Determining the association between systematic lupus erythematosus and the occurrence of primary biliary cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Autoimmune diseases often coexist; however, the concomitant occurrence of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) is rare. Therefore, this study aims to provide a comprehensive summary of evidence regarding the co-occurrence of SLE and PBC. METHODS: PubMed, Web of Science, ScienceDirect, and Google Scholar databases were systematically and comprehensively searched for records published up to February 2024. Full-text articles that aligned with the study's aim were included, while those published in languages other than English and those designed as case reports, reviews, conference abstracts, or editorials were excluded. Statistical analyses were performed using Comprehensive Meta-Analysis software, and methodological quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Only 14 studies that met the inclusion criteria with 3944 PBC and 9414 SLE patients were included for review and analysis. Pooled data analysis revealed that approximately 1.1% of SLE patients have concomitant PBC (range: 0.02-7.5%), while around 2.7% of PBC patients concurrently have SLE (range: 1.3-7.5%). Furthermore, qualitative data analysis indicated that the prevalence of PBC in SLE patients presenting with hepatic dysfunction or abnormal liver enzymes ranges from 2 to 7.5%. CONCLUSION: Although the concomitant occurrence of SLE and PBC is rare, the small proportion of patients where these diseases coexist warrants close monitoring by clinicians. This underscores the importance of surveillance to prevent their co-occurrence.

Treatment with Antihistamines and the Risk of Liver Cancer in Patients with Viral Hepatitis: A Multi-Center Cohort Study.

Background: The effects of antihistamines on cancer risk and prognosis have been inconsistent across cancers. The aim of this multi-center cohort study was to investigate the association between antihistamine use and the risk of liver cancer in individuals with viral hepatitis. Methods: This multi-center cohort study included individuals diagnosed with hepatitis B or hepatitis C between January 2008 and March 2022. For antihistamine-treated patients, the index date was the date of antihistamine prescription, and for non-users, it was the date of hepatitis diagnosis. Participants were followed for five years, with the primary outcome of interest being new-onset liver cancer. The incidence rate and the adjusted hazard ratio (aHR) along with its 95% confidence interval (CI) of the outcome were calculated. Subgroup analyses were conducted, stratified by types of viral hepatitis including hepatitis C and hepatitis B. An additional validation study was performed. Results: The study included a total of 7748 patients with viral hepatitis. The incidence rate was 12.58 per 1000 person-years in patients with viral hepatitis on antihistamines, compared to 3.88 per 1000 person-years in those without antihistamine use. After adjusting for factors including age, sex, body mass index (BMI), comorbidities, laboratory data of liver function tests, comedications, and the use of antiviral therapies, the risk of new-onset liver cancer was significantly higher in patients on antihistamines (aHR = 1.83, 95% CI, 1.28-2.60). In patients with hepatitis C, the incidence rate in the antihistamine group was 15.73 per 1000 person-years, while non-users had a rate of 4.79 per 1000 person-years. Patients with hepatitis C on antihistamines had a significantly higher risk of developing liver cancer (aHR = 3.24, 95% CI, 2.16-4.86). Conclusions: This multi-center cohort study reported an increased risk of liver cancer in patients with hepatitis B or hepatitis C treated with antihistamines. Long-term follow-up studies are warranted to validate the findings.

Safety and efficacy of liposomal irinotecan as the second-line treatment for advanced pancreatic cancer: A systematic review and meta-analysis.

INTRODUCTION: The use of nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and increased area under the concentration-time curve. However, comprehensive systematic reviews or meta-analyses evaluating its efficacy as a second-line treatment have been scarce. Therefore, this study aims to review the current body of evidence on nal-IRI, assessing its overall clinical performances regarding the disease. METHODS: A systemic literature search was conducted based on articles published before September 26, 2023 in PubMed, Cochrane Library, EMBASE, and Web of Science databases. The fixed effect model was performed to calculate pooled mean difference and odds ratio for essential outcomes, such as overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events. RESULTS: A total of 21 studies, including 3017 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, together with 5-fluorouracil and leucovorin, resulted in significantly improved PFS and OS, with a pooled mean difference of 1.01 months (95% confidence interval (95%CI)=0.97-1.05, p<0.01) and 0.29 months (95% CI=0.18-0.39, p<0.01) respectively; a pooled risk ratio of 2.06 (95%CI=1.30-3.27, p=0.002) for ORR compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted. CONCLUSION: Nal-IRI-based second-line treatments exhibited significantly improved PFS, OS and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.

Tooth Loss and Chronic Pain: A Population-based Analysis of the National Health and Nutrition Examination Survey.

Poor oral health conditions in adults are associated with chronic pain. A nationwide cross-sectional study was conducted to investigate the link between tooth loss and chronic pain. The study involved 8,662 participants from the National Health and Nutrition Examination Survey. Tooth count was categorized into 4 groups, and chronic pain was defined as persistent pain lasting over 3 months despite treatment. Location of the chronic pain, demographics, comorbidities, lifestyle determinants, and dietary intake were retrieved. Univariate and multivariate logistic regression were used to explore cross-sectional associations between tooth count and chronic pain. Compared to participants with more than 20 teeth, those with severe tooth loss presented greater odds of chronic pain (adjusted odds ratio [aOR] = 2.111, 95% confidence intervals (CI) = 1.213-3.676 for patients with 1-8 teeth). Edentulous participants presented with significantly higher odds of chronic pain in the lower extremities (78.4%) and buttocks (49.5%). In the multivariate model, apart from rheumatic arthritis (aOR = 4.004, 95% CI = 2.766-5.798), variables of higher chronic pain included smoking (aOR = 1.518, 95% CI = 1.228-1.878), and hypertension (aOR = 1.463, 95% CI = 1.013-2.112). On the contrary, being Mexican American (aOR = .603, 95% CI = .414-.880) was associated with lower odds of chronic pain. The findings suggested a significant link between chronic pain and tooth loss, independent of ethnicity, lifestyle determinants, and immune-mediated inflammatory diseases including rheumatoid arthritis. PERSPECTIVE: A U.S. nationwide study examined tooth loss and chronic pain. Those with severe tooth loss had increased odds of chronic pain. Edentulous individuals presented higher odds of pain in lower extremities and buttocks. This study highlighted the link between tooth loss and chronic pain, independent of comorbidities and lifestyle factors.

Fast and furious: pregnancy outcome with one-step rehydration in the warming protocol for human blastocysts.

RESEARCH QUESTION: Do embryos warmed using a one-step rehydration protocol with a more efficient workflow result in comparable pregnancy rates to the standard multi-step rehydration protocol? DESIGN: A retrospective cohort study of 3439 frozen embryo transfers (FET). Clinical outcomes of 833 FETs using a one-step rehydration protocol were reviewed and compared with results from the control group (2606 FETs using standard multi-step rehydration protocol). Primary outcome was ongoing pregnancy rate. Secondary outcomes were survival, positive pregnancy, clinical pregnancy, implantation and miscarriage rates. RESULTS: Survival rates were identical between the two groups (99.5%). Clinical pregnancy rate was 63.0% in the one-step warming protocol, comparable to 59.9% in the multi-step rehydration protocol. A significant increase was observed in the ongoing pregnancy rate with 60.4% in the one-step rehydration versus 55.4% in the multi-step rehydration group (P = 0.011); implantation rate was 63.6% versus 57.0% (P = 0.0005). The miscarriage rate of 4.0% in the one-step rehydration protocol was significantly lower compared with 7.6% in the multi-step rehydration protocol (P = 0.0001). Comparable outcomes persisted even when the analysis was extended to embryos that had and had not undergone preimplantation genetic testing (PGT), as well as day of development of the blastocysts. When controlling for variables of age, PGT, blastocyst development day and embryo expansion, rapid warming significantly increased chances of an ongoing pregnancy (adjusted OR 1.264, 95% CI 1.076 to 1.484). CONCLUSION: A one-step rehydration protocol resulted in identical survival rates and improved ongoing pregnancy rates compared with the multi-step rehydration technique.

Are isolated ocular motor nerve palsies in the elderly truly 'low risk' for abnormal neuro-imaging outcomes?

BACKGROUND: Neurologically isolated ocular motor nerve palsies often present a management dilemma. Neuroimaging is more likely to be offered to patients <50 years without coexisting ischaemic risk factors as their risk of sinister underlying causes is thought to be higher. However, populations are rapidly ageing and advanced neuroimaging is now more widely available. We thus investigated the incidence of abnormal neuroimaging outcomes in the traditionally low-risk older patient group. METHODS: This is a retrospective cohort study of 353 patients presenting with isolated ocular motor nerve palsies to a tertiary neuro-ophthalmology service in Singapore over a four-year (2015 to 2019) period. Clinical data was obtained through manual review of case records. Common aetiologies, age-based differences in prevalence of causes and abnormal neuroimaging outcomes were statistically analysed. RESULTS: Abnormal neuroimaging outcomes were significantly greater in the younger cohort only when age segregation was performed at 60 years of age. In a multivariate analysis, acute onset rather than ischaemic risk factors were independently predictive of normal neuroimaging outcomes. After adjusting for prior cancer risk and clinical bias from presumed ischaemic palsies, abnormal neuroimaging outcomes were seen in 14.1% ≥ 50 yrs, 10.9% ≥ 60 yrs and 15.1% ≥ 70 yrs. CONCLUSIONS: In patients presenting with isolated ocular motor nerve palsies, acute onset may be a more reliable indicator of an ischaemic palsy rather than advanced age or presence of ischaemic risk factors. If onset is not acute, neuroimaging should be considered irrespective of age and coexisting ischaemic risk factors.

PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.

Purinosomes serve as metabolons to enhance de novo purine synthesis (DNPS) efficiency through compartmentalizing DNPS enzymes during stressed conditions. However, the mechanism underpinning purinosome assembly and its pathophysiological functions remains elusive. Here, we show that K6-polyubiquitination of the DNPS enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) by cullin-5/ankyrin repeat and SOCS box containing 11 (Cul5/ASB11)-based ubiquitin ligase plays a driving role in purinosome assembly. Upon several purinosome-inducing cues, ASB11 is upregulated by relieving the H3K9me3/HP1α-mediated transcriptional silencing, thus stimulating PAICS polyubiquitination. The polyubiquitinated PAICS recruits ubiquitin-associated protein 2 (UBAP2), a ubiquitin-binding protein with multiple stretches of intrinsically disordered regions, thereby inducing phase separation to trigger purinosome assembly for enhancing DNPS pathway flux. In human melanoma, ASB11 is highly expressed to facilitate a constitutive purinosome formation to which melanoma cells are addicted for supporting their proliferation, viability, and tumorigenesis in a xenograft model. Our study identifies a driving mechanism for purinosome assembly in response to cellular stresses and uncovers the impact of purinosome formation on human malignancies.

TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation.

Activation of tumor-intrinsic innate immunity has been a major strategy for improving immunotherapy. Previously, we reported an autophagy-promoting function of the deubiquitinating enzyme TRABID. Here, we identify a critical role of TRABID in suppressing anti-tumor immunity. Mechanistically, TRABID is upregulated in mitosis and governs mitotic cell division by removing K29-linked polyubiquitin chain from Aurora B and Survivin, thereby stabilizing the entire chromosomal passenger complex. TRABID inhibition causes micronuclei through a combinatory defect in mitosis and autophagy and protects cGAS from autophagic degradation, thereby activating the cGAS/STING innate immunity pathway. Genetic or pharmacological inhibition of TRABID promotes anti-tumor immune surveillance and sensitizes tumors to anti-PD-1 therapy in preclinical cancer models in male mice. Clinically, TRABID expression in most solid cancer types correlates inversely with an interferon signature and infiltration of anti-tumor immune cells. Our study identifies a suppressive role of tumor-intrinsic TRABID in anti-tumor immunity and highlights TRABID as a promising target for sensitizing solid tumors to immunotherapy.

Outcomes of decompressive craniectomy for large territory cerebral infarction with and without prior reperfusion: a multicentre retrospective review.

PURPOSE: Reperfusion therapy has greatly improved outcomes of ischaemic stroke but remains associated with haemorrhagic conversion and early deterioration in a significant proportion of patients. Outcomes in terms of function and mortality are mixed and the evidence for decompressive craniectomies (DC) in this context remains sparse. We aim to investigate the clinical efficacy of DC in this group of patients compared to those without prior reperfusion therapy. METHODS: A multicentre retrospective study was conducted between 2005 and 2020, and all patients with DC for large territory infarctions were included. Outcomes in terms of inpatient and long-term modified Rankin scale (mRS) and mortality were assessed at various time points and compared using both univariable and multivariable analyses. Favourable mRS was defined as 0-3. RESULTS: There were 152 patients included in the final analysis. The cohort had a mean age of 57.5 years and median Charlson comorbidity index of 2. The proportion of preoperative anisocoria was 15.1%, median preoperative Glasgow coma scale was 9, the ratio of left-sided stroke was 40.1%, and ICA infarction was 42.8%. There were 79 patients with prior reperfusion and 73 patients without. After multivariable analysis, the proportion of favourable 6-month mRS (reperfusion, 8.2%; no reperfusion, 5.4%) and 1-year mortality (reperfusion, 26.7%; no reperfusion, 27.3%) were similar in both groups. Subgroup analysis of thrombolysis and/or thrombectomy against no reperfusion was also unremarkable. CONCLUSION: Reperfusion therapy prior to DC performed for large territory cerebral infarctions does not affect the functional outcome and mortality in a well-selected patient population.

Supplementation of Lactobacillus plantarum (TCI227) Prevented Potassium-Oxonate-Induced Hyperuricemia in Rats.

Hyperuricemia (HC) is one of the important risk factors for gout, arteriosclerosis, and cardiovascular disease. Animal studies have shown that Lactobacillus plantarum can improve microbiota and immune regulation, as well as inhibit uric acid production. However, it is not clear whether L. plantarum can improve HC and intestinal microbiota. We used potassium oxonate (PO) to induce HC in male SD rats and then treated them with L. plantarum TCI227 in a dose-dependent manner (HC + LD, HC + MD, HC + HD) for 4 weeks. We examined organ weight, conducted biochemical examinations of blood and urine, and analyzed the intestinal microbiota in feces through a 16s rDNA sequence analysis. In this study, TCI227 improved body weight, decreased creatinine and serum uric acid, and increased urine uric acid compared to the HC group. Furthermore, TCI227 increased short-chain fatty acids (SCFAs). In the fecal microbiota (family), TCI227 increased the level of Lactobacillaceae and then decreased the levels of Deferribacteres and Prevotellaceae compared to the HC group. Finally, in the fecal microbiota (genus), TCI227 decreased the level of Prevotella and then increased the levels of Lactobacillus and Ruminococcus compared to the HC group. This study suggested that TCI227 can improve HC and can change the composition of intestinal microbiota in PO-induced male HC SD rats.

Dental pulp stem cells retain mesenchymal phenotype despite differentiation toward retinal neuronal fate in vitro.

Dental pulp stem cells (DPSCs) are an easily accessible, heterogenous source of mesenchymal stem cells (MSCs) that are derived from the neural crest. Evidence suggests that they have neurotrophic qualities in their undifferentiated state and can also be differentiated into neuronal and retinal cell types. There is growing interest in using DPSCs in cell-based therapies to treat glaucoma and blinding retinal diseases. However, careful characterization of these cells is necessary as direct intravitreal and subretinal MSC transplantation is known to lead to deleterious glial reaction and fibrosis. In this study, we provide evidence for the mesenchymal-predominant nature of DPSCs and show that DPSCs maintain their mesenchymal phenotype despite upregulating mature retinal markers under retinal differentiation conditions. CD56, which was previously thought to be a specific marker of neural crest lineage, is robustly co-expressed with mesenchymal markers and may not be adequate for isolating a subpopulation of neural crest cells in DPSCs. Therefore, identification of more specific markers is required to elucidate the heterogeneity of the population and to successfully isolate a putative neural stem cell population before DPSCs can be used for retinal therapy.

Quercetin supplementation attenuates cisplatin induced myelosuppression in mice through regulation of hematopoietic growth factors and hematopoietic inhibitory factors.

The present study investigated the effects of quercetin on cisplatin (CDDP)-induced common side effect, myelosuppression, and the possible mechanisms in Balb/c mice. The mice were randomly treated with CDDP alone or in combination with quercetin for 14 days. Quercetin was given by intraperitoneal injection (10 mg/kg, 3 times a week; IQ) or by a diet containing 0.1% or 1% quercetin (LQ and HQ, respectively). We found that quercetin supplementation especially HQ and IQ, significantly restored the decrease in number of bone marrow cells, total white blood cells, red blood cells and platelets, and the body weight in mice exposed to CDDP (P≤.05). Similar trends were observed in the number of neutrophils, lymphocytes and monocytes in the plasma. HQ and IQ also increased the levels of hematopoietic growth factors (HGFs), especially in granulocyte-macrophage-colony stimulating factor and IL-9 (P<.05), but decreased the levels of hematopoietic inhibitory factors (HIFs) and oxidative stress in the plasma and the bone marrow in CDDP-exposed mice. Furthermore, both quercetin and quercetin-3-O-glucuronide (Q3G) significantly increase cell viability and inhibited apoptosis at 48 or 72 h (P≤.05), accompanied by increasing HGF levels and decreasing HIF levels in the cultured medium in 32D cells exposed to CDDP. IL-9 siRNA transfection suppressed the effects of quercetin and Q3G on cell viability (P≤.05) in32D cells. In conclusion, our results indicate that quercetin attenuates CDDP-induced myelosuppression through the mechanisms associated with regulation of HGFs and HIFs.

Long noncoding RNA Smyca coactivates TGF-ß/Smad and Myc pathways to drive tumor progression.

BACKGROUND: Metastasis and chemoresistance are major culprits of cancer mortality, but factors contributing to these processes are incompletely understood. METHODS: Bioinformatics methods were used to identify the relations of Smyca expression to clinicopathological features of human cancers. RNA-sequencing analysis was used to reveal Smyca-regulated transcriptome. RNA pull-down and RNA immunoprecipitation were used to examine the binding of Smyca to Smad3/4 and c-Myc/Max. Chromatin immunoprecipitation and chromatin isolation by RNA purification were used to determine the binding of transcription factors and Smyca to various gene loci, respectively. Real-time RT-PCR and luciferase assay were used to examine gene expression levels and promoter activities, respectively. Xenograft mouse models were performed to evaluate the effects of Smyca on metastasis and chemoresistance. Nanoparticle-assisted gapmer antisense oligonucleotides delivery was used to target Smyca in vivo. RESULTS: We identify lncRNA Smyca for its association with poor prognosis of many cancer types. Smyca potentiates metabolic reprogramming, migration, invasion, cancer stemness, metastasis and chemoresistance. Mechanistically, Smyca enhances TGF-ß/Smad signaling by acting as a scaffold for promoting Smad3/Smad4 association and further serves as a Smad target to amplify/prolong TGF-ß signaling. Additionally, Smyca potentiates c-Myc-mediated transcription by enhancing the recruitment of c-Myc/Max complex to a set of target promoters and c-Myc binding to TRRAP. Through potentiating TGF-ß and c-Myc pathways, Smyca synergizes the Warburg effect elicited by both pathways but evades the anti-proliferative effect of TGF-ß. Targeting Smyca prevents metastasis and overcomes chemoresistance. CONCLUSIONS: This study uncovers a lncRNA that coordinates tumor-relevant pathways to orchestra a pro-tumor program and establishes the clinical values of Smyca in cancer prognosis and therapy.

Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay.

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. METHODS: The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. RESULTS AND CONCLUSION: We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico. In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant (K d) = 0.468 µM, 1.712 µM, 6.650 µM, 2.86 µM, 3.761 µM and 4.27 µM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50-90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC50 > 100 µM; dioscin and celastrol showed IC50 = 1.5625 µM and 0.9866 µM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. SECTION 1: Natural Products. TAXONOMY CLASSIFICATION BY EVISE: SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study.

Time-course gait pattern analysis in a rat model of foot drop induced by ventral root avulsion injury.

Foot drop is a common clinical gait impairment characterized by the inability to raise the foot or toes during walking due to the weakness of the dorsiflexors of the foot. Lumbar spine disorders are common neurogenic causes of foot drop. The accurate prognosis and treatment protocols of foot drop are not well delineated in the scientific literature due to the heterogeneity of the underlying lumbar spine disorders, different severities, and distinct definitions of the disease. For translational purposes, the use of animal disease models could be the best way to investigate the pathogenesis of foot drop and help develop effective therapeutic strategies for foot drops. However, no relevant and reproducible foot drop animal models with a suitable gait analysis method were developed for the observation of foot drop symptoms. Therefore, the present study aimed to develop a ventral root avulsion (VRA)-induced foot drop rat model and record detailed time-course changes of gait pattern following L5, L6, or L5 + L6 VRA surgery. Our results suggested that L5 + L6 VRA rats exhibited changes in gait patterns, as compared to sham lesion rats, including a significant reduction of walking speed, step length, toe spread, and swing phase time, as well as an increased duration of the stance phase time. The ankle kinematic data exhibited that the ankle joint angle increased during the mid-swing stage, indicating a significant foot drop pattern during locomotion. Time-course observations displayed that these gait impairments occurred as early as the first-day post-lesion and gradually recovered 7-14 days post-injury. We conclude that the proposed foot drop rat model with a video-based gait analysis approach can precisely detect the foot drop pattern induced by VRA in rats, which can provide insight into the compensatory changes and recovery in gait patterns and might be useful for serving as a translational platform bridging human and animal studies for developing novel therapeutic strategies for foot drop.

B cells support the repair of injured tissues by adopting MyD88-dependent regulatory functions and phenotype.

Exogenously applied mature naïve B220+ /CD19+ /IgM+ /IgD+ B cells are strongly protective in the context of tissue injury. However, the mechanisms by which B cells detect tissue injury and aid repair remain elusive. Here, we show in distinct models of skin and brain injury that MyD88-dependent toll-like receptor (TLR) signaling through TLR2/6 and TLR4 is essential for the protective benefit of B cells in vivo, while B cell-specific deletion of MyD88 abrogated this effect. The B cell response to injury was multi-modal with simultaneous production of both regulatory cytokines, such as IL-10, IL-35, and transforming growth factor beta (TGFß), and inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), IL-6, and interferon gamma. Cytometry analysis showed that this response was time and environment-dependent in vivo, with 20%-30% of applied B cells adopting an immune modulatory phenotype with high co-expression of anti- and pro-inflammatory cytokines after 18-48 h at the injury site. B cell treatment reduced the expression of TNFα and increased IL-10 and TGFß in infiltrating immune cells and fibroblasts at the injury site. Proteomic analysis further showed that B cells have a complex time-dependent homeostatic effect on the injured microenvironment, reducing the expression of inflammation-associated proteins, and increasing proteins associated with proliferation, tissue remodeling, and protection from oxidative stress. These findings chart and validate a first mechanistic understanding of the effects of B cells as an immunomodulatory cell therapy in the context of tissue injury.

Healthcare professionals' sense of coherence of parental involvement in neonatal intensive care units: A framework synthesis.

Family-centered care is recognized as the gold standard in pediatric healthcare practice. However, despite the acknowledgment of its benefits and importance, inconsistent and questionable implementation persists in neonatal intensive care units (NICUs) without a consolidated understanding of healthcare professionals' experiences. Therefore, this review aims to explore and consolidate healthcare professionals' perspectives on parental participation in the NICU. A systematic review of qualitative studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seven electronic databases were searched from their respective dates of inception until December 30, 2020. Twenty-eight studies were included in this review. The analysis was conducted via a framework synthesis approach using Antonovsky's Sense of Coherence theory. Three over-arching themes, guided by Antonovsky's Sense of Coherence theory emerged: (1) "Comprehensibility of parental involvement in family-centered care," (2) "Manageability of parental involvement in care and decision-making," and (3) "Meaningfulness of parental involvement in shared decision-making in neonatal care," with nine corresponding subthemes. Healthcare professionals had mixed views of parental involvement, recognizing the benefits attributed to infants and parents, but were greatly hindered by organizational, environmental, and personal obstacles that weakened their sense of coherence in coping with the situation, making them feel unconfident and unprepared to involve parents in care. To cope, more integrated and formalized support was required. Organizational, environmental, and policy changes, as well as psychological support, were strategies identified to enhance healthcare professionals' sense of coherence, and consequently, their ability to cope.