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AnteayerPLOS ONE Medicine&Health

Distribution and dynamics of <i>Anopheles gambiae</i> s.l. larval habitats in three Senegalese cities with high urban malaria incidence

by Fatou Ndiaye, Abdoulaye Diop, Joseph Chabi, Katherine Sturm-Ramirez, Massila Senghor, El Hadji Diouf, Badara Samb, Seynabou Mocote Diedhiou, Omar Thiaw, Sarah Zohdy, Ellen Dotson, Doudou Sene, Mame Birame Diouf, Valerie Koscelnik, Lilia Gerberg, Abdoulaye Bangoura, Tiffany Clark, Ousmane Faye, Ibrahima Dia, Lassana Konate, El Hadji Amadou Niang

Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November–December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP).

Test-retest reliability of Latin American Group for Maturity (GDLAM) protocol in older women

by Álvaro Huerta Ojeda, Emilio Jofré-Saldía, Jimena Arriagada Molina, Patricia Rojas Quinchavil, María Paz Parada Toledo, Sergio Galdames Maliqueo, María-Mercedes Yeomans-Cabrera, Carlos Jorquera-Aguilera, Frano Giakoni-Ramirez, Maximiliano Bravo

Functional autonomy (FA) is a critical factor in determining the quality of life of older adults (OA), especially in the case of older women (OW), as they face a decline in FA in their later years of life. FA should be assessed early, using valid, reliable, and low-cost tests. This study evaluated the test-retest reliability of GDLAM and GDLAM autonomy index (GI) in OW. Thirty-nine OW (71.2 ± 6.50 years) participated in the study. A repeated measures design was used to compare the interday test-retest reliability of the five GDLAM tests (seconds) and the GI (points). The five tests represent activities of daily living, such as dressing or wandering around the house, while the GI provides a weighting of the results of the five tests. The analysis consisted of the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and coefficient of variation (CV). A CV ≤ 10% and an ICC ≥ 0.80 were considered acceptable reliability, whereas a CV ≤ 5% and an ICC ≥ 0.90 were considered high reliability. The outcome of the five tests, represented by the GI, showed high interday test-retest reliability (CV = 6.00% and ICC = 0.91). The results of this study demonstrate that the five tests of the GDLAM protocol and the GI have high interday test-retest reliability and good interday reproducibility. From a practical point of view, the GDLAM protocol allows the assessment of FA of community-dwelling OW, providing background for early diagnosis and, with it, the possibility of developing an individualized physical exercise prescription.

Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma

by Levi Matthies, Hendrik Amir-Kabirian, Medhanie T. Gebrekidan, Andreas S. Braeuer, Ulrike S. Speth, Ralf Smeets, Christian Hagel, Martin Gosau, Christian Knipfer, Reinhard E. Friedrich

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins–complete tumor removal while attempting to preserve viable tissue–remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial

by Afsoon Dadvar, Melika Jameie, Mehdi Azizmohammad Looha, Mohammadamin Parsaei, Meysam Zeynali Bujani, Mobina Amanollahi, Mahsa Babaei, Alireza Khosravi, Hamed Amirifard

Objectives

Caffeine’s potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS).

Methods

This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient’s perspective on MS-related QoL (MS-QoL), and Patients’ Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1).

Results

Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value Conclusions

Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time.

Trial registration

This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.

Factors affecting the efficiency of equine embryo transfer (EET) in polo mares under subtropical conditions of Pakistan

by Khalid Mahmood, Aijaz Ali Channa, Aamir Ghafoor, Amjad Riaz

Equine embryo transfer (EET) is a prominent technology in the equine breeding industry, and its efficacy is affected by a number of factors. The current study aimed to determine the effects of the breed of donor/recipient mares, estrus/ovulation induction treatment, cooled transportation of embryos, and synchrony between donor and recipient mares on the efficiency of the EET under subtropical conditions of Pakistan. A total of eighty-four (n = 84) Polo-playing donor mares (Argentino-polo = 41 and Anglo-Arab = 43) and seventy (n = 70) recipient mares (light breed = 26 and heavy breed = 44) were used for EET. The donor mares exhibiting natural estrus (n = 28) were detected by teaser a stallion, and corpus luteum (CL) having mares (n = 56) were treated with prostaglandin (150 μg of Cloprostenol) for estrus induction. The mares’ follicular growth was monitored through ultrasonography until the dominant follicle’s size reached 35 mm or more with a moderate to obvious uterine edema score. Afterward, the mares were treated either with GnRH, i.e., 50 μg of Lecirelin acetate (n = 41) or Ovusyn, i.e., 1500 IU hCG (n = 43). Insemination with chilled semen was performed 24 hours later. The embryos were collected non-surgically, 7 or 8 days after ovulation, from the donor mares. The collected embryos were transferred into the well-synchronized recipient mares as fresh (n = 44) or chilled (n = 26) embryos. The pregnancy after ET was checked through ultrasonography. Statistical analysis revealed that the embryo recovery rate (ERR) remained significantly higher (P0.05) affect the ERR. There was no significant effect of the type (fresh vs chilled), classification, and stage of development of embryo on pregnancy outcomes (P>0.05). ET pregnancy rate was significantly affected by the breed of recipient mares and ovulation synchrony between donor and recipient mares (P

The immune response of the whitefly <i>Trialeurodes vaporariorum</i> (Hemiptera: Aleyrodidae) when parasitized by <i>Eretmocerus eremicus</i> (Hymenoptera: Aphelinidae)

by Jorge Contreras-Garduño, Pedro Torres-Enciso, Ricardo Ramirez-Romero

In insects, the innate immune system is subdivided into cellular and humoral defenses. When parasitoids attack insects, both reactions can be activated and notably, the phenoloxidase (PO) cascade and lytic activity are part of both cellular and humoral defenses. However, to our knowledge, no study has characterized any immune response of the whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) to the attack of Eretmocerus eremicus (Hymenoptera: Aphelinidae). Therefore, the first objective of the present study was to determine whether whitefly nymphs recently parasitized by E. eremicus exhibit any immune response. For this, we estimate the level of prophenoloxidase (proPO), phenoloxidase (PO), and lytic activity by colorimetric assays. A second objective was to assess whether the observed whitefly immune response could be related to a previously reported preference of the predator Geocoris punctipes (Hemiptera: Lygaeidae) for non-parasitized nymphs. We therefore offered non-parasitized and recently parasitized nymphs to the predator. Our results show that parasitism of whitefly nymphs by E. eremicus induced a highly estimated level of proPO and PO, and a lower level of lytic activity. In addition, we found that G. punctipes did not show a preference for non-parasitized over recently parasitized nymphs. The nymphs of T. vaporariorum activated the PO pathway against E. eremicus; however, the increase in proPO and PO levels was traded-off with decreased lytic activity. In addition, the previously reported preference for non-parasitized nymphs was not seen in our experiments, indicating that the induced immune response did not affect predator behavior by G. punctipes.

Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker

by Amir Hossein Behnoush, Amirmohammad Khalaji, Shaghayegh Khanmohammadi, Parsa Alehossein, Behrad Saeedian, Parnian Shobeiri, Antonio L. Teixeira, Nima Rezaei

Background

Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM.

Methods

A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI).

Results

Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively.

Conclusion

Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker’s diagnostic and prognostic value should be further investigated in future studies.

Comparative analysis of silver-nanoparticles and whey-encapsulated particles from olive leaf water extracts: Characteristics and biological activity

by Hanem M. M. Mansour, Mohamed G. Shehata, Eman M. Abdo, Mona Mohamad Sharaf, El-sayed E. Hafez, Amira M. Galal Darwish

Nanotechnology applications have been employed to improve the stability of bioactive components and drug delivery. Natural-based extracts, especially olive leaf extracts, have been associated with the green economy not only as recycled agri-waste but also in the prevention and treatment of various non-communicable diseases (NCDs). The aim of this work was to provide a comparison between the characteristics, biological activity, and gene expression of water extract of olive leaves (OLE), green synthesized OLE silver nanoparticles (OL/Ag-NPs), and OLE whey protein capsules (OL/WPNs) of the two olive varieties, Tofahy and Shemlali. The particles were characterized by dynamic light scattering, scanning electron microscope (SEM), and Fourier transform infrared. The bioactive compounds of the preparations were evaluated for their antioxidant activity and anticancer effect on HCT-116 colorectal cells as well as for their regulatory effects on cytochrome C oxidase (Cox1) and tumor necrosis factor α (TNF-α) genes. (OL/Ag-NPs) were found to be smaller than (OL/WPNs) with sizes of (37.46±1.85 and 44.86±1.62 nm) and (227.20±2.43 and 553.02±3.60 nm) for Tofahy and Shemlali, respectively. SEM showed that Shemlali (OL/Ag-NPs) had the least aggregation due to their highest Ƹ-potential (-31.76 ± 0.87 mV). The preparations were relatively nontoxic to Vero cells (IC50 = 151.94–789.25 μg/mL), while they were cytotoxic to HCT-116 colorectal cells (IC50 = 77.54–320.64 μg/mL). Shemlali and Tofahy OLE and Tofahy OL/Ag-NPs had a higher selectivity index (2.97–7.08 μg/mL) than doxorubicin (2.36 μg/mL), indicating promising anticancer activity. Moreover, Shemlali preparations regulated the expression of Cox1 (up-regulation) and TNF-α (down-regulation) on HCT-116 cells, revealing their efficiency in suppressing the expression of genes that promote cancer cell proliferation. (OL/Ag-NPs) from Tofahy and Shemlali were found to be more stable, effective, and safe than (OL/WPNs). Consequently, OL/Ag-NPs, especially Tofahy, are the best and safest nanoscale particles that can be safely used in food and pharmaceutical applications.

Deciphering the immune landscape of head and neck squamous cell carcinoma: A single-cell transcriptomic analysis of regulatory T cell responses to PD-1 blockade therapy

by Adib Miraki Feriz, Fatemeh Bahraini, Arezou Khosrojerdi, Setareh Azarkar, Seyed Mehdi Sajjadi, Edris HosseiniGol, Mohammad Amin Honardoost, Samira Saghafi, Nicola Silvestris, Patrizia Leone, Hossein Safarpour, Vito Racanelli

Immunotherapy is changing the Head and Neck Squamous Cell Carcinoma (HNSCC) landscape and improving outcomes for patients with recurrent or metastatic HNSCC. A deeper understanding of the tumor microenvironment (TME) is required in light of the limitations of patients’ responses to immunotherapy. Here, we aimed to examine how Nivolumab affects infiltrating Tregs in the HNSCC TME. We used single-cell RNA sequencing data from eight tissues isolated from four HNSCC donors before and after Nivolumab treatment. Interestingly, the study found that Treg counts and suppressive activity increased following Nivolumab therapy. We also discovered that changes in the CD44-SSP1 axis, NKG2C/D-HLA-E axis, and KRAS signaling may have contributed to the increase in Treg numbers. Furthermore, our study suggests that decreasing the activity of the KRAS and Notch signaling pathways, and increasing FOXP3, CTLA-4, LAG-3, and GZMA expression, may be mechanisms that enhance the killing and suppressive capacity of Tregs. Additionally, the result of pseudo-temporal analysis of the HNSCC TME indicated that after Nivolumab therapy, the expression of certain inhibitory immune checkpoints including TIGIT, ENTPD1, and CD276 and LY9, were decreased in Tregs, while LAG-3 showed an increased expression level. The study also found that Tregs had a dense communication network with cluster two, and that certain ligand-receptor pairs, including SPP1/CD44, HLA-E/KLRC2, HLA-E/KLRK1, ANXA1/FPR3, and CXCL9/FCGR2A, had notable changes after the therapy. These changes in gene expression and cell interactions may have implications for the role of Tregs in the TME and in response to Nivolumab therapy.

Non-financial access to healthcare services in rural areas: A case study of people with disabilities living in Northern Iran

by Lida Shams, Tahere Darvish, Mohamad Meskarpour Amiri, Sayyed-Morteza Hosseini-Shokouh, Taha Nasiri

Introduction

Access to healthcare for persons with disabilities (PWDs) is an important but often ignored issue for achieving universal health coverage. The current study aimed to investigate PWDs’ access to healthcare in the rural areas in north of Iran.

Methods

Following a descriptive-analytical design, 471 persons with disabilities (PWDs) living in the Nor city, Mazandaran province, were selected using quota sampling. Data were collected by a valid and reliable questionnaire that contained dimensions of time, geography, physical, and acceptability using face-to-face interviews. The findings are provided by central and dispersion indicators and analyses are performed with linear Regression using SPSS version 17.

Results

PWDs had moderate access to healthcare services in all dimensions. The regression models for access to health services in all four dimensions were significant (p Conclusion

A small percentage of PWDs had high access to health services. Hence, improving their access to healthcare services, particularly in rural and less developed areas, and developing appropriate policies should be the focus of Iranian policy-makers.

Spatial variation and predictors of missing birth preparedness and complication readiness (BPCR) messages in Ethiopia

by Aklilu Habte, Samuel Hailegebreal, Tamirat Melis, Dereje Haile

Background

The Birth Preparedness and Complication Readiness (BPCR) message is one of the prenatal care packages targeted at reducing maternal and neonatal mortality by avoiding unnecessary delays during labor and delivery. There is limited evidence in Ethiopia that has looked at the spatial variation of missing BPCR messages and potential predictors. Hence, this study aimed to identify spatial predictors missing BPCR messages at the national level.

Methods

The study was based on analysis of 2016 Ethiopia Demographic Health Survey data, using a weighted sample of 4771 women. Arc-GIS version 10.7 and SaTScan version 9.6 statistical software were used for the spatial analysis. To explore spatial variation and locate spatial clusters of missing BPCR messages, the Global Moran’s I statistic and Bernoulli-based spatial scan (SaTScan) analysis were carried out, respectively. Hotspot (Getis-OrdGi*) analysis was conducted to identify Hotspots and Cold spotsof missing BPCR messages. Finally, spatial regression were carried out via ordinary least squares and geographically weighted regression to identify predictors of hotspots for missing BPCR messages.

Results

The overall prevalence of missing BPCR messages in Ethiopia was found to be 44.0% (95%CI: 42.6, 45.4%), with significant spatial variation across regions (Moran’s I = 0.218, p-value Conclusion

The level of missing BPCR messages during pregnancy was found to be high in Ethiopia, with significant local variation. As a result, policymakers at the national level and local planners should develop strategies and initiatives that enhance women’s economic capacities, health-seeking behavior, and media exposure. Furthermore, the regional authorities should focus on strategies that promote universal health coverage through enrolling citizens in health insurance schemes.

Comparison of the preconditioning effect of different exercise training modalities on myocardial ischemia-reperfusion injury

by Reihaneh Mohammadkhani, Kamal Ranjbar, Iraj Salehi, Alireza Komaki, Ebrahim Zarrinkalam, Parsa Amiri

The study of exercise preconditioning can develop strategies to prevent cardiovascular diseases and outline the efficient exercise model. However, the exercise type with the most protective effect against ischemia-reperfusion injury is unknown. In this study, we examined the effects of three kinds of exercise preconditioning on myocardial ischemia-reperfusion in adult rats and explored the possible underlying mechanisms. Male Wistar rats subjected to ten weeks of endurance, resistance, and concurrent training underwent ischemia (30 min) and reperfusion (120 min) induction. Then, infarction size, serum levels of the CK-MB, the redox status, and angiogenesis proteins (VEGF, ANGP-1, and ANGP-2) were measured in the cardiac tissue. Results showed that different exercise training modes have the same reduction effects on infarction size, but ischemia-reperfusion-induced CK-MB was lower in response to endurance training and concurrent training. Furthermore, cardiac VEGF levels increased in all three kinds of exercise preconditioning but ischemia-reperfusion-induced ANGP-1 elevated more in endurance training. The cardiac GPX activity was improved significantly through the resistance and concurrent exercise compared to the endurance exercise. In addition, all three exercise preconditioning models decreased MPO levels, and ischemia reperfusion-induced MDA was lower in endurance and resistance training. Overall, these results indicated that cardioprotection of exercise training against ischemia-reperfusion injury depends on the exercise modality. Cardioprotective effects of aerobic, resistance, and concurrent exercises are due to different mechanisms. The preconditioning effects of endurance training are mediated mainly by pervasive angiogenic responses and resistance training through oxidative stress amelioration. The preconditioning effects of concurrent training rely on both angiogenesis and oxidative stress amelioration.

Maternal exposure to SSRIs or SNRIs and the risk of congenital abnormalities in offspring: A systematic review and meta-analysis

by Weiyi Huang, Robin L. Page, Theresa Morris, Susan Ayres, Alva O. Ferdinand, Samiran Sinha

Background

The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.

Methods

A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.

Results

Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56).

Conclusions

SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.

The lived experience of Omani adolescents and young adults with mental illness: A qualitative study

by Omar Al Omari, Gerald Amandu, Samir Al-Adawi, Zubaida Shebani, Ibtisam Al Harthy, Arwa Obeidat, Khloud Al Dameery, Mohammad Al Qadire, Iman Al Hashmi, Abduallh Al Khawldeh, Mohammed ALBashtawy, Maen Aljezawi

There is currently limited knowledge about the firsthand experiences of adolescents and young adults with mental health problems and the meanings they ascribe to these experiences, particularly within Arab countries. This study, therefore, aimed to explore the lived experience of Omani adolescents and young adults with a mental health problem. A sample of 15 participants aged 13–22 diagnosed with a range of mental health problems took part in the study. A qualitative interview guide consisting of open-ended questions was used to allow participants to speak in-depth about their experiences. Using the thematic analysis approach to uncover patterns in the data, three major themes emerged: “living in darkness”, “perilous journey” and “uncertain future”. Results show that the progress of adolescents and young adults with mental health problems is characterized by several challenges; the most significant of which is having insufficient knowledge about their illness, leading to unnecessary delays in their treatment. These findings shed light on the breadth and depth of the experience of adolescents and young adults with mental health problems and lay the groundwork for further examinations. Implications lie in the development of approaches for preventing or mitigating difficulties faced by adolescents and young adults with mental health problems.

Intravenous acetaminophen for postoperative pain in the neonatal intensive care unit: A protocol for a pilot randomized controlled trial (IVA POP)

by Victoria Anne Archer, Samira Samiee-Zafarghandy, Forough Farrokyhar, Daniel Briatico, Luis H. Braga, J. Mark Walton

Background

In neonates, uncontrolled pain and opioid exposure are both correlated with short- and long-term adverse events. Therefore, managing pain using opioid-sparing approaches is critical in neonatal populations. Multimodal pain control offers the opportunity to manage pain while reducing short- and long-term opioid-related adverse events. Intravenous (IV) acetaminophen may represent an appropriate adjunct to opioid-based postoperative pain control regimes. However, no trials assess this drug in patients less than 36 weeks post-conceptual age or weighing less than 1500 g.

Objective

The proposed study aims to determine the feasibility of conducting a randomized control trial to compare IV acetaminophen and fentanyl to a saline placebo and fentanyl for patients admitted to the neonatal intensive care unit (NICU) undergoing major abdominal or thoracic surgery.

Methods and design

This protocol is for a single-centre, external pilot randomized controlled trial (RCT). Infants in the NICU who have undergone major thoracic or abdominal surgery will be enrolled. Sixty participants will undergo 1:1 randomization to receive intravenous acetaminophen and fentanyl or saline placebo and fentanyl. After surgery, IV acetaminophen or placebo will be given routinely for eight days (192 hours). Appropriate dosing will be determined based on the participant’s gestational age. Patients will be followed for eight days after surgery and will undergo a chart review at 90 days. Primarily feasibility outcomes include recruitment rate, follow-up rate, compliance, and blinding index. Secondary clinical outcomes will be collected as well.

Conclusion

This external pilot RCT will assess the feasibility of performing a multicenter RCT comparing IV acetaminophen and fentanyl to a saline placebo and fentanyl in NICU patients following major abdominal and thoracic surgery. The results will inform the design of a multicenter RCT, which will have the appropriate power to determine the efficacy of this treatment.

Trial registration

ClinicalTrials.gov NCT05678244, Registered December 6, 2022.

Anethole attenuates motor dysfunctions, striatal neuronal activity deficiency and blood brain barrier permeability by decreasing striatal α-synuclein and oxidative stress in rotenone-induced Parkinson’s disease of male rats

by Sadegh Moradi Vastegani, Seyed Esmaeil Khoshnam, Samireh Ghafouri, Nima Bakhtiari, Yaghoob Farbood, Alireza Sarkaki

Introduction

Anethole is the main compound of the essential oil of anise and several other plants, which has antioxidant, anti-inflammatory, and neuroprotective properties. Oxidative stress is considered as an important factor in the pathogenesis of PD. In the present study, we aimed to investigate the effects of anethole against rotenone-induced PD.

Methods

Male Wistar rats were randomly divided into six groups. Control group received DMSO + sunflower oil, model group received rotenone (2 mg/kg, s.c, daily for 35 days), positive control group received L-Dopa, and test groups received anethole (62.5, 125, and 250 mg/kg, i.g, daily for 35 days) 1 hour before each rotenone injection. Body weight changes, rotarod test, stride length test, and extracellular single unit recording were performed after treatment. After behavioral test, Brain water content and blood brain barrier (BBB) permeability were evaluated, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), alpha-synuclein and MAO-B were measured in the striatum.

Results

Chronic administration of rotenone induced body weight loss and caused significant dysfunction in locomotor activity, neuronl firing rate, and BBB. Rotenone also decreased SOD activity, increased MDA level, and elevated the expression of alpha-synuclein and MAO-B in the striatum. However, treatment with anethole attenuated body weight loss, motor function, neuronal activity, and BBB function. Furthermore, Anethole treatment attenuated oxidative stress and decreased the expression of alpha-synuclein and MAO-B compared to the rotenone group.

Conclusion

Our results show that through its antioxidant properties, aethole can improve the cellular, molecular and behavioral characteristics of rotenone-induced Parkinson’s disease.

IL-6 serum level, ARDS, and AKI as risk factors for the COVID-19 infection’s mortality in children

by Idham Jaya Ganda, Try Kartika Eka Putri, Syarifuddin Rauf, Amiruddin Laompo, Ninny Meutia Pelupessy, Sitti Aizah Lawang, Nadirah Rasyid Ridha, Bahrul Fikri, Muhammad Nasrum Massi

Introduction

Dysregulated immune responses are developed in Coronavirus disease-2019 (COVID-19) and Interleukin-6 (IL-6) levels are reflecting the severity of the clinical presentation. This study aimed to analyze IL-6 serum level, Acute Respiratory Distress Syndrome (ARDS), and Acute Kidney Injury (AKI) as risk factors for mortality in children with COVID-19.

Methods

This prospective cohort study was conducted on children with COVID-19 infection confirmed by Real Time Polymerase Chain Reaction (RT-PCR) who were admitted to infection center at Dr. Wahidin Sudirohusodo Hospital from September 2021 to September 2022. Subjects were selected using the consecutive sampling method.

Results

A total of 2,060 COVID-19 RT-PCR tests were performed, and 1,065 children were confirmed positive. There were 291 cases that met the inclusion criteria, with 28.52 percent non-survives and 71.48% survives. The risk factors for mortality were IL-6, ARDS, AKI, Prothrombin Time / Activated Partial Thromboplastin Time (PT/aPTT), oxygen saturation, Absolut lymphocyte count (ALC), leukocytes, Length of Stay (LOS), and nutritional status (p80.97 pg/ml with 93% sensitivity and 90% specificity. Area Under Curve was 0.981 (95% CI), 0.960–1.000). A multivariate analysis showed IL-6 levels with OR 18.570 (95% CI 5.320–64.803), ARDS with Odds Ratio (OR) 10.177, (95% Confidence Interval (CI) 1.310–9.040), and AKI with OR 3.220 (95% CI 1.070–10.362). A combination of increased IL-6, ARDS, and AKI can predict a mortality probability as high as 98.3%.

Conclusion

IL-6, ARDS, and AKI are risk factors for mortality in children with COVID-19. IL-6 level was the highest mortality risk factor.

Robust cardiac segmentation corrected with heuristics

by Alan Cervantes-Guzmán, Kyle McPherson, Jimena Olveres, Carlos Francisco Moreno-García, Fabián Torres Robles, Eyad Elyan, Boris Escalante-Ramírez

Cardiovascular diseases related to the right side of the heart, such as Pulmonary Hypertension, are some of the leading causes of death among the Mexican (and worldwide) population. To avoid invasive techniques such as catheterizing the heart, improving the segmenting performance of medical echocardiographic systems can be an option to early detect diseases related to the right-side of the heart. While current medical imaging systems perform well segmenting automatically the left side of the heart, they typically struggle segmenting the right-side cavities. This paper presents a robust cardiac segmentation algorithm based on the popular U-NET architecture capable of accurately segmenting the four cavities with a reduced training dataset. Moreover, we propose two additional steps to improve the quality of the results in our machine learning model, 1) a segmentation algorithm capable of accurately detecting cone shapes (as it has been trained and refined with multiple data sources) and 2) a post-processing step which refines the shape and contours of the segmentation based on heuristics provided by the clinicians. Our results demonstrate that the proposed techniques achieve segmentation accuracy comparable to state-of-the-art methods in datasets commonly used for this practice, as well as in datasets compiled by our medical team. Furthermore, we tested the validity of the post-processing correction step within the same sequence of images and demonstrated its consistency with manual segmentations performed by clinicians.
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