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Two different complement Factor B (Bf) alleles of the orangutan major histocompatibility complex (MHC) are also conserved in chimpanzee and humans showing importance in primate immunity

Mol Biol Rep. 2024 Nov 21;52(1):6. doi: 10.1007/s11033-024-10086-7.

ABSTRACT

BACKGROUND: Major Human Histocompatibility complex (MHC or HLA in humans) has been associated to autoimmune diseases. However, only statistical phenomenological and no pathogenetic description has been reached after decades. This shows that MHC single locus association studies are probably useless for HLA/diseases association. Extended HLA (class I and class II genes) haplotypes should also be studied conjointly with class III or complement alleles (complotypes). Complotypes in humans are defined as alleles belonging to C2, C4 and Bf (Factor B) genes/proteins (class III). Also, the placing of MHC class I and class II genes close together with complement genes from at least birds to humans shows existence of a strong selection to gather conjointly these loci that fight microbes, help self-maintenance and avoid autoimmunity. In this paper we aim to study Bf alleles in primates in order to rise again interest to study the role of Bf alleles together with other MHC genes in their physiopathology and evolution.

METHODS: Orangutan (Pongo pygmaeus, Popy) cell lines RNA from 6 different individuals were retrotranscribed, PCR amplified, cloned and DNA sequenced in order to study Bf alleles.

RESULTS: A Bf allele identical to that found in chimpanzee (Patr-Bf*A01) and human (rs641153) was found in two of the six studied orangutans: Popy-Bf*A01 and Popy-Bf*A02. This polymorphism is placed in Factor B codon 32 that defines BF*S and Bf*F proteins in man and produce Leu instead of Arg (Bf*S) or Gln (Bf*F). In addition, each new orangutan allele present synonymous differences with each other at codon 25: Popy-Bf*A01 shows ACG while Popy-Bf*A02 bears ACA, both codifying for Thr.

CONCLUSIONS: The selection for about 15 million years (time gap of evolutionary appearance between orangutan and hominids) shows the importance of this particular allele conservation in immune and self defense in primates. The complotypes (Bf,C2 and C4 loci) alleles together with other MHC class I and Cass II loci alleles are often transmitted in block to the germinal line: this indicates that all specific alleles from the MHC different loci may work together to accomplish MHC functions. All MHC loci alleles should be studied together to unveil their physiopathology and also maintenance of specific alleles (like the one described in this paper) for so long time in evolution should be further studied in Bf and the other neighbouring complement loci (C2 and C4).

PMID:39570459 | DOI:10.1007/s11033-024-10086-7

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Neural therapy in notalgia paresthetica

Arch Dermatol Res. 2024 Nov 21;317(1):37. doi: 10.1007/s00403-024-03535-7.

ABSTRACT

Notalgia Paresthetica (NP) is a type of chronic sensory neuropathy characterized by localized itching, pain and dysesthesias including numbness, tingling, burning, coldness, hypo- and hyperesthesia. It is frequently underdiagnosed and thus, there is no established standard of care for treatment. The objective of our study was to evaluate the efficacy of neural therapy in patients with NP. Patients aged 30-60 years with a diagnosis of NP for at least 6 months were included in our study. Intralesional and segmental neural therapy was administered to the patients in five sessions, with one-week intervals between each session. Patients were evaluated with numeric rating scale (NRS) for pain, the PainDETECT Questionnaire for neuropathic pain, the Short Form-12 (SF-12) for quality of life and the 5-D Itch Scale for pruritus. A total of 12 patients diagnosed with NP were included in the study. The median age of the patients included in the study was 45 years (33-59). 58.3% (n = 7) of the patients were female and 41.7% (n = 5) were male. The median duration of pain was 24 (6-60) months. Itching was observed in 75% (n = 9) and hypoesthesia was present in 58.3% (n = 7) of the patients. Comparisons were made with assessment scales before and 3 months after treatment. There was a significant difference in the pre-treatment NRS, PainDETECT Questionnaire, physical component of SF-12 and 5-D itch scale scores compared to post-treatment. Neural therapy represents a promising complementary treatment method for the reduction of pain, neuropathic pain, and pruritus in patients with NP. Furthermore, it has been demonstrated to enhance quality of life.

PMID:39570455 | DOI:10.1007/s00403-024-03535-7

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Bi-directional effects between inflammatory molecules and intracranial aneurysm

Neurosurg Rev. 2024 Nov 21;47(1):865. doi: 10.1007/s10143-024-03070-z.

ABSTRACT

INTRODUCTION: Although inflammation is closely associated with the pathogenesis of intracranial aneurysm (IA), detailed causal associations remain unclear. This study aimed to investigate the causality between circulating inflammatory molecules (IMs) and IA.

MATERIALS AND METHODS: The bi-directional Mendelian randomization (MR) analysis was conducted using two genome-wide association studies (GWAS) for inflammatory molecules (IMs) from Finnish and Icelandic populations, as well as GWAS datasets of IA cases and controls of European descent. Colocalization analysis was performed to validate MR associations. Subsequently, Venn analysis was conducted to identify the overlapped causalities.

RESULTS: Integrating the findings from two MR models, RANTES was suggestively associated with IA (Finnish model: inverse variance-weighted odds ratio [ORIVW] (95% confidence interval [95% CI]), 0.86 (0.74-0.99); Icelandic model: 0.80 (0.68-0.94)) and aneurysmal subarachnoid hemorrhage (aSAH) (ORIVW (95% CI): 0.81 (0.68-0.95) and 0.80 (0.66-0.97) in Finnish and Icelandic models). IA and its subtypes were not associated with any of candidate IMs. However, colocalization analysis failed to identify significant evidence of shared genetic instruments between the exposures and outcomes, except for the MCP3-aSAH pair in the Icelandic model.

CONCLUSIONS: No significant causality was identified between IMs and IA or their subtypes. RANTES is potentially associated with IA and aSAH. Further investigation is warranted to explore the role of IMs in IA development.

PMID:39570436 | DOI:10.1007/s10143-024-03070-z

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Risk of biliary diseases in patients with type 2 diabetes or obesity treated with tirzepatide: A meta-analysis

J Diabetes Investig. 2024 Nov 21. doi: 10.1111/jdi.14340. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the risk of biliary diseases in patients with type 2 diabetes mellitus (T2DM) or obesity treated with tirzepatide.

METHODS: Literature searches were performed using the PubMed, Web of Science, Cochrane Library, and CNKI databases until 20 May 2024. Randomized controlled studies (RCTs) investigating the safety of tirzepatide vs placebo/other hypoglycemic drugs in patients with T2DM or obesity were included. The safety outcomes mainly included the incidence of cholelithiasis, pancreatitis, cholecystitis, and gallbladder/biliary diseases. Cochrane Collaboration’s tool for assessing the risk of bias was used to assess the quality of literature. Heterogeneity was evaluated using I2 statistics.

RESULTS: A total of 12 high-quality RCTs (involving 12,351 patients) were included. The results of meta-analysis showed that tirzepatide was associated with gallbladder/biliary diseases (RR = 1.52; 95%CI: 1.17-1.98; I2 = 0%, P = 0.76) and cholelithiasis (RR = 1.67; 95%CI: 1.14-2.44; I2 = 0%, P = 0.95). Subgroup analysis based on the dose of tirzepatide found no dose-response relationship between different doses of tirzepatide and the risk of gallbladder/biliary diseases and cholelithiasis.

CONCLUSIONS: Based on the data currently available, tirzepatide is associated with the development of cholelithiasis in patients. However, the findings from RCTs still need to be further investigated in many post-marketing safety surveillance programs.

PMID:39569606 | DOI:10.1111/jdi.14340

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A novel plate design for rotational guided growth: An experimental study in immature porcine femurs

J Orthop Res. 2024 Nov 21. doi: 10.1002/jor.26019. Online ahead of print.

ABSTRACT

Guided growth for correction of rotational deformities has been reported in several preclinical and clinical studies. Different adverse effects, like growth retardation, articular deformities, and rebound effect have been reported. We have tested a novel plate concept (RotOs PlateTM) intended for the correction of rotational deformities of long bones by guided growth in a porcine model. The plate has sliding screw holes intended to allow for longitudinal growth. Fourteen skeletally immature female pigs were included in the study in a paired design. Mean duration of intervention was 88 days (83-98). CTscans and X-rays were performed at plate insertion and removal. From the CTscans, 3D-models of the left and right femora were made and used for measuring the achieved rotation. Three pigs were excluded for reasons not related to the plate design. The plates rotated as intended in all pigs. In two pigs, there was a cut-out of the proximal screw on the lateral side. Data from these two pigs were included in the results. We observed a mean difference in rotation between the left and right femur of 5.7° in the external direction (CI: 3.7°-7.7°). No statistically significant deformities in the coronal and sagittal plane were observed. The plate worked as intended, that is, the intended rotation was achieved. CLINICAL SIGNIFICANCE: This large animal study shows promising results for the feasibility of the method. It is an important first step in validating the technique and detecting possible adverse effects before clinical studies.

PMID:39569605 | DOI:10.1002/jor.26019

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Cognitive performance, psychiatric comorbidities, and quality of life in pediatric patients with juvenile idiopathic arthritis: a comparative analysis with healthy controls

Child Neuropsychol. 2024 Nov 21:1-19. doi: 10.1080/09297049.2024.2426272. Online ahead of print.

ABSTRACT

This study aimed to assess the extent of cognitive impairment in children and adolescents with Juvenile Idiopathic Arthritis (JIA). While cognitive deficits are recognized in other systemic rheumatic diseases, exploration within the pediatric JIA population remains limited. The investigation utilized a comprehensive approach to examine neuropsychological test performance. A cohort of 160 participants (79 JIA, 81 healthy controls aged 8-17) underwent evaluations using the Pediatric Quality of Life Inventory (PedsQL), Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL), and the computerized neurocognitive test battery Central Nervous System Vital Signs (CNSVS). Children with JIA exhibited statistically significant cognitive deficits across various parameters (p < .05). This was associated with an increased prevalence of lifelong psychiatric illnesses and diminished overall quality of life compared to healthy counterparts (p < .05). Analysis highlighted that specific JIA subtypes, excluding Oligoarthritis, significantly elevated the risk of neurocognitive impairments, emphasizing the impact on various cognitive outcomes (OR range: 3.1-5.1, 95% CI: 1.163-19.980). Additionally, the active disease stage was identified as a specific risk factor, amplifying the likelihood of low executive functions by 4.3 times (OR: 4.363, 95% CI: 1.095-17.378). This study underscores the critical importance of recognizing and addressing neurocognitive impairments in children with JIA. Specific attention to disease subtypes and activity levels is crucial, with the potential for targeted interventions to enhance overall cognitive well-being and quality of life in this vulnerable population.

PMID:39569588 | DOI:10.1080/09297049.2024.2426272

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Disparities in Receipt of Medications for Opioid Use Disorder Before and During the COVID-19 Pandemic in the US Veterans Health Administration

Subst Use Addctn J. 2024 Nov 21:29767342241293334. doi: 10.1177/29767342241293334. Online ahead of print.

ABSTRACT

BACKGROUND: Populations disproportionately impacted by the opioid epidemic are less likely to receive medications for opioid use disorder (MOUD; OUD). The COVID-19 pandemic exacerbated these disparities. We performed an ecological survey of subpopulations to compare differences in MOUD receipt among Veterans with OUD before versus during the pandemic.

METHODS: Using 2 cross-sections of 2 time periods of national Veterans Health Administration electronic health record data, we calculated proportions of Veterans with any MOUD receipt by demographics, Elixhauser comorbidity index, and natural language processing (NLP)-derived substance use and social determinants of health in each time period. We evaluated differences in MOUD receipt before and during the pandemic by patient characteristics using Chi-square and Cohen’s h for effect size.

RESULTS: Among 62 195 patients with OUD before the pandemic, the proportion prescribed MOUD increased from 46.5% before to 47.5% (P = .0003) during the pandemic. Statistically significant increased receipt of MOUD was observed for patients who were ≥55 years, men, White, with Elixhauser comorbidity indices of 2 and ≥5, and with NLP-derived indicators of substance use. There was a decrease that did not achieve statistical significance in MOUD receipt from before to during the pandemic for patients who were women, Black, Latinx, and food insecure.

CONCLUSIONS: The proportions of patients with OUD prescribed MOUD increased from before to during the pandemic. However, Veterans who were women, Black, Latinx, and food insecure did not experience these increases. These patients may benefit from interventions such as targeted outreach efforts to improve MOUD engagement to reduce OUD harms.

PMID:39569566 | DOI:10.1177/29767342241293334

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Relationship between psychological capital and nursing burnout: A systematic review and meta-analysis

Int Nurs Rev. 2024 Nov 21. doi: 10.1111/inr.13072. Online ahead of print.

ABSTRACT

AIM: This systematic review and meta-analysis aimed to analyze studies that examined the relationship between psychological capital and burnout in registered nurses.

BACKGROUND AND INTRODUCTION: Registered nurses are subject to high rates of burnout, with negative consequences on health, well-being, and quality of care. Psychological capital could be an important element in preventing or reducing this condition.

METHODS: This research is based on the Joanna Briggs Institute Guidelines and Preferred Reporting Items for systematic reviews and meta-analysis. A total of 180 studies on psychological capital and burnout were retrieved from Web of Science, Scopus, PubMed, Medline, and PsycINFO. The articles were written in English, Spanish, French, and Portuguese. Then, 23 studies were included in several meta-analyses (random-effects models) performed with the R statistical program.

RESULTS: Analysis of the 23 studies revealed that psychological capital and burnout are significantly correlated. The Psychological Capital Questionnaire (PCQ) and the Maslach Burnout Inventory (MBI) were the most used scales to measure psychological capital and burnout, respectively. The meta-analyses showed an inverse correlation between psychological capital and burnout (r = -0.44, 95% CI [-0.51, -0.36], n = 6092), and emotional exhaustion (r = -0.32, 95% CI [-0.42, -0.21], n = 3349).

CONCLUSION: This review provides evidence of the negative relationship between psychological capital and burnout in registered nurses. Therefore, enhancing psychological capital is an effective strategy to prevent and reduce burnout in nurses.

IMPLICATIONS FOR NURSING AND HEALTH POLICY: Psychological capital is a personal resource open to development over time and susceptible to interventions aimed at promoting optimism, efficacy, hope, and resilience. In that sense, training aimed at improving psychological capital, as a protective mechanism to prevent and reduce burnout and emotional exhaustion, should be considered together with organizational measures to promote nurses’ health and well-being.

PMID:39569557 | DOI:10.1111/inr.13072

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Diffusion-weighted imaging based on intravoxel incoherent motion: correlation with molecular prognostic factors and subtypes in breast cancer

Acta Radiol. 2024 Nov 21:2841851241296029. doi: 10.1177/02841851241296029. Online ahead of print.

ABSTRACT

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), which indicates biological tissue attributes, may be applied to accurately assess breast tumors.

PURPOSE: To analyze the IVIM parameters of different molecular prognostic factors and subtypes to find out whether there are any connections.

MATERIAL AND METHODS: A total of 181 patients enrolled in this retrospective study had preoperative magnetic resonance imaging (MRI) examinations, and pathologies were verified as breast cancers. Regions of interest were placed at all slices of the parameter maps (D, tissue diffusivity; ADC, apparent diffusion coefficient; f, perfusion fraction; and D*, pseudo-diffusivity maps) of IVIM and generated parameter values to be used for comparative analysis among molecular prognostic factors and subtypes.

RESULTS: D and ADC were greater in estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-positive, and Ki67-low expression groups (all P values < 0.05). The progesterone receptor (PR)-negative group had a higher D value (P < 0.05). f was larger in the lymph node metastasis-negative group and the PR-positive group (P = 0.012 and 0.046, respectively). Among breast cancer subtypes, D and ADC were different between the HER2-overexpression and the Luminal B (HER2-negative) subtypes (P = 0.019 and 0.028, respectively). The difference in D between the luminal and non-luminal subtypes was statistically significant (P = 0.008). The triple-negative subtype significantly differs from the other subtypes in D* and f (P = 0.012 and 0.016, respectively).

CONCLUSION: IVIM-related metrics exhibited relationships with breast cancer molecular prognosis factors and subtypes.

PMID:39569544 | DOI:10.1177/02841851241296029

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Two Years Post-COVID-19: An Ecologic Study Evaluating the Impact on Brazil’s Mammographic Screening Program

Cancer Control. 2024 Jan-Dec;31:10732748241303425. doi: 10.1177/10732748241303425.

ABSTRACT

OBJECTIVES: The objective of this study was to assess the impact of the COVID-19 pandemic, after 2 years, on mammographic screening in Brazil evaluating BIRADS® results, breast cancer diagnosis rates, and breast cancer stage.

STUDY DESIGN: This was an ecological observational study based on retrospective data from Brazil’s mammographic screening program from 2015 to 2023.

METHODS: Data were obtained from the national screening database DATASUS – SISCAN (Cancer System Information) and retrieved in March 2024. Inclusion criteria comprised completeness of mammogram data (incomplete records were excluded), female participants aged 50 to 69 years, and mammograms exclusively performed for screening purposes. The study analyzed the number of mammograms conducted during the specified period, focusing on BIRADS® test results.

RESULTS: Out of 23,851,371 mammograms performed between 2015 and 2023, 15,000,628 were included for analysis. A significant reduction of 39.6% in mammograms was observed in 2020 compared to 2019, followed by a 12.6% decrease in 2021. Notably, a substantial rise in BIRADS categories 4 and 5 examinations was seen post-pandemic. Breast cancer staging analysis revealed a shift towards more advanced stages (III and IV) diagnosed post-pandemic, suggesting potential delays in detection and diagnosis.

CONCLUSIONS: In conclusion, the study highlighted significant discrepancies in mammographic screenings and breast cancer diagnosis rates over 9 years. The pandemic reflected significant influence on the timing and stage at diagnosis, suggesting potential delays in detection and diagnosis that resulted in later identification of more advanced disease stages.

PMID:39569512 | DOI:10.1177/10732748241303425