the four groups using block randomization. The interventions included relaxing music interventions, comprehensive health-literacy interventions, combinations of both as CHARM interventions, and standard antenatal care. All the interventions were provided for four weeks. The quality of sleep among pregnant women was assessed using the Pittsburgh Sleep Quality Index Scale at baseline and after four weeks of intervention. Women at risk of developing antenatal depression were screened using the Edinburgh Postnatal Depression Scale-Antenatal Version. Results: Pregnant women who received CHARM interventions had significant improvement in quality of sleep when compared with other interventions (F(3,124) =15.0, P < .001, effect size η p2= 0.27). Also, 38 (29.6%) of the included pregnant women were at risk of developing antenatal depression, which was reduced to 21 (16.4%) following the intervention. Conclusion: CHARM intervention could promote quality sleep and reduce the risk of developing antenatal depression, thereby improving perinatal mental health.

Indian Biosimilars and Vaccines at Crossroads-Replicating the Success of Pharmagenerics.

BACKGROUND: The global pharma sector is fast shifting from generics to biologics and biosimilars with the first approval in Europe in 2006 followed by US approval in 2015. In the form of Hepatitis B vaccine, India saw its first recombinant biologics approval in 2000. Around 20% of generic medications and 62% of vaccines are now supplied by the Indian pharmaceutical industry. It is this good position in biologics and biosimilars production that could potentially improve healthcare via decreased treatment cost. India has witnessed large investments in biosimilars over the years. Numerous India-bred new players, e.g., Enzene Biosciences Ltd., are keen on biosimilars and have joined the race alongside the emerging giants, e.g., Biocon and Dr. Reddy's. A very positive sign was the remarkable disposition during the COVID-19 pandemic by Bharat Biotech and the Serum Institute of India. India's biopharmaceutical industry has been instrumental in producing and supplying preventives and therapeutics to fight COVID-19. Despite a weak supply chain and workforce pressure, the production was augmented to provide reasonably priced high-quality medications to more than 133 nations. Biosimilars could cost-effectively treat chronic diseases involving expensive conventional therapies, including diabetes, respiratory ailments, cancer, and connective tissue diseases. Biologics and biosimilars have been and are being tested to treat and manage COVID-19 symptoms characterized by inflammation and respiratory distress. PURPOSE OF REVIEW: Although India boasts many universities, research centers, and a relatively skilled workforce, its global University-Industry collaboration ranking is 24, IPR ranking remains 47 and innovation ranking 39. This reveals a wide industry-academia gap to bridge. There are gaps in effective translational research in India that must be promptly and appropriately addressed. Innovation demands strong and effective collaborations among universities, techno-incubators, and industries. METHODOLOGY: Many successful research findings in academia do not get translation opportunities supposedly due to low industrial collaboration, low IP knowledge, and publication pressure with stringent timelines. In light of this, a detailed review of literature, including policy papers, government initiatives, and corporate reviews, was carried out, and the compilation and synthesis of the secondary data were meticulously summarized for the easy comprehension of the facts and roadmap ahead. For easy comprehension, charts, figures, and compiled tables are presented. RESULTS: This review assesses India's situation in the biosimilar space, the gaps and areas to improve for Indian investment strategies, development, and innovation, addressing need for a more skilled workforce, industrial collaboration, and business models. CONCLUSIONS: This review also proposes forward an approach to empowering technopreneurs to develop MSMEs for large-scale operations to support India in taking innovative thoughts to the global level to ultimately realize a self-reliant India. The limitations of the compilation are also highlighted towards the end.

Machine learning and classical MD simulation to identify inhibitors against the P37 envelope protein of monkeypox virus.

Monkeypox virus (MPXV) outbreak is a serious public health concern that requires international attention. P37 of MPXV plays a pivotal role in DNA replication and acts as one of the promising targets for antiviral drug design. In this study, we intent to screen potential analogs of existing FDA approved drugs of MPXV against P37 using state-of-the-art machine learning and computational biophysical techniques. AlphaFold2 guided all-atoms molecular dynamics simulations optimized P37 structure is used for molecular docking and binding free energy calculations. Similar to members of Phospholipase-D family , the predicted P37 structure also adopts a ß-α-ß-α-ß sandwich fold, harbouring strongly conserved HxKxxxxD motif. The binding pocket comprises of Tyr48, Lys86, His115, Lys117, Ser130, Asn132, Trp280, Asn240, His325, Lys327 and Tyr346 forming strong hydrogen bonds and dense hydrophobic contacts with the screened analogs and is surrounded by positively charged patches. Loops connecting the two domains and C-terminal region exhibit high degree of flexibility. In some structural ensembles, the partial disorderness in the C-terminal region is presumed to be due to its low confidence score, acquired during structure prediction. Transition from loop to ß-strands (244-254 aa) in P37-Cidofovir and its analog complexes advocates the need for further investigations. MD simulations support the accuracy of the molecular docking results, indicating the potential of analogs as potent binders of P37. Taken together, our results provide preferable understanding of molecular recognition and dynamics of ligand-bound states of P37, offering opportunities for development of new antivirals against MPXV. However, the need of in vitro and in vivo assays for confirmation of these results still persists.Communicated by Ramaswamy H. Sarma.

Effectiveness of Music on Perinatal Anxiety Among Pregnant Women and Newborn Behaviors: A Systematic Review and Narrative Synthesis.

Background: Perinatal anxiety affects the antenatal woman, the growing fetus, and the newborn. This systematic review evaluated the effect of listening to music on perinatal anxiety among pregnant women and on newborn behaviors. No available reviews focus on interventions that include only classical forms of music or its benefit on perinatal anxiety among low-risk pregnant women or on newborn behaviors. Methods: We included peer-reviewed primary research studies on the effect of music on perinatal anxiety, published in English, between January 2010 and August 2022. PubMed, Embase, Scopus, and ProQuest were searched using specific keywords, resulting in 225 studies for screening by title, abstract, and full text. Two independent reviewers screened them and assessed the quality of the included randomized controlled trials (RCTs) using Cochrane's Risk of Bias 2.0 tool (RoB2) and non-randomized controlled trial studies using the Joanna Briggs Institute Critical Appraisal tool. Due to the heterogeneity of outcome measures, the review's findings were summarized qualitatively. Results: Nine studies with 1646 pregnant women and one with 260 pregnant women and their neonates were included. Results of all studies suggest that listening to classical music reduces the anxiety levels among pregnant women, as measured by the State-Trait Anxiety Inventory (STAI). Only one study reported the beneficial effect of antenatal exposure to music on improving newborn behaviors like orientation (ES 1.13, 95% CI: 0.82-1.44, P < 0.0001) and habituation (ES 1.05, 95% CI: 0.53-1.57, P = 0.0001). The risk of bias was unclear in most of the studies. Conclusions: Listening to classical music during the perinatal period may be an effective non-pharmacological intervention for reducing anxiety and pain and improving sleep quality and newborn behaviors. There is a need to conduct further interventional studies on the types of music provided and their effects on perinatal health outcomes. Registration of the Protocol: The review was prospectively registered in PROSPERO 2021 CRD42021256806.

Clinicians' views of factors influencing decision-making for CS for first-time mothers-A qualitative descriptive study.

Clinicians' perspectives of the reasons for performing caesarean section (CS) are fundamental to deepening knowledge and understanding of factors influencing decision-making for CS. The aim of this study was to explore midwives' and obstetricians' views of factors influencing decision-making for CS for first-time mothers. A qualitative descriptive study with semi-structured one-to-one audio-recorded interviews was used to gather data from clinicians (15 midwives and 20 senior obstetricians). Following research ethics committee approval, clinicians, who were directly involved in the decision-making process for CS during the period of data collection, were purposively selected from three maternity units in the Republic of Ireland between June 2016 to July 2017. The interviews were transcribed verbatim and analysed thematically. Three interrelated themes with several subthemes reflective of clinicians' views and experiences emerged following data analysis. These were: 'A fear factor' describing clinicians' fear of adverse outcomes and subsequent litigation, 'Personal preferences versus a threshold-clinician driven factors emphasising the influence of clinicians' personal beliefs, and 'Standardised versus individualised care-a system perspective' explaining the effects of, or lack of, organisational policy and its direct and indirect impact on the decision-making process. Findings show that decisions to perform a CS are, on occasion, based on clinicians' personal beliefs and interpretation, similar to findings from other published literature. Consideration of broader issues related to organisational, socio-cultural and political context is essential when seeking solutions to the rising CS rates. The findings will enable clinicians to reflect on their day-to-day practice, in order to look for modifiable factors that influence their decision-making, and help women understand the multitude of factors that can lead to a decision to perform a CS. Findings will also contribute to the development of the 'next step action' and assist in devising future intervention studies to reduce any unnecessary CSs.

SufB intein splicing in Mycobacterium tuberculosis is influenced by two remote conserved N-extein histidines.

Inteins are auto-processing domains that implement a multistep biochemical reaction termed protein splicing, marked by cleavage and formation of peptide bonds. They excise from a precursor protein, generating a functional protein via covalent bonding of flanking exteins. We report the kinetic study of splicing and cleavage reaction in [Fe-S] cluster assembly protein SufB from Mycobacterium tuberculosis (Mtu). Although it follows a canonical intein splicing pathway, distinct features are added by extein residues present in the active site. Sequence analysis identified two conserved histidines in the N-extein region; His-5 and His-38. Kinetic analyses of His-5Ala and His-38Ala SufB mutants exhibited significant reductions in splicing and cleavage rates relative to the SufB wildtype (WT) precursor protein. Structural analysis and molecular dynamics (MD) simulations suggested that Mtu SufB displays a unique mechanism where two remote histidines work concurrently to facilitate N-terminal cleavage reaction. His-38 is stabilized by the solvent-exposed His-5, and can impact N-S acyl shift by direct interaction with the catalytic Cys1. Development of inteins as biotechnological tools or as pathogen-specific novel antimicrobial targets requires a more complete understanding of such unexpected roles of conserved extein residues in protein splicing.

Women's views and experiences of maternity care during COVID-19 in Ireland: A qualitative descriptive study.

OBJECTIVE: To gain insight and understanding of women's views and experiences of maternity care during the COVID-19 pandemic in Ireland. DESIGN: A qualitative descriptive study using semi-structured interviews. Due to social distancing and associated COVID-19 restrictions at the time of the study, the interviews were held remotely via telephone. The interviews were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the interview data. SETTING & PARTICIPANTS: A large urban tertiary referral maternity unit (greater than 8000 births per year) in the Republic of Ireland. Women of low and high obstetric risk, primiparous and multiparous, who gave birth in April or May of 2020 were eligible for inclusion. Women were invited to take part via a hospital-based gatekeeper who had no other involvement in the study. FINDINGS: Nineteen women consented to take part and were interviewed. Four dominant themes reflective of women's views and experiences emerged during data analysis. These were: 'navigating the system', 'at the end of the day it's just you', 'preparing for and adapting to uncertainty' and 'blessing in disguise'. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Women experienced added challenges as a result of COVID-19 associated altered care structures and processes. Some changes implemented in response to the pandemic were positively experienced by women. The findings will contribute to and assist in planning future services for women and their partners, and in tailoring care to meet women's expectations and needs as the COVID-19 pandemic continues and beyond.