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Nevin Manimala Statistics

Genetically predicted metabolite mediates the causal relationship between immune cells and autoimmune diseases

Arthritis Res Ther. 2024 Dec 2;26(1):207. doi: 10.1186/s13075-024-03445-z.

ABSTRACT

BACKGROUND: This study investigates the causal role of metabolites mediating immune cells in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) through a Mendelian randomization (MR) study.

METHODS: The two-sample and two-step MR methods were used for the current analysis: (1) causal effects of immune cells on RA and AS; (2) mediation effects of metabolites. Inverse variance weighted (IVW) is the main method to analyze causality, and MR results are verified by several sensitive analyses.

RESULTS: This study first identified the immune cells and metabolites that are causally associated with RA and AS, respectively. Subsequent mediation analyses revealed that of the 61 metabolic factors that were causally associated with RA, 6 were identified as mediators of the relationship between immune cells and RA, including 4-cholesten-3-one levels (mediation ratio: 8.91%), N-lactoyl isoleucine levels (13%), 3- phosphoglycerate to glycerate ratio (12.9%, 2.31%, respectively), Gamma-glutamyl histidine levels (9.54%), and Citrulline to phosphate ratio (15.6%). Among the 52 metabolic factors that were causally associated with AS, 2 were identified as mediators of the relationship between immune cells and AS, including salicylate levels (10.4%) and Glucose to N-palmitoyl-sphingosine (d18:1 to 16:0) ratio (8.72%). These results performed well in sensitivity analysis.

CONCLUSIONS: Genetic predictions show causal relationships between immune cells and autoimmune diseases, and that these causal relationships can be mediated by certain metabolites as mediators.

PMID:39623398 | DOI:10.1186/s13075-024-03445-z

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En bloc resection of the ligamentum flavum for bilateral decompression in unilateral biportal endoscopic transforaminal lumbar interbody fusion: a 2-year follow-up study

J Orthop Surg Res. 2024 Dec 3;19(1):815. doi: 10.1186/s13018-024-05317-3.

ABSTRACT

BACKGROUND: Unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) is a minimally invasive procedure for treating lumbar degenerative diseases. However, the use of endoscopic lumbar interbody fusion does not completely eliminate the risk of dural and nerve root injuries. This study has refined UBE-TLIF to incorporate en bloc resection of the ligamentum flavum for bilateral decompression and aim to detail the surgical procedure and evaluate the clinical outcomes of this modification.

METHODS: This study analyzes the outcomes of 109 consecutive patients treated by a single surgeon for lumbar degenerative disease using UBE-TLIF. Patients were divided into two groups: Group A (51 patients) underwent en bloc resection of the ligamentum flavum, while Group B (58 patients) underwent routine piecemeal resection. Assessed outcomes included surgery-related complications, operation time, estimated blood loss, postoperative stay, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). The surgical technique is detailed within the study.

RESULTS: In Group A, no nerve root or dura injuries were observed, whereas Group B reported one case of nerve root injury and three dura tears. The average operation time for Group A was shorter than that for Group B; however, the difference was not statistically significant (P > 0.05). No significant differences were found in the VAS score, ODI, estimated blood loss, or postoperative stay between the groups during follow-up.

CONCLUSIONS: En bloc resection of the ligamentum flavum for bilateral decompression in UBE-TLIF demonstrates satisfactory clinical outcomes and low perioperative complications rates, offering a safe and innovative alternative for the treatment of lumbar degenerative disease.

PMID:39623387 | DOI:10.1186/s13018-024-05317-3

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Nevin Manimala Statistics

Identification of critical residues at the C-terminal tip of ACKR4 regulating chemokine internalization and βarrestin involvement

Cell Commun Signal. 2024 Dec 2;22(1):576. doi: 10.1186/s12964-024-01961-8.

ABSTRACT

BACKGROUND: Atypical chemokine receptors (ACKRs) play an important role in regulating the availability of chemokines and are responsible for the formation of chemokine gradients required for the directed migration of immune cells in health and disease. ACKR4 shapes gradients of the chemokines CCL19 and CCL21, which are essential for guiding leukocyte homing to lymphoid organs where they initiate an adaptive immune response against invading pathogens. How ACKRs internalize and scavenge chemokines on the molecular level remains poorly understood. Current state-of the art methods to study βarrestin recruitment, signaling and trafficking of ACKRs – and G-protein-coupled receptors in general – rely heavily on C-terminally tagged receptors with unknown consequences for receptor functions.

METHODS: Fluorescently labelled CCL19 was used to quantify chemokine internalization by native and tagged receptors as assessed by flow cytometry and live cell confocal microscopy. Steady-state interaction and chemokine-driven recruitment of βarrestins was determined by NanoBiT bystander assays. βarrestin-dependency for CCL19 internalization was determined in wild-type versus βarrestin1/2-double deficient cell lines. Statistical significance was determined by unpaired t-test or one-way ANOVA with Dunnett’s or Tukey’s multiple comparison tests.

RESULTS: Addition of a C-terminal tag selectively affected the function of ACKR4, but not other ACKRs. Fusing a short peptide tag or a fluorescent protein to ACKR4 significantly augmented its ability to internalize its cognate ligand CCL19. In comparison to native ACKR4, its C-terminal tagging provoked an elevated pre-association of βarrestins with the plasma membrane, yet a reduction in chemokine-driven βarrestin recruitment. Furthermore, the addition of a C-terminal tag led to a shift from a βarrestin-dependent towards a βarrestin-independent endocytosis pathway. Similar results on chemokine uptake and on βarrestin-dependency were obtained with ACKR4 variants, in which a putative class II PDZ-binding domain located at the C-terminal tip of the receptor was mutated.

CONCLUSION: This study identifies that the integrity of the C-terminus of ACKR4 is critical for receptor function. The addition of a C-terminal tag to ACKR4 enhances chemokine uptake and alters the involvement of βarrestins in receptor trafficking.

PMID:39623381 | DOI:10.1186/s12964-024-01961-8

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Nevin Manimala Statistics

Measuring domestic violence against Egyptian women and its consequent cost using a latent variable model

BMC Womens Health. 2024 Dec 2;24(1):634. doi: 10.1186/s12905-024-03465-6.

ABSTRACT

BACKGROUND: Domestic Violence is a threatening worldwide problem. Its consequences against women can be dramatic, as it negatively affects women’s quality of life reflected in their general wellbeing including physical, mental, emotional and sexual health, in addition to the economic cost. Both domestic violence and its cost are multidimensional constructs that cannot be directly measured.

METHODOLOGY: In this study, a latent trait model is used by applying item response theory to measure both domestic violence and its consequent cost via thirty-five observed variables. Accordingly, the study fills a gap in the literature since it is the first attempt to examine the relationship between domestic violence and its consequent cost in Egypt using latent variable modelling rather than simple descriptive statistics. Each construct is considered as a multidimensional latent variable. The overall latent trait model also estimates the relationship between domestic violence and its consequent cost. The effect of a number of socioeconomic covariates on domestic violence is examined within the model. The proposed model is fitted to data from the 2015 Egypt Economic Cost of Gender-Based Violence Survey (ECGBVS) using Mplus software.

RESULTS: The study shows that psychological violence is equally important in measuring domestic violence, as physical violence. The cost resulting from domestic violence relies in its measurement both on the reduced quality of life and the monetary cost endured by the violated woman and children. For socioeconomic covariates, it is shown that domestic violence is affected by women’s and husband’s age, educational level, and husband’s occupational status.

CONCLUSION: Domestic violence is measured by summarizing four forms of violence: physical, psychological, sexual and economic violence, in a single continuous latent variable measuring “Domestic Violence”. Similarly, Cost is measured by summarizing three forms of consequent cost of violence: economic cost, cost on children and cost on women’s quality of life, in another a single continuous latent variable “Cost”. Each of these dimensions is measured by a number of aspects, reflecting the multidimensional nature of the variables. The fitted latent trait model ensured the positive relationship between Domestic Violence and its consequent multidimensional cost.

PMID:39623376 | DOI:10.1186/s12905-024-03465-6

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The accuracy of anatomic landmarks on the occlusal plane: a comparative study between conventional and 3D image method

BMC Oral Health. 2024 Dec 2;24(1):1459. doi: 10.1186/s12903-024-05132-6.

ABSTRACT

BACKGROUND: To establish the occlusal plane, the conventional methods for facial analysis to gain accurate alignment of the occlusal plane are inadequate, while 3D technologies are an ideal diagnostic tool. The aims of this research are to compare the difference accuracy of anatomic landmarks on the occlusal plane and ala-tragus line between the conventional clinical method and 3D image method in both non-orthodontic and orthodontic treatment volunteers.

METHODS: A total of 44 volunteers (22 non-orthodontic and 22 orthodontic treatment volunteers) with normal occlusion were selected. All volunteers received 2 operative methods for occlusal plane determination. In conventional method, the occlusal plane was defined by the fox plane line. The ala-tragus line was defined by the radio-opaque markers. In the 3D image method, the volunteers were recorded intraoral images, 3D facial images and CBCT images. A 3D virtual picture was created using EXOCAD® software. The occlusal plane was generated by the incisal and occlusal surfaces of the teeth. Both methods, the angles and distances between the occlusal plane and ala-tragus line were measured and compared statistically on both sides of each volunteer.

RESULTS: Both volunteers’ group, the mean angles and distances between the occlusal plane-ala tragus line in the conventional method were reported to be significantly greater than the 3D method (P < 0.05). The percentage difference of angles in conventional method were reported to be significantly higher by 13.61-21.58% (p < 0.05) compared to the 3D method. The percentage difference of distances in the conventional method were reported to be significantly greater than the 3D method by 4.73-7.51% (p < 0.05).

CONCLUSIONS: Within the limitation of the study, it can be concluded that both conventional and digital methods for establishing the occlusal plane are not parallel to the occlusal plane. The occlusal plane and ala-tragus line in the conventional method and the 3D method were significantly different in terms of angles and distances in both non-orthodontic and orthodontic treatment volunteers. However, the deviation angle of both methods is approximately 13-20 degrees, which is clinically acceptable for occlusal plane establishment. The accuracy of both methods is still within the using in clinical implementation.

PMID:39623366 | DOI:10.1186/s12903-024-05132-6

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Plasmodium Falciparum and mosquito vector IgG patterns across suspected malaria cases in Ghana

BMC Infect Dis. 2024 Dec 2;24(1):1374. doi: 10.1186/s12879-024-10248-9.

ABSTRACT

INTRODUCTION: Malaria, a widespread tropical disease, remains a significant global health issue, resulting in numerous deaths each year. In Ghana, malaria is a leading cause of illness, contributing to a large proportion of hospital outpatient visits. The study assessed the pattern of malaria and vector IgG antibody levels among suspected malaria patients seeking healthcare at selected health facilities across Ghana.

METHODS: Samples from a total of 823 participants aged 1 to 85 years with clinical malaria from the ten regions of Ghana were recruited into the study. Archived plasma obtained from each participant was used to assess antibody responses against MSP1 (19 k), MSP2 (FC27 & 3D7), MSP3, gSG6-P1, and GLURP-RO using ELISA. The data were categorized according to study site, age group, gender, and diagnostic tests. Data were analyzed using Kruskal-Wallis’s statistics. The statistical significance was assessed at 0.05.

RESULTS: The mean ± standard error of the mean (S.E) of MSP3 IgG concentration for the different age groups were 16, 847 ± 3, 031 ng/mL for 0-4 years, 18, 973 ± 4,357 ng/mL for 5-10 years, 25,961 ± 5,436 ng/mL for 11-15 years and 76, 244 ± 8, 209 ng/mL for ≥ 16 years. A significant (Kruskal-Wallis statistic = 122.6, p < 0.0001) increase in P. falciparum MSP 3 (p < 0.0001) and gSG6-P1(p < 0.0001) IgG concentration was observed with increasing age categories. There were significant differences in antibody responses against MSP2 (FC27) IgG (Kruskal-Wallis statistic = 29.63, p = 0.0005), MSP3 IgG (Kruskal-Wallis statistic = 32.53, p = 0.0002), GLURP-RO IgG (Kruskal-Wallis statistic = 52.8, p < 0.0001) and gSG6-P1 IgG (Kruskal-Wallis statistic = 152.8, p < 0.0001) across the study regions.

CONCLUSION: The study reveals that IgG against merozoite surface proteins MSP3, GLURP-RO, and gSG6-P1 but not MSP1 and MSP2 antibodies increase with age. The mean IgG antibody concentrations varied in the selected regions of Ghana. A longitudinal study where confounding factors are controlled for is recommended to provide insights into the development of immunity and antibody efficacy, and to enhance the effectiveness of malaria prevention efforts in Ghana. This will help improve the overall understanding of malaria transmission.

PMID:39623362 | DOI:10.1186/s12879-024-10248-9

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Live attenuated goatpox vaccination in pregnant Murcia-Granada goats: dosage implications and outcomes

BMC Vet Res. 2024 Dec 2;20(1):544. doi: 10.1186/s12917-024-04395-z.

ABSTRACT

BACKGROUND: Infectious diseases, particularly the Goatpox virus (GTPV) from the Poxviridae family, significantly impact livestock health and agricultural economies, especially in developing regions. Recent GTPV outbreaks in previously eradicated areas underscore the need for effective control measures, with vaccination being the most reliable strategy. This study investigates the effects of administering standard and double doses of live attenuated goatpox vaccine in pregnant Murcia-Granada goats, a non-native breed in Iran, to determine optimal vaccination protocols.

RESULTS: In 2018, 400 healthy and pregnant Murcia Granada goats imported from Spain were divided into groups of 200 and vaccinated with either a standard dose (0.5 ml) or a double dose (single 0.9 ml injection) of live attenuated goatpox vaccine. Post-vaccination, the goats were monitored daily for clinical signs of infection, with samples collected for PCR analysis to detect the presence of GTPV strains. In group A, which received the standard vaccine dose, no abortions or vaccine-related side effects were observed, and body temperatures remained normal. In group B, administered a double dose, 37% of the goats experienced abortions, displaying signs of GTPV infection, such as skin lesions (pox lesions) and increased body temperatures. Molecular analysis confirmed the vaccine strain of GTPV as the infection source, ruling out external contamination. Statistical analysis showed no significant differences in abortion rates concerning gestational age or t he age of the pregnant goats.

CONCLUSION: The study highlights the importance of adhering to standard vaccine dosages in pregnant Murcia Granada goats to prevent adverse outcomes like abortions. This study emphasizes the necessity to review and revise vaccination protocols tailored to specific breeds and varying maintenance conditions, including pregnancy and outbreak scenarios. These findings stress the necessity for cautious and tailored vaccination strategies to ensure the safety and efficacy of vaccines in different goat breeds.

PMID:39623355 | DOI:10.1186/s12917-024-04395-z

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Información es poder (information is power): menopause knowledge, attitudes, and experiences in midlife Hispanic women and Latinas

BMC Womens Health. 2024 Dec 2;24(1):633. doi: 10.1186/s12905-024-03434-z.

ABSTRACT

BACKGROUND: Latinas constitute nearly 20% of midlife women in the United States (U.S.), but remain underrepresented in menopause research. Many midlife Latinas are disadvantaged by limited English proficiency, less formal education, living below the federal poverty level, lack of health insurance, and social isolation and discrimination – factors that negatively affect menopause-related symptoms and health outcomes. This study aimed to understand knowledge, attitudes, and experiences of the menopause transition among midlife Latinas.

METHODS: We conducted a qualitative descriptive study using five focus groups with 29 Hispanic/Latina midlife women. An emergent content analysis was performed by four bilingual coders. Data on socio-demographics, menopausal symptoms, menopause knowledge, and attitudes toward menopause and hormone therapy were collected over the phone. Descriptive statistics were performed to characterize study participants.

RESULTS: Participants were aged 50.3 ± 6.3 years, 45% postmenopausal, 79% viewed menopause positively, and 55% reported having “little knowledge” about menopause. Seven themes emerged: 1) menopause is a stage of life (una etapa de vida); 2) not wanting to become an old lady (no quererme hacer viejita); 3) in our culture, we do not ask [about menopause]; 4) family dynamics; 5) each body is different (todo cuerpo es diferente); 6) menopause self-management and treatment options; 7) information is power (información es poder).

CONCLUSIONS: Although Latinas reported having a positive view of menopause, we found a need for culturally-tailored comprehensive menopause education. The importance of involving family members in menopause education was also revealed. Our next steps are to determine the best menopause messaging strategies and educational formats for midlife Latinas.

PMID:39623354 | DOI:10.1186/s12905-024-03434-z

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Differences in brain spindle density during sleep between patients with and without type 2 diabetes

Comput Biol Med. 2024 Dec 1;184:109484. doi: 10.1016/j.compbiomed.2024.109484. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep spindles may be implicated in sensing and regulation of peripheral glucose. Whether spindle density in patients with type 2 diabetes mellitus (T2DM) differs from that of healthy subjects is unknown.

METHODS: Our retrospective analysis of polysomnography (PSG) studies identified 952 patients with T2DM and 952 sex-, age- and BMI-matched control subjects. We extracted spindles from PSG electroencephalograms and used rank-based statistical methods to test for differences between subjects with and without diabetes. We also explored potential modifiers of spindle density differences. We replicated our analysis on independent data from the Sleep Heart Health Study.

RESULTS: We found that patients with T2DM exhibited about half the spindle density during sleep as matched controls (P < 0.0001). The replication dataset showed similar trends. The patient-minus-control paired difference in spindle density for pairs where the patient had major complications were larger than corresponding paired differences in pairs where the patient lacked major complications, despite both patient groups having significantly lower spindle density compared to their respective control subjects. Patients with a prescription for a glucagon-like peptide 1 receptor agonist had significantly higher spindle density than those without one (P ≤ 0.03). Spindle density in patients with T2DM monotonically decreased as their highest recorded HbA1C level increased (P ≤ 0.003).

CONCLUSIONS: T2DM patients had significantly lower spindle density than control subjects; the size of that difference was correlated with markers of disease severity (complications and glycemic control). These findings expand our understanding of the relationships between sleep and glucose regulation.

PMID:39622099 | DOI:10.1016/j.compbiomed.2024.109484

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Epidemiology of elderly burn patients in the United States: Mortality patterns and risk factors revealed by CDC WONDER database

Burns. 2024 Nov 9;51(1):107311. doi: 10.1016/j.burns.2024.107311. Online ahead of print.

ABSTRACT

INTRODUCTION: Burn-related fatalities pose a significant global public health challenge, with a substantial impact on the elderly population. This study examines two decades of burn-related mortality data in the United States, aiming to understand the trends, disparities, and contributing factors among adults aged 65 and older.

OBJECTIVES: The primary objectives of this study are to (1) analyze the trends in burn-related mortality rates among older adults, (2) investigate disparities based on gender, race and geographic regions, and (3) identify comorbidities and complications associated with burn-related deaths in this demographic.

METHODS: Data were obtained from the Centers for Disease Control and Prevention (CDC) using the National Center for Health Statistics database. The study cohort consists of individuals aged 65 and older who experienced burn-related deaths between 1999 and 2020. Various demographic variables, including age, sex, race/ethnicity, and location of death, were considered. The study also examined urban-rural classifications and regional differences. Mortality rates were calculated and adjusted for age. Joinpoint regression analysis was employed to assess trends in age-adjusted mortality rates over time. Modes of death and common comorbidities and complications were analyzed.

RESULTS: Between 1999 and 2020, a total of 96,498 older adults succumbed to burn injuries in the United States. Analysis revealed a concerning increase in burn-related mortality rates from 2012 onwards. Demographic disparities were evident, with older men consistently exhibiting higher mortality rates compared to women. Racial disparities were observed, with Black individuals experiencing the highest mortality burden. Geographic analysis indicated elevated mortality rates in Western states and rural areas. Accidents emerged as the leading cause of death, with ischemic heart disease and hypertensive diseases being prevalent comorbidities. Complications, with septicemia being the most common, contribute significantly to mortality.

CONCLUSION: Our analysis of 20 years of burn-related mortality data from the CDC reveals alarming trends in the United States. Unlike global trends, mortality rates have stagnated from 1999 to 2020, indicating a persistent public health challenge. Black individuals aged over 65 bear the brunt of burn-related mortality, facing the highest age-adjusted rates among all racial groups. Regional disparities are stark, with states in the top 90 % exhibiting significantly higher age-adjusted mortality rates compared to those in the bottom 10 %. Moreover, rural areas consistently report higher mortality rates than urban areas. Ischemic heart disease, hypertensive diseases, and other heart-related conditions emerge as prevalent comorbidities. To effectively reduce burn-related injuries and fatalities, targeted public health policies are imperative. These interventions must prioritize high-risk populations and adopt culturally sensitive approaches to promote safety. Additionally, enhancing access to healthcare and fire safety education is vital for mitigating the burden of burn-related mortality among the elderly population.

PMID:39622090 | DOI:10.1016/j.burns.2024.107311