bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying bacterial efflux within subcellular domains of
Pseudomonas aeruginosa
Authors: Li Yujie , Wilhelm Michael J. , Wu Tong , Hu Xiao-Hua , Ruiz Oscar N. , Dai Hai-Lung
Published: October 2024

Molecular efflux is a mechanism through which bacteria actively expel undesirable substances. This is a crucial line of defense against toxic chemicals in harsh environments. Understanding how efflux works is critical for designing antimicrobial strategies. Though much is already known about efflux proteins, important details about the mechanisms of efflux (e.g., importance of specific subcellular domains and ejection rates) have yet to be experimentally quantified. Herein, we use the nonlinear optical technique, second harmonic light scattering, to simultaneously measure the efflux rates from the periplasm and cytosol of a Gram-negative bacterium. The influence of efflux on the uptake kinetics of a mild antimicrobial, malachite green (MG), by
Pseudomonas aeruginosa
was quantified. It is observed that efflux primarily occurs from the periplasm and is two orders of magnitude faster than from the cytosol. Efflux pumps activate to maintain MG concentrations in the periplasm below 1 µM, while efflux from the cytosol maintains MG concentration below 0.1 µM. Efflux pumps are shown to saturate when exogenous MG concentrations are greater than 25 µM, while the cytosol efflux function saturates at >15 µM. Finally, efflux pumps can simultaneously eject different compounds, as proven by experiments with both MG and hexane, a known effluxable compound.

IMPORTANCE

Molecular efflux pumps are a crucial defense mechanism that protects bacteria from an otherwise unchecked influx of toxic molecules present in the extracellular environment. The efflux functions constitute a significant hindrance to antimicrobial efficacy. While much is now known regarding the structure of these channels, knowledge of the influence of efflux in individual subcellular domains and the associated ejection rates is still lacking. Using the nonlinear optical technique, second-harmonic light scattering, we have measured the threshold concentrations for pump activation, saturation concentrations, and efflux rates from both the periplasm and cytosol in living Gram-negative bacteria. The quantified efflux data in the different subcellular compartments not only provide a clear mechanistic understanding but also are critical for developing antimicrobial strategies.
Genomic characterization of a clonal emergent
Salmonella
Minnesota lineage in Brazil reveals the presence of a novel megaplasmid of resistance and virulence
Authors: dos Santos Anamaria M. P. , Panzenhagen Pedro , Ferrari Rafaela G. , Portes Ana Beatriz , de Jesus Ana Carolina , Ochioni Alan , Rodrigues Dália , Toro Magaly , Meng Jianghong , Allard Marc , Conte-Junior Carlos A.
Published: October 2024

Salmonella
Minnesota has emerged in Brazil as the predominant serovar in poultry and poultry products, along with
Salmonella
Heidelberg. To understand the emergence of
Salmonella
Minnesota over the last few years in Brazil, we performed a comparative analysis between 69 selected
S
. Minnesota genomes from Pathogen Detection database and 65 clonal emergent genomes isolated from Brazil. We demonstrate the presence of multidrug resistance genes against tetracycline [
tet
(A)], sulfonamide (
sul2
), and AmpC beta-lactamase (
bla
CMY-2
) in emergent genomes, along with the carriage of a megaplasmid of resistance and virulence (~210 kb), designated pESM (plasmid for emergent
Salmonella
Minnesota). pESM is an IncC/A2 plasmid predicted to increase
S
. Minnesota environmental tolerance to mercury (
mer
operon) and provide resistance to tetracycline and ampicillin due to the presence of
tet
(A) and
bla
CMY-2
, respectively. Moreover, pESM carries the yersiniabactin siderophore (high-pathogenicity island of
Yersinia
) related to the iron uptake. The temporal inference demonstrated that the most recent common ancestor dated from ~1978 and that the clonal emergent genomes carrying the pESM belong to a completely different lineage of
S
. Minnesota. Our results indicate that the presence of pESM likely contributes to the emergence of
S
. Minnesota and is precisely related to the successful spread of this particular clonal lineage in Brazil.

IMPORTANCE

Salmonella
Minnesota has emerged in Brazil as one of the leading serovars related to human and animal infection, presenting high virulence and antibiotic resistance to drugs classified as the highest priority for clinical treatment in humans. This study performed whole-genome sequencing, temporal analysis, and phylogenetics to understand the genetic insights related to the emergence of
Salmonella
Minnesota in Brazil. Long-read sequencing has led to the identification and characterization of a unique megaplasmid carrying virulence, antibiotic resistance, and heavy-metal tolerance genes, which may play a central role in
S
. Minnesota’s successful emergence in Brazil and possibly worldwide. The potentially high transmissibility of this plasmid between clones and serovars represents a risk to public health since its acquisition may increase
Salmonella
’s fitness, virulence, resistance, and persistence. Understanding the genetic aspects related to the emergence of serovars can help devise measures to mitigate the spread of hazardous multidrug-resistant strains.
The efflux system CdfX exports zinc that cannot be transported by ZntA in
Cupriavidus metallidurans
Authors: Schulz Vladislava , Galea Diana , Schleuder Grit , Strohmeyer Philipp , Große Cornelia , Herzberg Martin , Nies Dietrich H.
Published: October 2024

Cupriavidus metallidurans
is able to survive exposure to high concentrations of transition metals, but is also able to grow under metal starvation conditions. A prerequisite of cellular zinc homeostasis is a flow equilibrium combining zinc uptake and efflux processes. The mutant strain ∆e4 of the parental plasmid-free strain AE104 with a deletion of all four chromosomally encoded genes of previously known efflux systems ZntA, CadA, DmeF, and FieF was still able to efflux zinc in a pulse-chase experiment, indicating the existence of a fifth efflux system. The gene
cdfX
, encoding a protein of the cation diffusion facilitator (CDF) family, is located in proximity to the
cadA
gene, encoding a P-type ATPase. Deletion of
cdfX
in the ∆e4 mutant resulted in a further decrease in zinc resistance. Pulse-chase experiments with radioactive
65
Zn(II) and stable-isotope-enriched
67
Zn(II) provided evidence that CdfX was responsible for the residual zinc efflux activity of the mutant strain ∆e4. Reporter gene fusions with
cdfX-lacZ
indicated that the MerR-type regulator ZntR, the main regulator of
zntA
expression, was responsible for zinc- and cadmium-dependent upregulation of
cdfX
expression, especially in mutant cells lacking one or both of the previously characterized efflux systems, ZntA and CadA. Expression of
zntR
also proved to be controlled by ZntR itself as well as by zinc and cadmium availability. These data indicate that the
cdfX-cadA
region provides
C. metallidurans
with a backup system for the zinc-cadmium-exporting P-type ATPase ZntA, with CdfX exporting zinc and CadA cadmium.

IMPORTANCE

Bacteria have evolved the ability to supply the important trace element zinc to zinc-dependent proteins, despite external zinc concentrations varying over a wide range. Zinc homeostasis can be understood as adaptive layering of homeostatic systems, allowing coverage from extreme starvation to extreme resistance. Central to zinc homeostasis is a flow equilibrium of zinc comprising uptake and efflux reactions, which adjusts the cytoplasmic zinc content. This report describes what happens when an imbalance in zinc and cadmium concentrations impairs the central inner-membrane zinc efflux system for zinc by competitive inhibition for this exporter. The problem is solved by activation of Cd-exporting CadA or Zn-exporting CdfX as additional efflux systems.
Detection of
Hepatovirus A
(HAV) in wastewater indicates widespread national distribution and association with socioeconomic indicators of vulnerability
Authors: Zulli Alessandro , Chan Elana M. G. , Boehm Alexandria B.
Published: October 2024

Wastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding the occurrence of hepatitis A infections in communities. In this study, we measured concentrations of
Hepatovirus A
(HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,079 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both
P
< 0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both
P
< 0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.

IMPORTANCE

Despite the existence of a highly effective vaccine for hepatitis A, outbreaks in vulnerable populations remain common. The disease can be asymptomatic or subclinical, and disproportionately impacts populations with inadequate access to healthcare, leading to a severe underestimation of the occurrence of this viral infection. This study investigates the potential for wastewater measurements of biomarkers of the causative agent of hepatitis A (HAV RNA) to provide insights into disease occurrence. Results highlight the potential for wastewater-based epidemiology to be a complementary tool to traditional surveillance for monitoring and controlling HAV transmission.
Effects of global change drivers on the expression of pathogenicity and stress genes in dryland soil fungi
Authors: Romero-Olivares Adriana L. , Lopez Andrea , Catalan-Dibene Jovani , Ferrenberg Scott , Jordan Samuel E. , Osborne Brooke
Published: October 2024

The impacts of global climate change on dryland fungi have been understudied even though fungi are extremely sensitive to changes in the environment. Considering that many fungi are pathogens of plants and animals, including humans, their responses to anthropogenic change could have important implications for public health and food security. In this study, we investigated the potential physiological responses (i.e., metatranscriptomics) of pathogenicity and stress in dryland fungi exposed to global change drivers, drought, and the physical disturbance associated with land use. Specifically, we wanted to assess if there was an increase in the transcription of genes associated to pathogenicity and stress in response to global change drivers. In addition, we wanted to investigate which pathogenicity and stress genes were consistently differentially expressed under the different global change conditions across the heterogeneous landscape (i.e., microsite) of the Chihuahuan desert. We observed increased transcription of pathogenicity and stress genes, with specific genes being most upregulated in response to global change drivers. Additionally, climatic conditions linked to different microsites, such as those found under patches of vegetation, may play a significant role. We provide evidence supporting the idea that environmental stress caused by global change could contribute to an increase of pathogenicity as global climate changes. Specifically, increases in the transcription of stress and virulence genes, coupled with variations in gene expression, could lead to the onset of pathogenicity. Our work underscores the importance of studying dryland fungi exposed to global climate change and increases in existing fungal pathogens, as well as the emergence of new fungal pathogens, and consequences to public health and food security.

IMPORTANCE

The effects of global climate change on dryland fungi and consequences to our society have been understudied despite evidence showing that pathogenic fungi increase in abundance under global climate change. Moreover, there is a growing concern that global climate change will contribute to the emergence of new fungal pathogens. Yet, we do not understand what mechanisms might be driving this increase in virulence and the onset of pathogenicity. In this study, we investigate how fungi respond to global change drivers, physical disturbance, and drought, in a dryland ecosystem in terms of pathogenicity and stress. We find that indeed, under global change drivers, there is an increase in the transcription and expression of genes associated to pathogenicity and stress, but that microclimatic conditions matter. Our study shows the importance of investigating dryland fungi exposed to global climate change and impacts on our society, which may include threats to public health and food security.
Unraveling the role of cAMP signaling in
Giardia
: insights into PKA-mediated regulation of encystation and subcellular interactions
Authors: Shih Han-Wei , Alas Germain C. M. , Paredez Alexander R.
Published: October 2024

cAMP plays an important role as a second messenger in the stage transition of various protozoan parasites. This signaling pathway relies on multiple effectors, such as protein kinase A (PKA), exchange protein activated by cAMP, and cAMP-response element binding protein transcription factors, to initiate signal transduction in humans. The
Giardia
genome only contains two adenylate cyclases (ACs), a single phosphodiesterase (PDE) and a single known PKA effector, and the specific functions of these components are not fully understood. In our previous research, we demonstrated the important role of AC2-dependent cAMP signaling in promoting the encystation program. Using the NanoBit technology, we emphasized the significance of AC2-dependent cAMP biosynthesis in regulating the dissociation of the PKA regulatory domain (PKAr) and PKA catalytic domain (PKAc). In this study, our objectives are twofold: first, we used the newly developed Split-Halo to examine subcellular interactions of
Gl
PKAr and
Gl
PKAc in
Giardia
; and second, we investigated whether PKAc regulates encystation-specific proteins. Our findings revealed distinct subcellular locations where
Gl
PKAr and
Gl
PKAc interacted during the trophozoite stage, including the flagella, basal bodies, and cytoplasm. Upon exposure to encystation stimuli, the interaction shifted from the flagella to the cytosol. Knockdown of
Gl
PKAc resulted in the downregulation of encystation-specific genes, leading to the production of fewer viable and water-resistant cysts indicating a role for PKA in the transcriptional regulation of encystation. These discoveries contribute to a deeper understanding of the cAMP signaling pathway and its important role in governing
Giardia
’s encystation process.

IMPORTANCE

The precise timing of interactions and subcellular compartmentation play crucial roles in signal transduction. The co-immunoprecipitation assay (CO-IP) has long been utilized to validate protein–protein interactions; however, CO-IPs lack spatial and temporal resolutions. Our recent study used the NanoBit assay, which showcased the reversible protein–protein interaction between PKAr and PKAc in response to cAMP analogs and encystation stimuli. Expanding on this groundwork, this study employs the Split-Halo assay to uncover the subcellular compartments where the PKAr and PKAc protein–protein interactions take place and respond to encystation stimuli. Taken together, these molecular tools provide spatiotemporal information on the protein–protein interaction, which will be useful in the field.
Effect of combined probiotics and doxycycline therapy on the gut–skin axis in rosacea
Authors: Yu Jie , Duan Yan , Zhang Meng , Li Qi , Cao Miao , Song Weixin , Zhao Feiyan , Kwok Lai-Yu , Zhang Heping , Li Ruiya , Sun Zhihong
Published: October 2024

Rosacea is a chronic inflammatory skin condition marked by facial erythema, telangiectasia, and acne-like eruptions, affecting millions worldwide. While antibiotics remain a common treatment, prolonged use has significant adverse effects and can lead to antibiotic resistance. This study evaluated the impact of combined probiotics and doxycycline treatment on rosacea, emphasizing the gut–skin axis. Sixty rosacea patients were randomly assigned to the probiotic, placebo, or control groups. After a 2-week doxycycline treatment, participants underwent a 3-month intervention with either a placebo, probiotic, or no further treatment. Clinical outcomes were assessed at baseline and after the 14-week intervention. Our results showed that probiotic administration improved facial skin conditions, alleviated inflammation, and reduced facial skin microbiota diversity while enhancing gut microbiota heterogeneity. Multivariate analysis identified microbial markers distinguishing the probiotic group from the control and placebo groups, and some markers were associated with skin health parameters. After the probiotic intervention, some facial skin-associated taxa, such as
Aquabacterium
sp.,
UBA4096
sp. 1,
UBA4096
sp. 2, and
Yimella indica
, decreased in abundance. Additionally, the fecal microbiota of the probiotic group was enriched in specific gut microbes, including
Streptococcus parasanguinis
,
Erysipelatoclostridium ramosum
, and
Coprobacillus cateniformis
, while showing a reduced abundance of
Bacteroides vulgatus
. These changes were associated with reduced facial sebum levels and a lower physician’s global assessment score. Finally, fewer antibiotic resistance genes, particularly tetracycline resistance genes, were detected in the probiotic group compared with the control and placebo groups. Our study supports the existence of a gut–skin axis and the application of probiotics in managing rosacea.

IMPORTANCE

This research elucidates rosacea management with novel insights into probiotic use alongside doxycycline, showing dual benefits in symptom relief and inflammation reduction in patients. The study maps probiotic-induced shifts in gut and skin microbiota, underscoring microbial shifts correlating with skin health improvements. Crucially, it deciphers the gut–skin axis modulation by probiotics, proposing a method to curb antibiotic resistance in rosacea therapies. This study furnishes robust evidence for probiotics in rosacea, advancing our grasp of the gut–skin relationship.
Translithospheric carbonatite magmatic system of the world’s largest REE deposit, Bayan Obo, China
Authors: Xue Guoqiang , Zhang Ji’en , Chen Weiying , Wu Xin , Wang Jian , Di Qingyun , Xu Ya , Zhao Yonggang , Li Xianhua , Zhao Yulong , Mitchell Ross
Published: October 2024

Critical rare earth elements (REEs) are often sourced from carbonatite worldwide. In some cases, the magmatic system at depth is not well depicted due to a lack of geophysical constraints. The world’s largest REE deposit, Bayan Obo of the North China craton, offers a template for tracing such a system using 2-D electrical resistivity imaging. We first restore modifications triggered by two newly discovered Mesozoic thrust faults. The thrust fault along Boluotou, Dongjielegele, and south West Pit displaced gneiss and the carbonatite, which was intruded by Permian granite, in the hanging wall from Kulue ~30 km south of Bayan Obo, as evidenced by four similar left-step en echelon high aeromagnetic anomalies. The second Haoqin–North Jianshan fault thrust is another carbonatite at Boluotou, East-Main-West pits, and Dongjielegele and Paleoproterozoic metasediments over Paleozoic sediments, that correlate with the Shuiyuantou klippe to constrain a displacement of ~14 km. After restoration, both carbonatites are revealed to be situated above two low resistivity zones. We propose a Mesoproterozoic translithospheric carbonatite magmatic system consisting of a frozen zone of partial melt and mantle sill complexes stemming from as deep as near the lithosphere–asthenosphere boundary at 60–70 km depth and two magma pathways, plumbing magma upward across the crust to generate two carbonatites with multiple branches at the surface. Our geophysical constraint on the magmatic system of this giant REE deposit can serve as a blueprint for understanding and exploring other existing and new REE deposits.
Bronchopulmonary sequestration presenting as haemoptysis with an aberrant blood supply from the pulmonary artery
Authors: Hussain Kashmala , Suleman Sahar , Fatimi Saulat Husnain , Khan Javaid Ahmed
Published: October 2024

Bronchopulmonary sequestration is a rare condition characterised by the presence of nonfunctional, dysplastic lung tissue. This tissue receives blood supply from the systemic circulation. In this case report, we document an exceptional presentation of a woman in her 50s where bronchopulmonary sequestration in the right upper lung lobe led to haemoptysis. This sequestration received blood supply from a pulmonary artery branch, which is unusual and contrary to the usual systemic circulation. The patient underwent a right upper lobectomy, which confirmed the diagnosis of pulmonary sequestration on histopathology. The unique vascular supply and location of this case challenge conventional diagnostic and management approaches. It emphasises the necessity for meticulous evaluation and consideration of alternative vascular sources in bronchopulmonary sequestration cases.
Association between physical activity and immunosuppressive medication adherence among renal transplant recipients: a case–control study
Authors: Zhang Pengpeng , Fan Xiaofei , Xiang Linghui , Zhu Xiao , Liu Dian , Liu Jia
Published: October 2024

Background

Behavioural interventions are closely associated with immunosuppressive medication (IM) adherence. We aimed to explore the relationship between physical activity and IM adherence among renal transplant patients (RTPs) to determine potential interventions to improve IM adherence.

Design

A case–control study.

Setting

Single-centre study in Changsha, China.

Participants

The study population included 624 RTPs who were adherent to IM and 417 RTPs who were non-adherent to IM.

Main outcome measures

Sociodemographic characteristics of RTPs, IM adherence and the association between physical activity patterns or frequency and IM adherence.

Results

The proportion of RTPs who were non-adherent to IM was 40.06%. Compared with RTPs non-adherent to IM, those who were adherent were older, more likely to be married, were evaluated closer to initial time of transplant, had shorter pretransplant waiting times and engaged in more physical activity. Multivariate logistic regression analysis showed that, in the pretransplant stage, only high-frequency aerobic physical activity was significantly associated with IM adherence. However, in the post-transplant stage, patients engaging in low-frequency aerobic physical activity, high-frequency resistance physical activity or high-frequency aerobic physical activity had 2.01, 2.96 and 2.67 times greater odds of being adherent to IM, respectively, compared with patients with no physical activity. RTPs without physical activity in the pretransplant stage were more likely to be adherent to IM if they engaged in post-transplant physical activity. RTPs engaging in low-frequency physical activity in the pretransplant stage may have better IM adherence if they engaged in post-transplant physical activity. RTPs engaging in high-frequency post-transplant physical activity were significantly associated with a greater likelihood of being adherent to IM compared with RTPs engaging in low-frequency post-transplant physical activity.

Conclusion

Our study revealed that physical activity, especially in the post-transplant stage, is closely associated with IM adherence and presents a potential intervention for improving IM adherence by RTPs.
Clinical practice guidelines for person-centred handover practices in emergency departments: a scoping review
Authors: de Lange Santel , Heyns Tanya , Filmalter Celia
Published: October 2024

Objective

To review the available information on clinical practice guidelines for person-centred and current handover practices between emergency care practitioners (ECPs) and healthcare professionals in emergency departments (EDs). Collating existing clinical practice guidelines may improve handover practices.

Eligibility criteria

Clinical practice guidelines for person-centred handover practices between ECPs and healthcare professionals in EDs. ECPs transporting and handing patients over to healthcare professionals in EDs. Healthcare professionals including doctors and nurses working in EDs, who are involved in handovers with ECPs. Studies conducted in EDs, emergency rooms or emergency centres in any geographical area. No language or time restrictions were applied. The search included published and unpublished studies, opinion papers as well as primary sources, and evidence synthesis. All qualitative and quantitative research designs were included.

Sources of evidence

The literature on clinical practice guidelines for person-centred handover practices was reviewed. Three electronic databases were searched: MEDLINE (PubMed), CINAHL (EBSCO) and Scopus from inception to May 2023 with no time limits set for the inclusion of published literature in the review. Six guideline organisations were also searched.

Charting methods

A data extraction tool was developed, pilot-tested and used to extract data from the included studies.

Results

19 studies met the inclusion criteria. Various mnemonics exist for handover practices. Where mnemonics are not used, participants have identified important information that should be included during handover practices. We did not find any clinical practice guidelines or information on person-centred handover practices in any of the reviewed articles.

Conclusions

Currently, there is no gold standard for person-centred handover practices, which has led to various practices being implemented. Currently, there is a paucity of literature on person-centred handover practices. Most articles expressed a need for standardised handover practices; however, not all aspects of handover practices can be standardised and should be kept patient and context-specific.

Trial and protocol registration

This scoping review protocol was registered on Figshare (10.6084/m9 /m9.figshare.21731528).
Assessment of the productivity loss due to leading maternal ill-health conditions: a follow-up study of a prospective pregnancy cohort in rural Sri Lanka
Authors: Gunarathna Sajan Praveena , Wickramasinghe Nuwan Darshana , Agampodi Thilini Chanchala , Prasanna Indika Ruwan , Agampodi Suneth Buddhika
Published: October 2024

Objectives

This study aimed to assess the productivity loss and cost due to maternal ill-health conditions and its associated factors throughout pregnancy in rural Sri Lanka.

Design

A follow-up study of women registered in the Rajarata Pregnancy Cohort (RaPCo).

Setting

Anuradhapura district, Sri Lanka.

Participants

1573 pregnant women who were followed up from pregnancy identification to termination.

Primary and secondary outcome measures

The primary outcome measures of this study are productivity loss due to maternal ill-health conditions expressed by days/month and productivity cost due to maternal ill-health conditions expressed in monetary terms (US$)/month. Data were collected monthly, and all pregnant women were asked to report the leading cause of maternal ill-health condition and the associated loss due to absenteeism and presenteeism.

Results

During the pregnancy follow-up, 3595 (81.5%) months had at least one episode of maternal ill-health condition. Of these, only 1729 (48.1%) episodes sought medical care. Assistance for lost routine work was reported in 1281 (35.6%) episodes. The absenteeism, presenteeism and gross and net productivity loss per month were 3.6, 4.5, 8.1 and 5.5 days/month, respectively. The corresponding productivity cost was US$15.26/month. Nausea and vomiting (NVP) reported the highest prevalence (n=1599, 44.5%) until the second month of the third trimester, presenteeism (5.5 days/month) and gross productivity loss (9.5 days/month). Pregnant women with vaginal bleeding reported the highest absenteeism (6.2 days/month) and net productivity loss (6.8 days/month). Pregnant women diagnosed with anaemia reported the highest productivity cost (US$26.98/month). Monthly household expenditure, poverty and receiving assistance were the associated factors of productivity loss (p<0.05).

Conclusion

Maternal ill-health conditions during pregnancy lead to productivity loss in rural Sri Lanka. NVP, vaginal bleeding and anaemia are the leading causes of productivity loss. Hence, controlling and preventing the leading causes are the recommended priorities.
Efficacy of problem-solving therapy in treating late-life depression with potential cognitive impairment: a systematic review and meta-analysis
Authors: Huang Chun , Fang Yuan , Yan Feng , Wang Tao , Cai Dongbin , Zhang Zhiling , Li Xia , Wang JianJun
Published: October 2024

Introduction

Late-life depression (LLD) is a global public health issue, often accompanied by cognitive impairments that can exacerbate the severity of depression and impair social functioning. Despite being a well-established treatment for LLD, the suitability of problem-solving therapy (PST) for individuals with LLD and varying degrees of cognitive impairments warrants further investigation. This paper presents the protocol for a systematic review and meta-analysis of randomised controlled trials (RCTs) aimed at evaluating the effectiveness and acceptability of PST for this specific demographic.

Methods/analysis

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we will conduct a systematic review to synthesise existing research on PST for individuals in this demographic. We will comprehensively search multiple databases and sources, including PubMed, EMBASE, the Cochrane Database and APA PsycNET from inception to October 2023, without language, publication year or type restrictions. Relevant studies will be manually screened from the references. Only RCTs involving PST for LLD will be included. The primary efficacy outcome will be the standardised mean difference in total scores on continuous depression severity scales across different comparison arms. Data extraction will be conducted independently by two reviewers (CH and J-JW), and methodological rigour will be assessed using the Cochrane Risk of Bias assessment tool. Subgroup and sensitivity analyses will be performed to investigate the impact of concomitant cognitive impairments and to evaluate the robustness of the findings.

Ethics and dissemination

The meta-analysis project is expected to be ethically unproblematic and does not require approval from a research ethics committee. The results of this study will be shared through articles in scholarly peer-reviewed journals and presentations in various formats, both print and digital.

PROSPERO registration number

CRD42023473782
Protocol for a community-based, household-randomised, dose–response trial to assess the acceptability, nutritional effects and safety of double-fortified salt containing iodine and folic acid compared with iodised salt among non-pregnant Ethiopian women of reproductive age (DFS-IoFA)
Authors: Brown Kenneth H , Tessema Masresha , McDonald Christine M , Agbemafle Isaac , Woldeyohannes Meseret , Fereja Mengistu , Nane Debritu , Arnold Charles D , Waka Feyissa Challa , Tesfaye Biniyam , Arabi Mandana , Martinez Homero
Published: October 2024

Introduction

The prevalence of neural tube defects (NTDs) is higher in Ethiopia than most other countries, and ~84% of Ethiopian women of reproductive age (WRA) have folate insufficiency, a major risk factor for NTDs. Salt fortification with folic acid is a potential strategy to improve women’s folate status, but data are needed on the acceptability, nutritional impact and safety of folic acid fortification of iodised salt.

Methods and analysis

The study is designed as a community-based, household-randomised, dose–response trial. A total of 360 non-pregnant WRA 18–49 years of age will be randomly assigned to one of three intervention arms: (1) iodised salt fortified with 30 ppm folic acid to provide ~200 µg folic acid/day; (2) iodised salt fortified with 90 ppm folic acid to provide ~600 µg folic acid/day; or (3) iodised salt (comparator). The preweighed salts will be delivered to participants’ homes biweekly for 26 weeks; unused salt will be collected and weighed. Fasting, venous blood samples will be collected at baseline, end line and a randomly assigned intermediate time point for assessment of folate, iodine, vitamin B12and other micronutrient status biomarkers. Women’s dietary intakes, including discretionary salt consumption, will be measured using weighed food records; 24-hour urine specimens will be analysed for sodium and iodine excretion. Primary outcomes are women’s consumption of study salts, change in biomarkers of folate and iodine status and prevalence of adverse events. Results will be analysed using analysis of covariance models to estimate group mean differences for continuous outcomes, controlling for baseline measurements, and log-binomial or modified Poisson regressions for categorical outcomes. Prespecified effect modifications will be explored.

Ethics and dissemination

The study has been approved by the Ethiopian Public Health Institute’s Institutional Review Board, and the protocol has been registered with ClinicalTrials.gov (registration numberNCT06223854). Study results will be published in open access scientific journals and disseminated nationally in Ethiopia.

Trial registration number

NCT06223854.
Antifungal combinations in paediatric invasive fungal infections: a protocol for systematic review and meta-analysis
Authors: Ramadhan Roy Novri , Rampengan Derren David Christian Homenta , Gunawan Felicia Angelica , Kadariswantiningsih Ika N , Empitu Maulana
Published: October 2024

Background

Invasive fungal infections (IFIs) significantly impact immunocompromised paediatric patients, contributing to high rates of morbidity and mortality. Despite the evolution of antifungal therapy, the efficacy and safety of combination antifungal therapies in paediatric patients, especially those with haematological malignancies, remain controversial. This systematic review and meta-analysis seeks to critically evaluate the efficacy and safety of antifungal combinations in paediatric IFIs.

Methods

We will conduct a search in PubMed, ScienceDirect, Cochrane Library, BMJ and Springer databases to include randomised controlled trials and observational studies focused on combination antifungal therapies in paediatric patients under 18 years with IFIs, using COVIDENCE for data management and analysis, ensuring rigorous quality assessment and statistical integrity in synthesising data. The time frame for the search will encompass publications from the inception of each database to the present, ensuring a comprehensive coverage of the literature. The database search will not be restricted by date. The review will assess combined antifungal treatment against placebo or single-antifungal therapy, examining outcomes like response rates, survival, mortality, adverse effects, cost-effectiveness and quality of life.

Ethics and dissemination

The review will be disseminated to healthcare professionals, community groups and policy-makers via journal publication and conference presentations to help them tailor antifungal prophylaxis treatment and outcomes for paediatric patients with IFIs. The analysis will not include any individual patient data, so ethical approval is not required.

PROSPERO registration number

CRD42024503620.
Prevalence and risk factors of primary dysmenorrhoea among medical students: a cross-sectional survey in Indonesia
Authors: Situmorang Herbert , Sutanto Reynardi Larope , Tjoa Kevin , Rivaldo Rivaldo , Adrian Michael
Published: October 2024

Objectives

This study aimed to assess the prevalence and associated risk factors of primary dysmenorrhoea among medical students in Indonesia.

Design

A web-based survey was conducted among 630 medical students across Indonesia, selected based on specific inclusion criteria. Dysmenorrhoea prevalence, severity and associated risk factors were assessed using a self-reported questionnaire. To analyse the data, univariate and multiple binary logistic regression analyses were performed. A significance level of 5% (p<0.05) was used for both types of analyses to determine the statistical significance of the observed associations.

Setting and participants

Indonesia (2021: n=630 female medical students).

Outcomes

The primary outcome is primary dysmenorrhoea, defined as painful menses without previous diagnosis of pelvic pathology. The severity of dysmenorrhoea was measured using the Verbal Multidimensional Scoring System. Independent variables include socio-demographic characteristics, menstrual history and other identified associated risk factors.

Results

Of the 630 Indonesian medical students surveyed, a large proportion (91.27%) reported experiencing dysmenorrhoea, with 52.35% experiencing moderate-to-severe pain. Family history of dysmenorrhoea emerged as a significant predictor for both occurrence (OR 3.76; 95% CI 1.89 to 7.45) and severity (OR 1.47; 95% CI 1.04 to 2.06). Dysmenorrhoea severity was positively associated with cycle length (OR 1.57; 95% CI 1.01 to 2.43), whereas higher body mass index (BMI) (OR 0.94; 95% CI 0.90 to 0.98) and being Indonesian of foreign descent (OR 0.46; 95% CI 0.27 to 0.84) were negatively associated with moderate-to-severe dysmenorrhoea.

Conclusions

Dysmenorrhoea is prevalent among Indonesian medical students, with family history, BMI, cycle length and race significantly associated with its occurrence or severity. These findings underscore the need for further research on more diverse populations to enhance awareness and address this prevalent gynaecological concern effectively.
Impact of awake extracorporeal membrane oxygenation on patients mortality with cardiogenic shock: a systematic review and trial sequential meta-analysis based on observational studies
Authors: Yue Han-yang , Peng Wei , Luo Kun , Zeng Jun , Ma Wei , Lu Charles Damien , Chang Li , Jiang Hua , Zhou Ping
Published: October 2024

Objectives

The use of awake extracorporeal membrane oxygenation (ECMO, without intubation or sedation under ECMO support in patients with cardiogenic shock is growing rapidly because emerging clinical investigations indicates it may reduce morbidity associated with sedation and intubation. We systematically reviewed the efficacy of awake ECMO and provided evidence for clinical practitioners and researchers.

Design

Systematic review and trial sequential meta-analysis based on observational studies.

Data sources

Data was retrieved from seven databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database and Cochrane Library) up to 1 March 2024.

Eligibility criteria

We included observational studies that compared the differences in clinical outcomes between awake ECMO and non-awake ECMO in patients with cardiogenic shock.

Data extraction and synthesis

Two reviewers rigorously conducted literature retrieval, screening and data extraction. The RevMan software was used for data synthesis.

Results

Five retrospective observational studies involving 1044 patients with cardiogenic shock were included. Compared with non-awake ECMO, awake ECMO was associated with a lower mortality rate of patients with cardiogenic shock (OR=0.28; 95% CI, (0.15, 0.49); p<0.0001; I2=50%). Trial sequential analysis indicated that the sample mortality outcome reached the required information size. No significant differences were observed between the two groups on secondary outcomes such as the occurrence of ventilator-associated pneumonia, weaning from ECMO, tracheostomy, haemorrhage, thrombosis, limb ischaemia and nosocomial infection.

Conclusions

Implementing awake ECMO may result in better clinical outcomes in patients with cardiogenic shock. Because of the limited sample sizes and potential bias of the current studies, more rigorously designed large-scale trials are urgently needed to verify the above findings.

PROSPERO registration number

CRD42023407607.
Experiences of commissioning services for child and adolescent mental health in England (UK): a qualitative framework analysis
Authors: Allen Kate , Trethewey Samuel P , Mathews Frances , Price Anna , Newlove-Delgado Tamsin
Published: October 2024

Objectives

To explore commissioners’ experiences of commissioning services for child and adolescent mental health, their perspectives on the needs of their populations, the challenges they face and their needs for support and data.

Design

Qualitative study involving semi-structured interviews. All interviews were audio-recorded and transcribed verbatim. Data were analysed using framework analysis.

Setting

England, UK.

Participants

12 integrated care board commissioners, responsible for commissioning NHS England Child and Adolescent Mental Health Services (CAMHS).

Results

We identified five themes:‘reflections on role’; ‘priorities and tensions: working in a complex and evolving integrated care system’; ‘insights and evidence: the role and use of data and informants’; ‘children’s mental health in the limelight: influences and expectations’; and‘responding to need "CAMHS as the answer to everything"’. Combined, these themes highlight the integral role commissioners play in providing oversight over the local system and challenges to this role including disproportionate funding for services for child and adolescent mental health, different use and value ascribed to ‘qualitative’ and ‘quantitative’ data, rises in demand and the limited focus on early intervention and prevention.

Conclusions

CAMHS commissioners are currently negotiating a complex and changing political, social and economic environment with competing priorities and pressures. Our research indicates that commissioners require greater support as their roles continue to evolve.
Qualitative study exploring parenting among mothers and female caregivers living with the IPV, mental health and HIV syndemic in South Africa
Authors: Silima Mpho , Christofides Nicola Joan , Franchino-Olsen Hannabeth , Woollett Nataly , Meinck Franziska
Published: October 2024

Background

In South Africa, women disproportionately bear the burden of intimate partner violence (IPV), HIV or AIDS, and poor mental health.

Objective

This study investigated parenting practices among women affected by IPV, HIV and poor mental health syndemics.

Study setting

The study was conducted in two sites, a peri-urban area and a rural area in Mpumalanga, South Africa.

Study design

A qualitative research design using a narrative approach with in-depth interviews supported by arts-based methods was used. Data were analysed thematically using MAXQDA (2022).

Participants

20 women aged 20–60 who screened positive for HIV, IPV and/or poor mental health in a larger three-generational cohort study were selected.

Results

Living with the syndemics exacerbated socioeconomic challenges that often translated into an inability to meet basic child needs. Socioeconomic challenges also led to more harsh parenting practices among women living with IPV-Mental Health and HIV-Mental Health syndemics. Due to lack of trust from family members, women living with the HIV-Mental Health-IPV syndemic were often separated from their children. These women exhibited less harsh parenting practices than the women in the other syndemic groups when they did see their children. A history of childhood trauma, leading to overprotective parenting, was common across the groups except for the IPV-Mental Health group. Women in the IPV-Mental Health group often had strained relations with their children’s fathers, affecting their engagement and connection with their children.

Conclusion

The study underlines challenges experienced by women with IPV-Mental Health, HIV-Mental Health and HIV-Mental Health-IPV syndemics. The overlap of these epidemics strains women’s relationships and affects women’s parenting practices detrimentally resulting in an inadequate provision for children’s needs.
Investigating the impact of a multicomponent positive participatory organisational intervention on burnout in New Zealand emergency department staff: a prospective, multisite, before and after, mixed methods study
Authors: Nicholls Mike , Anderson Natalie , Jarden Rebecca , Selak Vanessa , Frampton Chris , Dalziel Stuart R
Published: October 2024

Introduction

The well-being of healthcare workers (HCWs) is critical to providing excellent care. Recent evidence concerns the well-being of emergency department (ED) HCWs in New Zealand, with high levels of burnout found in a 2020 survey. This threat to providing high-quality acute care warrants improvement interventions. The causes of burnout are complex and multifactorial, the solutions are not straightforward.

Methods and analysis

A prospective, multisite, before and after, mixed methods study assessing a multicomponent intervention, adaptable to local context, that targets three organisation levels (the individual, the group and the system levels) and meaningfully involves frontline HCWs may reduce HCW burnout and improve HCW well-being. Individual HCWs will choose from three individual-level psychological interventions and participate in those most appropriate for them. Local champions will decide which group-level intervention their ED will use. The system-level intervention will build capacity and capability for quality improvement (QI) with QI training and the establishment of a Quality Improvement Learning System. This system-level intervention has several important features that may ultimately empower HCWs to contribute to improving the quality of ED healthcare.

We will enrol nine EDs, from which there will be at least 900 HCW participants. EDs will be enrolled in three waves from March 2023 to April 2024, with interventions taking place in each ED over 12 months.

Methods of assessment will include baseline and repeat survey measures of burnout and well-being. Process evaluation at each ED will provide details of context, the intervention and the fidelity of the implementation.

Ethics and dissemination

Ethics committee approval was provided, with locality approval at each site.

Individual site feedback will be provided to each ED and executive leadership. Dissemination of findings will be through publication in peer-reviewed journals, presentation at national and international scientific meetings and through national healthcare quality bodies.

Trial registration number

Australia New Zealand Clinical Trials Registry (ACTRN12623000342617).