bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of HIV testing and associated factors among young adolescents in Eswatini: a secondary data analysis
Authors: Jung Mi Sook , Dlamini Nondumiso Satiso , Cui Xirong , Cha Kyeongin
Published: November 2022

Background

HIV testing is a crucial starting point for prevention, early diagnosis, and treatment of HIV. Sub-Saharan Africa has the highest global HIV/AIDS prevalence and mortality, yet HIV testing remains sub-optimal. Thus, this study aimed to identify the prevalence of HIV testing and associated factors among young adolescents aged 10 to 14 years in Eswatini, a country with the highest HIV prevalence in the world.

Methods

Data were obtained from Swaziland HIV Incidence Measurement Survey between 2016 and 2017 (SHIMS 2), an internationally supported national survey aimed at combating HIV/AIDS. A total of 739 young adolescents aged 10 to 14 years were selected for the final analysis after deleting cases with missing values for the key variables. The effects of demographic characteristics, HIV knowledge, HIV risk perception, belief about HIV testing, perceived service accessibility, and parent-child sexual and reproductive health communication on lifetime HIV testing as an outcome variable, were explored using multivariable logistic regression.

Results

Only 52.0% of young adolescents reported “ever tested” for HIV in their lifetime. Age (OR = 0.81, 95% CI = 0.73–0.90), residence (OR = 0.56, 95% CI = 0.43–0.74), and perceived service accessibility (OR = 3.10, (95% CI = 1.47–6.56) were identified as important factors associated with receiving HIV testing among young adolescents.

Conclusions

A low rate of HIV testing was identified among young adolescents in Eswatini compared to the intended global goal of HIV testing coverage. Our findings suggested the importance of young adolescent-friendly educational and environmental interventions needed to improve the prevalence of HIV testing by reducing misperceptions about the risk of HIV and alleviating environmental constraints to access to HIV services.
The structure of social support: a multilevel analysis of the personal networks of people with severe mental disorders
Authors: Wyngaerden François , Vacca Raffaele , Dubois Vincent , Lorant Vincent
Published: November 2022

Background

For psychiatric service users suffering from severe mental disorders, the social support provided by personal social networks is essential for living a meaningful life within the community. However, the importance of the support received depend on the relations between the providers of social support. Yet this hasn’t been addressed in the literature so far for people with severe mental disorders. This article seeks to investigate how characteristics of service users with severe mental disorders, their social contacts, and the pattern of relationships between those contacts influence the distribution and provision of social support to people with severe mental disorders.

Methods

We collected personal network data relating to 380 psychiatric service users from a random sample of health care providers in Belgium. We computed various measures of the structure of those networks and of the position of support persons within those networks. We conducted a multilevel analysis of the importance of the support provided by each support persons.

Results

The results show that the more central a support person was in the network of a service user, the more important his or her support was considered to be by the service user. Also, the denser the network in which a support person was embedded, the less important was the support he or she offers, but only for hospitalised service users.

Conclusion

These finding highlight the collective dimension of social support. We discuss the implications for the organisation of mental health care.
‘He was a brilliant student but became mad like his grandfather’: an exploratory investigation on the social perception and stigma against individuals living with mental health problems in Bangladesh
Authors: Shohel Tunvir Ahamed , Nasrin Nishad , Farjana Fariha , Shovo Taufiq-E-Ahmed , Asha Aisha Rahman , Heme Morsheda Akter , Islam Ashraful , Paul Pranto , Hossain Md. Tanvir
Published: November 2022

Background

Worldwide, mental health issues constitute a substantial threat to people’s social, economic, and mental well-being and contribute significantly to many fatalities each year. In Bangladesh, people with mental health issues typically delay contacting health professionals because they prefer traditional or religious healers. Moreover, the situation is exacerbated by a lack of awareness, social stigma, and negative perception of sufferers of mental health issues on the part of families and the community. Therefore, this paper investigates the social perception and stigmatization of individuals living with mental health problems and their caregivers in Khulna, Bangladesh.

Methods

Data were collected from university students with concurring mental health issues as well as their closest caregivers, who had in-depth knowledge of the problem and a willingness to take care of the individuals with mental health issues. Following the criteria for data collection, eight individuals living with mental health problems and five caregivers were purposively selected for this research. A semi-structured in-depth interview guide was used for the confidential data collection process, which took place in November and December 2021, and each interview lasted 40–50 min on average.

Results

This study used thematic analysis to present the results; the findings showed that: individuals afflicted with mental health problems sought both medical and spiritual support to recover. Those with mental health issues who received positive family support recovered relatively faster than those who did not. However, negative social perception and stigmatization were the key impediments for individuals suffering from mental health problems and their families, as they found it difficult to discuss their issues with relatives and communities when attempting to access support or seek remedies. Moreover, the commonality of social stigmas, such as labeling mental health problems as equal to ‘madness,’ hindered disclosure to family members, peers, and the community.

Conclusion and recommendations

In Bangladesh, the majority of individuals living with mental health problems are stigmatized and do not receive emotional support. Hence, we suggest nationwide community-based awareness-building programs to promote more positive perceptions of the fight against mental health disorders. Furthermore, counseling and awareness-building programs for effective discouragement of non-scientific remedies such as spiritual healing, as well as diagnosis and medication at the primary stage of sickness, are recommended for early detection and better medical assistance.
Patients with allergic asthma have lower risk of severe COVID-19 outcomes than patients with nonallergic asthma
Authors: Murphy Thomas R. , Busse William , Holweg Cecile T. J. , Rajput Yamina , Raimundo Karina , Meyer Craig S. , Seetasith Arpamas , Gupta Sachin , Iqbal Ahmar , Kaner Robert J.
Published: November 2022

Background

Although asthma does not appear to be a risk factor for severe coronavirus disease 2019 (COVID-19), outcomes could vary for patients with different asthma subtypes. The objective of this analysis was to compare COVID-19 outcomes in real-world cohorts in the United States among patients with asthma, with or without evidence of allergy.

Methods

In a retrospective analysis of the COVID-19 Optum electronic health record dataset (February 20, 2020–January 28, 2021), patients diagnosed with COVID-19 with a history of moderate-to-severe asthma were divided into 2 cohorts: those with evidence of allergic asthma and those without (nonallergic asthma). After 1:1 propensity score matching, in which covariates were balanced and potential bias was removed, COVID-19 outcomes were compared between cohorts.

Results

From a COVID-19 population of 591,198 patients, 1595 patients with allergic asthma and 8204 patients with nonallergic asthma were identified. After propensity score matching (n = 1578 per cohort), risk of death from any cause after COVID-19 diagnosis was significantly lower for patients with allergic vs nonallergic asthma (hazard ratio, 0.48; 95% CI 0.28–0.83; P = 0.0087), and a smaller proportion of patients with allergic vs nonallergic asthma was hospitalized within − 7 to + 30 days of COVID-19 diagnosis (13.8% [n = 217] vs 18.3% [n = 289]; P = 0.0005). Among hospitalized patients, there were no significant differences between patients with allergic or nonallergic asthma in need for intensive care unit admission, respiratory support, or COVID-19 treatment.

Conclusions

Asthma subtype may influence outcomes after COVID-19; patients with allergic asthma are at lower risk for hospitalization/death than those with nonallergic asthma.
Adjacent segment disease after minimally invasive transforaminal lumbar interbody fusion for degenerative lumbar diseases: incidence and risk factors
Authors: Yuan Chao , Zhou Jing , Wang Liran , Deng Zhongliang
Published: November 2022

Study design

Retrospective study.

Objectives

To explore the incidence and risk factors for symptomatic adjacent segment disease (ASD) in patients enveloped in degenerative lumbar diseases after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF).

Methods

Data were retrospectively analyzed on 744 patients who underwent MIS-TLIF for degenerative lumbar diseases in our hospital from October 2012 to December 2018. The patients were divided into the ASD group and non-ASD (N-ASD) group on the basis of developing ASD at follow-up, and then the incidence of ASD was calculated. Clinical and radiological risk factors were assessed over time to determine their association with ASD by excluding less important factors.

Results

Data were missing for 26 patients, while a total of 718 patients were successfully monitored after MIS-TLIF. Of the 718 individuals participated in the study, 34 (4.7%) patients plagued by ASD required surgical intervention. The average onset time of ASD was 62.7 ± 15.1 months. Univariate analysis results shows that age, bone mineral density (BMD), body mass index (BMI), preoperative adjacent intervertebral disc height and preoperative adjacent segment disc degeneration were significantly different between the ASD and N-ASD groups (p < 0.05). The logistic regression analysis results demonstrated that BMD (p = 0.039, OR = 0.986, 95% CI 0.899–1.115), BMI (p = 0.041, OR = 1.119, 95% CI 1.103–2.397), and preoperative adjacent intervertebral disc degeneration (p = 0.023, OR = 1.215, 95% CI 1.015–1.986) may be seen as risk factors for ASD after MIS-TLIF.

Conclusions

The incidence of ASD was about 4.7% in patients suffer from degenerative lumbar diseases after MIS-TLIF. BMD, BMI and preoperative adjacent intervertebral disc degeneration might be the risk factors for the occurrence of ASD after MIS-TLIF. Our research also suggested that patients with lower BMD, higher BMI and disc preoperative adjacent segment disc degeneration were more likely to develop ASD after MIS-TLIF.
Effectiveness of fluoride-containing toothpastes associated with different technologies to remineralize enamel after pH cycling: an in vitro study
Authors: Fernandes Nayanna Lana Soares , Silva José Gabriel Victor Costa , de Sousa Elizabeth Barreto Galvão , D’Alpino Paulo Henrique Perlatti , de Oliveira Andressa Feitosa Bezerra , de Jong Elbert de Josselin , Sampaio Fábio Correia
Published: November 2022

Background

To evaluate the efficacy of fluoride-containing toothpastes with different technologies to remineralize artificial caries lesions in enamel.

Methods

Bovine enamel blocks were divided into three thirds: intact (untreated), demineralized (artificial caries lesion), and treated (caries lesion, pH cycling with dentifrices). Enamel blocks were randomly distributed into five groups (n = 12): Fluoride-free toothpaste, Colgate Oral Care (NC); Arginine-containing toothpaste, Colgate Total Daily Repair (PC); Silicate-based fluoride toothpaste: REFIX technology, regenerador + sensitive (RDC), NR-5 technology, Regenerate Enamel Science (RES), and NOVAMIN technology, Sensodyne Repair and Protect (SRP). The specimens were submitted to a pH cycling model for 6 days. The efficacy of the toothpastes was estimated by calculating the surface microhardness recovery (%SMHR) and the fluorescence recovery (ΔFRE) with quantitative light-induced fluorescence. The cross-sectional micromorphology of the enamel surface was also assessed using scanning electron microscopy. Elemental analyses (weight%) were determined with an energy-dispersive X-ray spectrometer (EDS). The results were compared to that of the control (NC). Data were statistically analyzed (5%).

Results

%SMHR could be ranked as follows: RDC = PC = RES = SRP > NC. Significantly higher %SMHR and ΔFRE means were observed after enamel treatment with RDC (22.7 and 46.9, respectively). PC (%SMHR = 18.8) was as efficacious as RDC to recover the surface microhardness with a significantly lower mean of ΔFRE (19.5). Only RDC was able to promote the formation of a mineralized layer on the surface of enamel enriched with silicon on the surface.

Conclusions

The silicate-based fluoride toothpaste containing REFIX technology demonstrated greater efficacy in the remineralizing artificial caries than the other products.
Professionals’ perspectives on how to address persistent oral health inequality among young children: an exploratory multi-stakeholder analysis in a disadvantaged neighbourhood of Amsterdam, the Netherlands
Authors: Balasooriyan Awani , Dedding Christine , Bonifácio Clarissa Calil , van der Veen Monique H.
Published: November 2022

Background

Oral health promotion interventions have had limited success in reaching families in disadvantaged neighbourhoods resulting in persistent oral health inequality. This qualitative study provides insight into professionals’ perspectives on children’s poor oral health (≤ 4 years), their perceptions of the roles and responsibilities, and opportunities for child oral health promotion strategies.

Methods

Thirty-Eight professionals from different domains (community, social welfare, general health, dental care, public health, private sector) working in a disadvantaged neighbourhood in Amsterdam, the Netherlands, participated through 24 semi-structured (group) interviews. Transcripts and notes were analysed through thematic analysis.

Results

Professionals indicate that unhealthy diet, children’s non-compliance, poor parental coping, parental low oral health literacy, parent’s negative attitude, family’s daily struggles, and insufficient emphasis on childhood caries prevention in dental practices, general healthcare and social welfare organisations, underlie poor oral health. They hold parents most responsible for improving young children’s oral health, but recognise that families’ vulnerable living circumstances and lack of social support are important barriers. Interestingly, non-dental professionals acknowledge their beneficial role in child oral health promotion, and dental professionals stress the need for more collaboration.

Conclusion

A broad child-, parental-, and societal-centred educational communication strategy is perceived as promising. Professionals working within and outside the dental sector acknowledge that local and collective action is needed. This involves a better understanding of family’s complex daily reality. Furthermore, intensifying child oral health knowledge in dental practices is essential in collaboration with families, general health and social welfare organisations.
Barriers and facilitators for coherent rehabilitation among people with inflammatory arthritis – a qualitative interview study
Authors: Feddersen Helle , Søndergaard Jens , Andersen Lena , Munksgaard Bettina , Primdahl Jette
Published: November 2022

Background

People with chronic diseases have contact with several different professionals across hospital wards, municipality services and general practice and often experience lack of coherence. The purpose was to explore perceived barriers and facilitators to coherent rehabilitation pathways for health care users with inflammatory arthritis and how coherence can be improved.

Methods

Semi-structured individual interviews were conducted before a planned inpatient rehabilitation stay, 2-3 weeks and 4-6 months after discharge. Thematic reflexive analysis guided the analysis of data. Concepts of person-centred care, complex adaptive systems and integrated care were applied in the interpretations.

Results

In all, 11 participants with IA were included. There was one overarching theme, The importance of a person-centred approach, illuminating the significance of professionals who respect healthcare user’ preferences. To use a person-centred approach, demands professionals who are interested in exploring the persons own values, preferences and experiences and incorporate these when planning care and rehabilitation.Connected to the overarching theme, three sub-themes were derived; 1) Experiences of empowerment and dis-empowerment, covering that most want to be in control and act themselves, but felt overwhelmed and lost energy and they tended to give up; 2) Experiences of communication and coordination, encompass how people feel forced to take on coordination and communication tasks themselves although they do not always feel qualified for this. Some asked for a coordination person and 3) Facing everyday life after discharge, covering how initiatives taken by professionals were not always experienced as helpful after discharge. Some gave up and some tried to find alternative paths themselves.

Conclusion

Professionals taking a person-centred approach facilitated coherent rehabilitation pathways. This encompassed care with respect for individual needs and professionals who empowered patients to self-management. Furthermore, to be aware that interprofessional communication and coordination need to take place both between professional within the same department, between departments and between professionals in different sectors.

After discharge, some patients were challenged in their everyday life when trying to follow the advice from the professionals. Professionals, who do not use a person-centred approach, hinder coherence. Patients thus feel compelled to take on communication and coordination tasks.
Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events
Authors: Sakuma Masashi , Iimuro Satoshi , Shinozaki Tomohiro , Kimura Takeshi , Nakagawa Yoshihisa , Ozaki Yukio , Iwata Hiroshi , Miyauchi Katsumi , Daida Hiroyuki , Suwa Satoru , Sakuma Ichiro , Nishihata Yosuke , Saito Yasushi , Ogawa Hisao , Matsuzaki Masunori , Ohashi Yasuo , Taguchi Isao , Toyoda Shigeru , Inoue Teruo , Nagai Ryozo
Published: November 2022

Background

Aggressive lipid lowering by high-dose statin treatment has been established for the secondary prevention of coronary artery disease (CAD). Regarding the low-density lipoprotein cholesterol (LDL-C) level, however, the “The lower is the better” concept has been controversial to date. We hypothesized that there is an optimal LDL-C level, i.e., a “threshold” value, below which the incidence of cardiovascular events is no longer reduced. We undertook a subanalysis of the REAL-CAD study to explore whether such an optimal target LDL-C level exists by a novel analysis procedure to verify the existence of a monotonic relationship.

Methods

For a total of 11,105 patients with CAD enrolled in the REAL-CAD study, the LDL-C level at 6 months after randomization and 5-year cardiovascular outcomes were assessed. We set the “threshold” value of the LDL-C level under which the hazards were assumed to be constant, by including an artificial covariate max (0, LDL-C − threshold) in the Cox model. The analysis was repeated with different LDL-C thresholds (every 10 mg/dl from 40 to 100 mg/dl) and the model fit was assessed by log-likelihood.

Results

For primary outcomes such as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization, the model fit assessed by log-likelihood was best when a threshold LDL-C value of 70 mg/dl was assumed. And in the model with a threshold LDL-C ≥ 70 mg/dl, the hazard ratio was 1.07 (95% confidence interval 1.01–1.13) as the LDL-C increased by 10 mg/dl. Therefore, the risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dl, but when the level was further reduced, the risk was independent of LDL-C.

Conclusions

Our analysis model suggests that a “threshold” value of LDL-C might exist for the secondary prevention of cardiovascular events in Japanese patients with CAD, and this threshold might be 70 mg/dl for primary composite outcomes.

Trial registration

http://www.clinicaltrials.gov. Unique identifier: NCT01042730.
The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes
Authors: Sun Xiaoying , Liu Lili , Wan Ting , Huang Qidan , Chen Jieping , Luo Rongzhen , Liu Jihong
Published: November 2022

Background

We investigate the correlation between programmed cell death-ligand 1 (PD-L1) and tumor-associated immune cell (TAIC) density in small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) and their correlation with clinicopathologic features.

Methods

PD-L1 and mismatch repair protein (MMR) expression in cancer cells and the density of TAIC were evaluated by immunohistochemistry in 89 SCNEC patients. The combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) of PD-L1 were measured, along with their correlation with clinicopathologic features in SCNEC patients using statistical analyses.

Results

CPS of PD-L1 ≥ 1 was seen in 68.5% of patients, positive TPS and ICS of PD-L1 were detected in 59.6% and 33.7% of patients, respectively. PD-L1CPS was higher in tumor-infiltrating immune cells (r = 0.387, p = 0.001) and positively correlated with programmed cell death-1 and forkhead box P3 + regulatory T cell (FOXP3 + Treg) infiltration (r = 0.443, p < 0.001; r = 0.532, p < 0.001). There was no statistical correlation between PD-L1 and MMR status. PD-L1CPS and PD-L1ICS positivity were independent prognostic factors, correlating with a favorable survival (HR (95%CI) = 0.363(0.139–0.950), p = 0.039 and HR (95% CI) = 0.199(0.050–0.802), p = 0.023, respectively). PD-L1ICS positivity was an independent indicator of recurrence in SCNEC patients and associated with better disease-free survival (HR (95% CI) = 0.124(0.036–0425), p = 0.001). TAIC and MMR levels had no statistical impact on survival results.

Conclusions

PD-L1 positivity was seen in over half of SCNEC tumors. It may work synergistically with FOXP3 + Treg and other infiltrating immune cells to support an adaptive immune response. PD-L1 positivity may be a favorable prognostic factor in SCNEC.
A malaria knowledge, attitudes and practice survey in a rural community in Guinea
Authors: Ravi Nirmal , Holsted Erin , Kadiebwe Barclay , Salthouse Abigail , Sattar Amer
Published: November 2022

Background

Malaria is the top public health problem in the Republic of Guinea, with more than 4 million cases and 10,000 deaths in 2021 among a population of approximately 13 million. It is also the second highest cause of death there. The purpose of this quantitative survey in a rural area of Guinea was to understand knowledge, attitudes, and practices (KAP) about malaria and to assess water and sanitation practices among community members.

Methods

In 2016, the authors conducted a cross-sectional household survey in Timbi-Touni, Guinea using community workers. The survey included respondent demographic characteristics, malaria knowledge, child health, water and sanitation, and health services access. Malaria knowledge and sleeping under bed nets were the primary outcome variables and multiple logistic regression was used to determine odds ratios.

Results

Majority of the respondents were women (89.41%) and had never been to school (71.18%). Slightly more than half the children were reported to have ever had malaria and 45% reported to have ever had diarrhoea. There was no statistically significant association between gender or level of education and malaria knowledge. Eighty six percent of respondents had received a free bed net during national campaigns and 61% slept under a bed net the night before the survey. Knowing mosquitoes to be the cause of malaria and receiving free bed net were significantly associated with sleeping under a bed net. There was no statistically significant association between drinking water source and malaria or diarrhoea.

Conclusions

Both malaria and diarrhoea were considered to be serious illnesses for adults and children by nearly all respondents. Receiving free bed nets and having correct knowledge about malaria were the greatest predictors of sleeping under a bed net. Insights from this detailed KAP survey—such as focusing on radio to transmit malaria prevention information and reinforcing free malaria treatments—can guide policy makers and practitioners who design and implement malaria control and prevention measures in Guinea.
How long is the last mile? Evaluating successful malaria elimination trajectories
Authors: Cohen Justin M. , Kandula Deepika , Smith David L. , Le Menach Arnaud
Published: November 2022

Background

Many national malaria programmes have set goals of eliminating malaria, but realistic timelines for achieving this goal remain unclear. In this investigation, historical data are collated on countries that successfully eliminated malaria to assess how long elimination has taken in the past, and thus to inform feasible timelines for achieving it in the future.

Methods

Annual malaria case series were sought for 56 successful elimination programmes through a non-systematic review. Up to 40 years of annual case counts were compiled leading up to the first year in which zero locally acquired or indigenous cases were reported. To separate the period over which effective elimination efforts occurred from prior background trends, annual case totals were log transformed, and their slopes evaluated for a breakpoint in linear trend using thesegmentedpackage in R. The number of years from the breakpoint to the first year with zero cases and the decline rate over that period were then calculated. Wilcox-Mann-Whitney tests were used to evaluate whether a set of territory characteristics were associated with the timelines and decline rates.

Results

Case series declining to the first year with zero cases were compiled for 45/56 of the candidate elimination programmes, and statistically significant breakpoints were identified for 42. The median timeline from the breakpoint to the first year with zero local cases was 12 years, over which cases declined at a median rate of 54% per year. Prior to the breakpoint, the median trend was slightly decreasing with median annual decline of < 3%. Timelines to elimination were fastest among territories that lacked land boundaries, had centroids in the Tropics, received low numbers of imported cases, and had elimination certified by the World Health Organization.

Conclusion

The historical case series assembled here may help countries with aspirations of malaria elimination to set feasible milestones towards this goal. Setting goals for malaria elimination on short timescales may be most appropriate in isolated, low importation settings, such as islands, while other regions aiming to eliminate malaria must consider how to sustainably fund and maintain vital case management and vector control services until zero cases are reached.
Comparative effect of artemether-lumefantrine and artesunate-amodiaquine on gametocyte clearance in children with uncomplicated Plasmodium falciparum malaria in Madagascar
Authors: Rakotoarisoa Malalanandrianina A. , Fenomanana Jocia , Dodoson Bronislaw Tchesterico , Andrianaranjaka Voahangy Hanitriniaina I. , Ratsimbasoa Arsène
Published: November 2022

Background

Gametocytes are the sexual stages ensuring continuity of the development cycle of the parasite, as well as its transmission to humans. The efficacy of artemisinin-based anti-malarials against asexual stages of Plasmodium has been reported in Madagascar, but their effects on gametocytes are not well documented. The present study aims to determine the emergence of gametocyte and gametocyte clearance after artesunate-amodiaquine (ASAQ) or artemether-lumefantrine (AL) treatment in children with uncomplicated Plasmodium falciparum malaria in 5 regions of Madagascar.

Methods

558 children with uncomplicated P. falciparum malaria, aged between 1 and 15 years, were assigned randomly to AL or ASAQ treatment. They come from 5 regions of Madagascar with different epidemiological facies related to malaria: Ankilivalo, Benenitra, Ampanihy, Ankazomborona and Matanga. Gametocytes were identified by microscopy, from t blood smears at day 1, day 2, day 3, day 7, day 14, day 21 and day 28 after treatment.

Results

At baseline, 9.7% (54/558) children [95% CI: 7.4–12.5%] had detectable gametocyte by microscopy. Among the 54 enrolled children, gametocytes emergence rate was high during the first days of treatment in both treatment arms (AL and ASAQ), especially on day 1. Gametocytes were undetectable from day 14 for AL arm while for ASAQ arm, gametocyte carriage was gradually decreased but persisted until day 21.

Conclusion

This study demonstrates that AL has a more rapid effect on gametocyte clearance compared to ASAQ in children with uncomplicated Plasmodium falciparum malaria.
Neuroinflammation regulates the balance between hippocampal neuron death and neurogenesis in an ex vivo model of thiamine deficiency
Authors: Cassiano Larissa M. G. , Oliveira Marina S. , Pioline Jeanne , Salim Anna C. M. , Coimbra Roney S.
Published: November 2022

Background

Thiamine (vitamin B1) is a cofactor for enzymes of central energy metabolism and its deficiency (TD) impairs oxidative phosphorylation, increases oxidative stress, and activates inflammatory processes that can lead to neurodegeneration. Wernicke–Korsakoff syndrome (WKS) is a consequence of chronic TD, which leads to extensive neuronal death, and is associated with neuropathological disorders, including cognitive deficits and amnesia. The hippocampus is one of the brain areas most affected by WKS. B1 replacement may not be enough to prevent the irreversible cognitive deficit associated with WKS.

Materials and methods

An organotypic hippocampal slice culture (OHC) model was developed to investigate, using immunofluorescence and confocal microscopy and transcriptome analysis, the molecular mechanisms underlying the neurodegeneration associated with TD. The effect of anti-inflammatory pharmacological intervention with resveratrol (RSV) was also assessed in B1-deprived OHCs.

Results

In OHCs cultured without B1, neuronal density decayed after 5 days and, on the 7th day, the epigenetic markings H3K4me3 and H3K9me3 were altered in mature neurons likely favoring gene transcription. Between the 7th and the 14th day, a pulse of neurogenesis was observed followed by a further massive neuron loss. Transcriptome analysis at day nine disclosed 89 differentially expressed genes in response to B1 deprivation. Genes involved in tryptophan metabolism and lysine degradation KEGG pathways, and those with Gene Ontology (GO) annotations related to the organization of the extracellular matrix, cell adhesion, and positive regulation of synaptic transmission were upregulated. Several genes of the TNF and FoxO signaling pathways and with GO terms related to inflammation were inhibited in response to B1 deprivation. Nsd1, whose product methylates histone H3 lysine 36, was upregulated and the epigenetic marking H3K36me3, associated with negative regulation of neurogenesis, was increased in neurons. Treating B1-deprived OHCs with RSV promoted an earlier neurogenesis pulse.

Conclusion

Neuroregeneration occurs in B1-deficient hippocampal tissue during a time window. This phenomenon depends on reducing neuroinflammation and, likely, on metabolic changes, allowing acetyl-CoA synthesis from amino acids to ensure energy supply via oxidative phosphorylation. Thus, neuroinflammation is implicated as a major regulator of hippocampal neurogenesis in TD opening a new search space for treating WKS.
Androgen receptor function and targeted therapeutics across breast cancer subtypes
Authors: Kolyvas Emily A. , Caldas Carlos , Kelly Kathleen , Ahmad Saif S.
Published: November 2022

Despite significant progress in breast cancer (BC) therapy, it is globally the most commonly diagnosed cancer and leads to the death of over 650,000 women annually. Androgen receptor (AR) is emerging as a potential new therapeutic target in BC. While the role of AR is well established in prostate cancer (PCa), its function in BC remains incompletely understood. Emerging data show that AR’s role in BC is dependent on several factors including, but not limited to, disease subtype, tumour microenvironment, and levels of circulating oestrogens and androgens. While targeting AR in PCa is becoming increasingly effective, these advances have yet to make any significant impact on the care of BC patients. However, this approach is increasingly being evaluated in BC and it is clear that improvements in our understanding of AR’s role in BC will increase the likelihood of success for AR-targeted therapies. This review summarizes our current understanding of the function of AR across BC subtypes. We highlight limitations in our current knowledge and demonstrate the importance of categorizing BC subtypes effectively, in relation to determining AR activity. Further, we describe the current state of the art regarding AR-targeted approaches for BC as monotherapy or in combination with radiotherapy.
Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker
Authors: Johansson Patricia , Laguna Teresa , Ossowski Julio , Pancaldi Vera , Brauser Martina , Dührsen Ulrich , Keuneke Lara , Queiros Ana , Richter Julia , Martín-Subero José I. , Siebert Reiner , Schlegelberger Brigitte , Küppers Ralf , Dürig Jan , Murga Penas Eva M. , Carillo-de Santa Pau Enrique , Bergmann Anke K.
Published: November 2022

Background

The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor αβ-positive CD8+ memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples.

Results

We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation.

Conclusions

DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed.
An educational video on long-acting reversible contraception as a counseling tool for postpartum adolescents
Authors: Santibenchakul Somsook , Thanativakul Kittithorn , Jaisamrarn Unnop
Published: November 2022

Objective

To assess the effects of using an animated local language educational video to counsel postpartum adolescents on the benefits and use of long-acting reversible contraception (LARC).

Materials and methods

A two-stage, single group, experimental study was conducted. A total of 124 female adolescents aged < 20 years who had given birth within the last six weeks participated in the study. An educational video and a questionnaire were developed and validated. Participants were asked to fill out a questionnaire on basic demographic data, contraception preferences, and 10 true/false statements to test general contraceptive knowledge, after which they were shown an educational video in a private room. Following this, participants completed the second part of the questionnaire that assessed their knowledge using the same true/false statements and contraception preferences administered earlier.

Results

The mean age (standard deviation) of participants was 18.1 (1.5) years. Participants’ mean age (SD) at the time of their first sexual intercourse was 16.2 (1.6) years. Among the 124 participants, 31 (25%) indicated that they would use LARC before viewing the educational video. After viewing the educational video, this number increased to 48 (38.7%). The participants’ knowledge score was independently associated with their preference to select LARC (adjusted odds ratio 1.46, 95% confidence interval 1.09- 1.97).

Conclusion

This study demonstrated that counseling tools such as animated local language educational video might effectively improve contraceptive knowledge and the preference for LARC in postpartum adolescents. An educational video regarding LARC could be used as a counseling tool for postpartum adolescents.
Rediscovering the Monk-Sculptor Ch’ŏnsin: The Missing Link between the Ŭngwŏn-In'gyun and Saengnan Schools of the Honam Area in the Late Chosŏn Period
Authors: Song Unsok
Published: November 2022

Of the monk-sculptor groups active in the Honam area in the southwest part of the Korean Peninsula during the late Chosŏn period, the Saengnan School was the largest, both in terms of the number of artists in the group and of the works they left behind. Studies of the group have largely focused on the sculpting activities of the Buddhist monk Saengnan (fl. late seventeenth to the early eighteenth century; 1663–1709) and his followers, while little is known about the origins of the school due to a lack of records about his formative years as an assistant. The recent discovery of four Buddhist parwŏn prayer texts has revealed that Saengnan spent the early years of his career as a sculptor assisting the monk-sculptors In'gyun and Ch’ŏnsin, who were key members of the Ŭngwŏn-In'gyun School that played a central role in the production of Buddhist sculptures in the early to late seventeenth century in the region. This study shows that the Saengnan School, the most productive group of monk-sculptors from the late seventeenth to the early eighteenth century in the Honam region, was a successor to the Ŭngwŏn-In'gyun School, through a comparative examination of these highly informative prayers and relevant Buddhist sculptures. My examination also reveals that the two schools were linked by Ch’ŏnsin, who studied sculpture under In'gyun, and in turn, taught Saengnan.
“All That He Seen Burnt a Hole in His Brain”
Authors: Waller Ryan
Published: November 2022

The title of this playlist comes from the chorus of Armand Hammer's “Rehearse with Ornette,” wherein billy woods repeats, “All that he seen burnt a hole in his brain/only came back to tell ’em bout them fucking flames.” This idea of a mind swallowed in shock, bellowing out its truth, is a deeply disturbing image and a generative point of entry into the psychic terror of black being in the afterlife of slavery. Thus the tracks in this playlist explore the impressionistic and visceral qualities of the Afro-Gothic mindset through songs that lyrically and sonically express themes of faith and grief as part of the soundtrack to everyday black life.
Position of meristems and the angles of the cell division plane regulate the uniqueness of lateral organ shape
Authors: Kinoshita Ayaka , Naito Makiko , Wang Zining , Inoue Yasuhiro , Mochizuki Atsushi , Tsukaya Hirokazu
Published: November 2022

Leaf meristem is a cell proliferative zone present in the lateral organ primordia. In this study, we examined how cell proliferative zones in primordia of planar floral organs and polar auxin transport inhibitor (PATI)-treated leaf organs differ from those of non-treated foliage leaves of Arabidopsis thaliana, with a focus on the accumulation pattern of ANGUSTIFOLIA3 (AN3) protein, a key element for leaf meristem positioning. We found that PATI-induced leaf shape changes were correlated with cell division angle but not with meristem positioning/size or AN3 localisation. In contrast, different shapes between sepals and petals compared with foliage leaves were associated with both altered meristem position, due to altered AN3 expression patterns, and different distributions of cell division angles. A numerical simulation showed that meristem position majorly affected the final shape but biased cell division angles had a minor effect. Taken together, these results suggest that the unique shapes of different lateral organs depend on the position of the meristem in the case of floral organs and cell division angles in the case of leaf organs with different auxin flow.
Maternal heterozygosity of Slc6a19 causes metabolic perturbation and congenital NAD deficiency disorder in mice
Authors: Cuny Hartmut , Bozon Kayleigh , Kirk Rosemary B. , Sheng Delicia Z. , Bröer Stefan , Dunwoodie Sally L.
Published: November 2022

Nicotinamide adenine dinucleotide (NAD) is a key metabolite synthesised from vitamin B3 or tryptophan. Disruption of genes encoding NAD synthesis enzymes reduces NAD levels and causes congenital NAD deficiency disorder (CNDD), characterised by multiple congenital malformations. SLC6A19 (encoding B0AT1, a neutral amino acid transporter), represents the main transporter for free tryptophan in the intestine and kidney. Here, we tested whether Slc6a19 heterozygosity in mice limits the tryptophan available for NAD synthesis during pregnancy and causes adverse pregnancy outcomes. Pregnant Slc6a19+/− mice were fed diets depleted of vitamin B3, so that tryptophan was the source of NAD during gestation. This perturbed the NAD metabolome in pregnant Slc6a19+/− females, resulting in reduced NAD levels and increased rates of embryo loss. Surviving embryos were small and exhibited specific combinations of CNDD-associated malformations. Our results show that genes not directly involved in NAD synthesis can affect NAD metabolism and cause CNDD. They also suggest that human female carriers of a SLC6A19 loss-of-function allele might be susceptible to adverse pregnancy outcomes unless sufficient NAD precursor amounts are available during gestation.

This article has an associated First Person interview with the first author of the paper.
An RNA granule for translation quality control in Saccharomyces cerevisiae
Authors: Dhaliwal James S. , Panozzo Cristina , Benard Lionel , Zerges William
Published: November 2022

Cytoplasmic RNA granules compartmentalize phases of the translation cycle in eukaryotes. We previously reported the localization of oxidized RNA to cytoplasmic foci called oxidized RNA bodies (ORBs) in human cells. We show here that ORBs are RNA granules in Saccharomyces cerevisiae. Several lines of evidence support a role for ORBs in the compartmentalization of no-go decay and ribosome quality control, the translation quality control pathways that recognize and clear aberrant mRNAs, including those with oxidized bases. Translation is required by these pathways and ORBs. Translation quality control factors localize to ORBs. A substrate of translation quality control, a stalled mRNA–ribosome–nascent-chain complex, localizes to ORBs. Translation quality control mutants have altered ORB numbers, sizes or both. In addition, we identify 68 ORB proteins by immunofluorescence staining directed by proteomics, which further support their role in translation quality control and reveal candidate new factors for these pathways.
Dual-Action Pt(IV) Prodrugs and Targeted Delivery in Metal-Organic Frameworks: Overcoming Cisplatin Resistance and Improving Anticancer Activity
Authors: Larasati Larasati , Lestari Witri Wahyu , Firdaus Maulidan
Published: November 2022

The conversion of cisplatin Pt(II) into a Pt(IV) complex is a strategy that can be used to overcome cisplatin resistance and side effects, and this involves the functionalization of the axial positions of cisplatin. Using ligands with bioactivity to target specific cancer cell species could lead to targeted treatment and mitigate severe side effects. Furthermore, enhanced cellular uptake could be used to overcome cisplatin resistance. Anchoring the “dual-acting” prodrug in self-assembled hybrid porous metal-organic frameworks (MOFs) has revealed an even more advanced treatment. The exceptional porosity allows high loading of the drug, and the easily tuned functional groups within the frameworks enable various interactions between the drug and the cargo material to optimize controlled release and prevent premature release. Some MOFs have also demonstrated cytotoxicity against several cancer lines. It is expected that the combination of the prodrug and active MOFs could generate a “triple-acting” anticancer agent for more enhanced cancer treatment. This review discusses the development of cisplatin modified with several prodrugs and its anticancer activity in several cancer cell lines. Furthermore, the review summarizes the involvement of cisplatin derivatives in MOFs, highlighting the slow, controlled, and targeted delivery of the drug and its anticancer activity.
Design and development of an eHealth intervention to support self-management in people with musculoskeletal disorders - ‘eHealth: It’s TIME’: a study protocol
Authors: Kelly Marie , Fullen Brona , Martin Denis , Bradley Colin , O'Mahony Billy , McVeigh Joseph G.
Published: November 2022

Background: Musculoskeletal disorders (MSDs) are a leading cause of global morbidity, with the burden expected to increase in the near future. Self-management, with the support of healthcare professionals, is recommended for many MSDs. However, frequent clinical contact is not feasible. Previous research has highlighted the need for a co-designed eHealth-mediated self-management follow-up support intervention which integrates remote monitoring and behavioural change. Thus, the current study aims to develop and design a user-centred, eHealth-mediated self-management support prototype for people with MSDs.

Methods: A three-step, iterative system development cycle will be utilised to develop and design the “eHealth: It’s TIME prototype”. The three-step process will include creating website features and content using two sequential focus groups with people with MSDs (n = 6 – 8); heuristic testing using the 10 heuristic principles of Nielsen (n = 5); and usability testing through in-person 60-minute interviews with people with MSDs (n = 3 – 5) and musculoskeletal physiotherapists (n = 3 – 5).

Conclusion: The eHealth: It’s TIME prototype will be a systematically developed, follow-up self-management support intervention guided by behavioural change theory and the preferences of end users.