Experience-based Investigation and Co-design of Psychosis Centred Integrated Care Services for Ethnically Diverse People with Multimorbidity (CoPICS): study protocol.

INTRODUCTION: Ethnic minorities (also called racialised groups) are more likely to experience severe mental illness (SMI). People with SMI are more likely to experience multimorbidity (MM), making psychosis among racialised groups more likely to lead to MM, poor outcomes, disability and premature mortality. METHODS AND ANALYSIS: This National Institute for Health and Care Research-funded study (151887) seeks to use innovative participatory methods including photovoice and biographical narrative interviews in urban and rural areas of England to assemble experience data. These data will be subjected to polytextual thematic analysis, and alongside pictures and captions, will inform an experienced-based co-design of interventions, the implementation of which will be evaluated. There will be an economic analysis and a process evaluation of the implementation. ETHICS AND DISSEMINATION: This programme of work has received ethical (IRAS 322421; Newcastle North Tyneside Research Ethics Committee 23/NE/0143) and sponsor approval. The findings will be disseminated in galleries showing the creative work, as lay and academic summaries and infographics; as practice briefings for practitioners, commissioners and policy makers; peer-reviewed publications. TRIAL REGISTRATION NUMBER: https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/649c08111c037d0027b17d17/.

Effects of Dichlorodiphenyltrichloroethane on the Female Reproductive Tract Leading to Infertility and Cancer: Systematic Search and Review.

Persistent Organic Pollutants (POPs) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health issues, such as reduced fecundability; increased risk of preterm/premature deliveries; increased periods of gestation; alterations in the synthesis of crucial reproductive hormones (Progesterone and Oxytocin) through ion imbalances and changes in prostaglandin synthesis, myometrial and stromal hypertrophy, and edema; and variations in uterine contractions through increased uterine wet weight. There was also limited evidence indicating DDT as a carcinogen sufficient to instigate reproductive cancers. However, this review only takes into account the in vitro studies that have established a possible pathway to understand how DDT impacts female infertility and leads to reproductive cancers. Links between the pathways described in various studies have been developed in this review to produce a summarized picture of how one event might lead to another. Additionally, epidemiological studies that specifically targeted the exposure to DDT of females belonging to various ethnicities have been reviewed to develop an overall picture of prevailing female reproductive health concerns in different nations.

In-silico identification of small molecule benzofuran-1,2,3-triazole hybrids as potential inhibitors targeting EGFR in lung cancer via ligand-based pharmacophore modeling and molecular docking studies.

Lung cancer is one of the most common and deadly types of cancer worldwide, and the epidermal growth factor receptor (EGFR) has emerged as a promising therapeutic target for the treatment of this disease. In this study, we designed a library of 1840 benzofuran-1,2,3-triazole hybrids and conducted pharmacophore-based screening to identify potential EGFR inhibitors. The 20 identified compounds were further evaluated using molecular docking and molecular dynamics simulations to understand their binding interactions with the EGFR receptor. In-silico ADME and toxicity studies were also performed to assess their drug-likeness and safety profiles. The results of this study showed the benzofuran-1,2,3-triazole hybrids BENZ-0454, BENZ-0143, BENZ-1292, BENZ-0335, BENZ-0332, and BENZ-1070 dock score of - 10.2, - 10, - 9.9, - 9.8, - 9.7, - 9.6, while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of the receptor, indicating their potential as inhibitors. The in-silico ADME and toxicity studies suggested that the compounds had good pharmacokinetic and safety profiles, further supporting their potential as therapeutic agents. Finally, performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of benzofuran-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. Overall, this study provides a valuable starting point for the development of novel EGFR inhibitors with improved efficacy and safety profiles. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00157-1.

Pharmaceutical based cosmetic serums.

The growth and demand for cosmeceuticals (cosmetic products that have medicinal or drug-like benefits) have been enhanced for the last few decades. Lately, the newly invented dosage form, i.e., the pharmaceutical-based cosmetic serum has been developed and widely employed in various non-invasive cosmetic procedures. Many pharmaceutical-based cosmetic serums contain natural active components that claim to have a medical or drug-like effect on the skin, hair, and nails, including anti-aging, anti-wrinkle, anti-acne, hydrating, moisturizing, repairing, brightening and lightening skin, anti-hair fall, anti-fungal, and nail growth effect, etc. In comparison with other pharmaceutical-related cosmetic products (creams, gels, foams, and lotions, etc.), pharmaceutical-based cosmetic serums produce more rapid and incredible effects on the skin. This chapter provides detailed knowledge about the different marketed pharmaceutical-based cosmetic serums and their several types such as facial serums, hair serums, nail serums, under the eye serum, lip serum, hand, and foot serum, respectively. Moreover, some valuable procedures have also been discussed which provide prolong effects with desired results in the minimum duration of time after the few sessions of the serum treatment.

Integrated Care for Older People with Different Frailty Levels: A Qualitative Study of Local Implementation of a National Policy in Luton, England.

Introduction: The NHS England General Medical Services 2017-18 contract made it mandatory for general practices in England to identify and manage older people proactively. In response to the national policy, the Luton Framework for Frailty (LFF) programme was developed to target older residents of Luton and offer interventions according to their frailty level. The aim of this study was to gain a deeper understanding of the LFF and the factors that affect the implementation of a proactive integrated care service for older people with different frailty levels (OPDFL). Methods: We undertook document analyses and conducted semi-structured interviews with stakeholders to create a 'thick description' that provides insights into the LFF. Results: Healthy ageing interventions bring beneficial outcomes but to increase the uptake they should be co-produced with older people. A common electronic system within primary care and multidisciplinary team meetings (MDT) aid implementation. However, variation in implementation across Luton, different levels of buy-in for MDT, and different data systems in primary and secondary care make implementation challenging. Conclusion: The LFF is a promising initiative and lessons learned are likely to be transferable to other settings as proactive management of frailty takes on greater policy prominence in the UK and worldwide.

Acceptability and feasibility of screening pregnant women for sexually transmitted infections in Rawalpindi, Pakistan.

Objectives: To understand the acceptability and feasibility of sexually transmitted infection (STI) testing during antenatal care, along with the prevalence of STIs, in Rawalpindi, Pakistan. Methods: We enrolled pregnant women seeking antenatal care and performed STI testing using Cepheid GeneXpert® CT/NG and TV kits and Alere Determine™ HIV and syphilis tests. We used interviewer-administered surveys to collect medical, social, and sexual histories. Participants testing positive for STIs and their partners were treated. Results: We enrolled 1001 women from September to December 2019. Nearly all women offered to participate in this study enrolled. Most women understood the effects an STI can have on their pregnancy (99.6%) and valued STI screening during pregnancy (98.1%). 11 women tested positive for any STI: (Chlamydia trachomatis = 4, Neisseria gonorrhoeae = 1, and Trichomonas vaginalis = 6). Of those, six presented for a test-of-cure, and two were positive for Trichomonas vaginalis. None tested positive for HIV infection or syphilis (n = 503). Conclusions: STI testing during antenatal care in Rawalpindi was acceptable, valued, understood, and feasible. The prevalence of STIs in pregnant women was low. Continued prevalence monitoring is warranted.

Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding.

The Parkin co-regulated gene protein (PACRG) binds at the inner junction between doublet microtubules of the axoneme, a structure found in flagella and cilia. PACRG binds to the adaptor protein meiosis expressed gene 1 (MEIG1), but how they bind to microtubules is unknown. Here, we report the crystal structure of human PACRG in complex with MEIG1. PACRG adopts a helical repeat fold with a loop that interacts with MEIG1. Using the structure of the axonemal doublet microtubule from the protozoan Chlamydomonas reinhardtii and single-molecule fluorescence microscopy, we propose that PACRG binds to microtubules while simultaneously recruiting free tubulin to catalyze formation of the inner junction. We show that the homologous PACRG-like protein also mediates dual tubulin interactions but does not bind MEIG1. Our findings establish a framework to assess the function of the PACRG family of proteins and MEIG1 in regulating axoneme assembly.

Effectiveness of integrated chronic care interventions for older people with different frailty levels: a systematic review protocol.

INTRODUCTION: Frailty poses a huge burden to individuals, their families and to healthcare systems. Several interventions have been evaluated for the improvement of outcomes for older people with frailty, including integrated care interventions. Reviews synthesising evidence on the effectiveness of integrated care for older people with frailty have treated them as a single population, without considering the heterogeneity between different frailty levels such as non-frail, mild frailty, moderate frailty and severe frailty. Findings from these studies have shown inconsistent results on the various outcomes assessed. People with different frailty status have different care needs, which should be addressed accordingly. The aim of this study is to synthesise evidence on the effectiveness of integrated care interventions on older people with different frailty status who are community dwelling or living in retirement housing or residential setting but not in care homes or in nursing homes. METHODS AND ANALYSIS: This is a protocol for a systematic review assessing the effectiveness of integrated chronic care interventions on older people with different frailty status. A literature search will be conducted on the databases Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and clinical trial registers. Two authors will independently conduct search and screening for eligible studies. Full-text screening will be used to include only studies that fulfil the inclusion criteria. Data extraction will be done on a data extraction form and methodological quality of studies will be assessed using the Effective Practice and Organisation of Care risk of bias tool. The interventions will be described following Wagner's Chronic Care Model. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Institute for Health Research Ethics Committee of the University of Bedfordshire (IHREC934). The results of the review will be disseminated through a peer-reviewed journal article, conferences and also with local provider and user stakeholders. PROSPERO REGISTRATION NUMBER: CRD42020166908.

Effect and feasibility of district level scale up of maternal, newborn and child health interventions in Pakistan: a quasi-experimental study.

INTRODUCTION: Pakistan has a high burden of maternal, newborn and child morbidity and mortality. Several factors including weak scale-up of evidence-based interventions within the existing health system; lack of community awareness regarding health conditions; and poverty contribute to poor outcomes. Deaths and morbidity are largely preventable if a combination of community and facility-based interventions are rolled out at scale. METHODS AND ANALYSIS: Umeed-e-Nau (UeN) (New Hope) project aims is to improve maternal, newborn and child health (MNCH) in eight high-burden districts of Pakistan by scaling up of evidence-based interventions. The project will assess interventions focused on, first, improving the quality of MNCH care at primary level and secondary level. Second, interventions targeting demand generation such as community mobilisation, creating awareness of healthy practices and expanding coverage of outreach services will be evaluated. Third, we will also evaluate interventions targeting the improvement in quality of routine health information and promotion of use of the data for decision-making. Hypothesis of the project is that roll out of evidence-based interventions at scale will lead to at least 20% reduction in perinatal mortality and 30% decrease in diarrhoea and pneumonia case fatality in the target districts whereas two intervention groups will serve as internal controls. Monitoring and evaluation of the programme will be undertaken through conducting periodical population level surveys and quality of care assessments. Descriptive and multivariate analytical methods will be used for assessing the association between different factors, and difference in difference estimates will be used to assess the impact of the intervention on outcomes. ETHICS AND DISSEMINATION: The ethics approval was obtained from the Aga Khan University Ethics Review Committee. The findings of the project will be shared with relevant stakeholders and disseminated through open access peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: NCT04184544; Pre-results.

In vitro antifungal activity of 9, 10-dihydrophenanthrene-2-carboxylic acid isolated from a marine bacterium: Pseudomonas putida.

An antifungal compound 9, 10-dihydrophenanthrene - 2 - carboxylic acid was isolated from a marine derived bacterium Pseudomonas putida isolated from surface water samples of Karachi fish harbor coast line. The structure was explored using extensive 1D- and 2D-NMR spectroscopic techniques. The compound was found to be active against fungal strains obtained from clinical samples whereas strong activity was noted against Candida albicans with a MIC value of 20µg/ml, as the purified compound showed promising anticandidal activity a multidisciplinary approach is needed to explore further this compound as potential pharmacological lead compound against Candida spp and will add in the global hunt for clinically functional antifungal agents.

Takotsubo Cardiomyopathy Presenting with Sinoatrial Disease: A Rare Presentation.

Takotsubo cardiomyopathy (TCM), or apical ballooning syndrome, is a distinct nonischemic cardiomyopathy mimicking acute coronary syndrome. A 76-year-old female presented with ST elevation in the inferior lead and a troponin level of 0.81 ng/dL. An immediate coronary angiography showed non-obstructive coronary artery disease. A subsequent ventriculogram and echocardiogram showed anteroapical and distal inferior wall hypokinesis suggestive of TCM. Despite therapy with beta blocker, she was observed to have two significant sinus pauses, one eight-second, and a second 29-second pause. An urgent transvenous pacemaker was put in place and later followed by a permanent pacemaker. The patient was discharged on carvedilol and losartan. Although other arrhythmias such as complete heart block, torsades, and ventricular arrhythmias have been commonly reported, the association of TCM with recurrent sinus arrest has rarely been reported in the literature. The occurrence observed in this case implies that patients with TCM should be monitored closely for arrhythmias, and, if such a condition is identified, planning for permanent pacemaker implantation should be started early enough to avoid recurrent life-threatening episodes.

The Disappearing Murmur: Systolic Anterior Motion of the Mitral Valve Leaflet in a Non-hypertrophic Cardiomyopathy Patient.

Systolic anterior motion (SAM) of the mitral valve is a well-known phenomenon associated with left ventricular outflow tract obstruction and hemodynamic compromise. This finding may occur in patients with or without hypertrophic cardiomyopathy. In this report, a patient with no prior medical history presented to the hospital with left-sided chest pain and high-risk echocardiogram (ECG) findings. Left heart catheterization with coronary angiography was negative for coronary artery disease. His initial examination was significant for a systolic murmur due to the underlying SAM, as demonstrated by transthoracic echocardiogram. During his hospitalization, he developed acute heart failure syndrome as a result of dynamic outflow tract obstruction. He was treated with fluid resuscitation with a resolution of his hemodynamic compromise. On a follow-up examination, there was no murmur and SAM was no longer present on echocardiogram. This case demonstrates the importance of recognizing the clinical manifestations of SAM as well as its role in maintaining an appropriate hemodynamic status.

A Reversible Cause of Complete Heart Block Causing Chest Pain and Syncope.

Vasospastic angina (VSA), also known as variant or Prinzmetal's angina, is a relatively uncommon cause of retrosternal chest pain with transient ST segment elevation, mainly due to vasospasm in the coronary arteries. This is a case of 37-year-old female who presented with chest pain and syncope. Her initial workup, including echocardiogram, was negative. Subsequently, she was sent home with an event monitor. During the next two weeks, she continued to have recurrent episodes of similar chest pains and presented to her cardiology appointment with a heart rate of 45 bpm and blood pressure of 100/60 mmHg and was taken to hospital emergency department. Event monitor review showed intermittent complete heart block. In the hospital, the electrocardiogram (EKG) showed complete heart block and inferior lead ST elevations concomitantly with the chest pains. Although suspicious for vasospastic angina, coronary artery disease had to be ruled out for which patient underwent coronary angiography without evidence of significant obstructive disease. Immediately thereafter, the patient underwent permanent pacemaker placement without recurrence of syncopal episodes. This case signifies complete heart block as one of the rare complications of vasospastic angina which otherwise can also lead to symptoms such as dizziness, shortness of breath, syncope, cardiac arrest, and sudden cardiac death.