Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol. The same expression pattern was evidenced in both mouse models. Parp14-deficiency caused increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss, and immune cell infiltration in DSS-exposed mice. The absence of Parp14 did not affect the mouse colon bacterial microbiota. Also, the colon leukocyte populations of Parp14-deficient mice were normal. In contrast, bulk tissue RNA-Seq demonstrated that the colon transcriptomes of Parp14-deficient mice were dominated by abnormalities in inflammation and infection responses both prior and after the DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation.

May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey.

INTRODUCTION: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. METHODS: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. RESULTS: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). CONCLUSIONS: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

INTRODUCTION: Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. METHODS: Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. RESULTS: A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3 years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3 mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. CONCLUSIONS: In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.

Implementation of Parenting Programs in Real-World Community Settings: A Scoping Review.

Implementing parenting programs in real-world community settings is fundamental to making effective programs widely available and consequently improving the lives of children and their families. Despite the literature acknowledging that the high-quality implementation of parenting programs is particularly challenging in real-world community settings, little is known about how the programs are implemented in these settings. This scoping review followed the methodological framework described by the Joanna Briggs Institute to map evidence on how evidence-based parenting programs have been implemented under real-world conditions. A systematic search of 12 scientific databases, gray literature, and the reference lists of the included studies identified 1918 records, of which 145 were included in the review. Fifty-three parenting programs were identified in studies documenting implementation in real-world community settings worldwide. Most studies included families in psychosocial risk engaged with family-support agencies. The qualitative synthesis identified several implementation outcomes, adaptations, barriers, and facilitators. Most studies reported a maximum of two implementation outcomes, mainly fidelity and acceptability. Providers frequently made adaptations, mainly to bring down barriers and to tailor the program to improve its fit. Findings highlight the need for a more detailed description of the implementation of programs, with greater consistency in terminology, operationalization, and measurement of implementation outcomes across studies. This will promote a more transparent, consistent, and accurate evaluation and reporting of implementation and increase the public health impact of parenting programs. Future studies should also assess the impact of adaptations and the cost-effectiveness and sustainability of programs in real-world community settings.

Identification of the novel HLA-C*07:852 allele by sequencing-based typing.

The new allele HLA-C*07:852 differs from HLA-C* 07:04:01:01 by one nucleotide substitution in codon 314 in exon 5.

TCRαß/CD19 cell-depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis.

ABSTRACT: TCRαß/CD19 cell depletion is a promising graft manipulation technique frequently used in the context of human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of exvivo T-cell depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median, 47.6 months for surviving patients). With a 5-year cumulative incidence of nonrelapse mortality of 5.2% (95% confidence interval [CI], 2.8%-8.8%) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9%-29.2%), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI, 68.6%-80.9%) and 71.6% (95% CI, 64.4%-77.6%), respectively. Cumulative incidence of both grade II-IV acute and chronic graft-versus-host disease were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including type of disease, use of total body irradiation in the conditioning regimen (hazard ratio [HR], 0.5; 95% CI, 0.26-0.98; P = .04), disease status at HSCT (complete remission [CR] ≥3 vs CR 1/2; HR, 2.23; 95% CI, 1.20-4.16; P = .01), and high levels of pre-HSCT minimal residual disease (HR, 2.09; 95% CI, 1.01-4.33; P = .04) were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable on those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.

Ultrasound-guided pulsed radiofrequency for chronic shoulder pain: a prospective study

Abstract Background and objectives: Chronic shoulder pain is a frequent cause of suffering and impaired quality of life. Treatment includes non-pharmacological and pharmacological therapies, and interventional procedures such as suprascapular nerve blocks and radiofrequency. This prospective study aims to evaluate the efficacy of ultrasound-guided pulsed radiofrequency of suprascapular nerve for chronic shoulder pain in a clinical setting. Methods: Therapeutic efficacy was evaluated through pain intensity using numeric pain rating scale at baseline, immediately, 3, and 6 months after, and patient's motor function improvement. The secondary outcome was patient satisfaction. Results: A total of 34 patients were enrolled and all patients presented a reduction in the numeric pain rating scale immediately after treatment. Pain reduction from baseline to 6 months after the procedure was 34.4% and 36.9% static and dynamic, respectively. The median percentage reduction was statistically significant immediately, 3 and 6 months after. There was also an improvement in range of motion, 39.6% in abduction, 24.1% in flexion, and 29.5% in extension. Ninety percent of patients reported patient's global impression of change superior to six. Conclusion: This study concludes that ultrasound-guided pulsed radiofrequency of suprascapular nerve reduces pain intensity for at least 6 months, accompanied by improvement of motor function and higher levels of patients' satisfaction. Therefore, this technique represents a valid analgesic approach to chronic shoulder pain.

An Overview of Chronic Kidney Disease Pathophysiology: The Impact of Gut Dysbiosis and Oral Disease.

Chronic kidney disease (CKD) is a severe condition and a significant public health issue worldwide, carrying the burden of an increased risk of cardiovascular events and mortality. The traditional factors that promote the onset and progression of CKD are cardiometabolic risk factors like hypertension and diabetes, but non-traditional contributors are escalating. Moreover, gut dysbiosis, inflammation, and an impaired immune response are emerging as crucial mechanisms in the disease pathology. The gut microbiome and kidney disease exert a reciprocal influence commonly referred to as "the gut-kidney axis" through the induction of metabolic, immunological, and endocrine alterations. Periodontal diseases are strictly involved in the gut-kidney axis for their impact on the gut microbiota composition and for the metabolic and immunological alterations occurring in and reciprocally affecting both conditions. This review aims to provide an overview of the dynamic biological interconnections between oral health status, gut, and renal pathophysiology, spotlighting the dynamic oral-gut-kidney axis and raising whether periodontal diseases and gut microbiota can be disease modifiers in CKD. By doing so, we try to offer new insights into therapeutic strategies that may enhance the clinical trajectory of CKD patients, ultimately advancing our quest for improved patient outcomes and well-being.

Correction: Implementation of evidence-based parenting programs under real-world conditions: Protocol for a scoping review.

[This corrects the article DOI: 10.1371/journal.pone.0256392.].

Lifestyle interventions to change trajectories of obesity-related cardiovascular risk from childhood onset to manifestation in adulthood: a joint scientific statement of the task force for childhood health of the European Association of Preventive Cardiology and the European Childhood Obesity Group.

There is an immediate need to optimize cardiovascular (CV) risk management and primary prevention of childhood obesity to timely and more effectively combat the health hazard and socioeconomic burden of CV disease from childhood development to adulthood manifestation. Optimizing screening programs and risk management strategies for obesity-related CV risk in childhood has high potential to change disease trajectories into adulthood. Building on a holistic view on the aetiology of childhood obesity, this document reviews current concepts in primary prevention and risk management strategies by lifestyle interventions. As an additional objective, this scientific statement addresses the high potential for reversibility of CV risk in childhood and comments on the use of modern surrogate markers beyond monitoring weight and body composition. This scientific statement also highlights the clinical importance of quantifying CV risk trajectories and discusses the remaining research gaps and challenges to better promote childhood health in a population-based approach. Finally, this document provides an overview on the lessons to be learned from the presented evidence and identifies key barriers to be targeted by researchers, clinicians, and policymakers to put into practice more effective primary prevention strategies for childhood obesity early in life to combat the burden of CV disease later in life.

Non disseminative nano-strategy against in vivo Staphylococcus aureus biofilms.

Staphylococcus aureus is considered a high priority pathogen by the World Health Organization due to its high prevalence and the potential to form biofilms. Currently, the available treatments for S. aureus biofilm-associated infections do not target the extracellular polymeric substances (EPS) matrix. This matrix is a physical barrier to bactericidal agents, contributing to the increase of antimicrobial tolerance. The present work proposes the development of lipid nanoparticles encapsulating caspofungin (CAS) as a matrix-disruptive nanosystem. The nanoparticles were functionalized with D-amino acids to target the matrix. In a multi-target nano-strategy against S. aureus biofilms, CAS-loaded nanoparticles were combined with a moxifloxacin-loaded nanosystem, as an adjuvant to promote the EPS matrix disruption. In vitro and in vivo studies showed biofilm reduction after combining the two nanosystems. Besides, the combinatory therapy showed no signs of bacterial dissemination into vital organs of mice, while dissemination was observed for the treatment with the free compounds. Additionally, the in vivo biodistribution of the two nanosystems revealed their potential to reach and accumulate in the biofilm region, after intraperitoneal administration. Thus, this nano-strategy based on the encapsulation of matrix-disruptive and antibacterial agents is a promising approach to fight S. aureus biofilms.

Prevalence of Cardiovascular Risk Factors and Related Medical and Lifestyle Interventions Among Italian Cardiovascular Specialists: A Proof-of-Concept Study.

INTRODUCTION: Physicians and researchers in the cardiovascular field are constantly engaged in the promotion of guidelines-directed preventive measures, but whether they are themselves adherent to the same recommendations was only sporadically examined. AIM: To assess awareness of self-exposure to cardiovascular risk factors and related management among cardiovascular specialists. METHODS: During the National Conference of the Italian Society of Hypertension (October 2022), a pilot observational study on consecutive volunteer cardiovascular specialists was conducted. Participants underwent standard sitting and standing blood pressure (BP) measurements and answered a questionnaire regarding modifiable/non modifiable cardiovascular risk factors and related treatments. Based on self-declarations and actual measurements, BP was classified as optimal, normal, high-normal BP, and new hypertension in untreated participants, and as treated/untreated pre-existing hypertension. Controlled hypertension was defined as BP < 140/90 mmHg; age-adjusted lower targets were also applied, according to guidelines. RESULTS: In total, 62 participants (30 F, mean age 43.2 ± 14.8 years) were enrolled; 79% reported regular physical activity; 53% of women and 38% of men were on a low-salt diet. After smoke (19.4%), dyslipidemia was the second most common risk factor (17.7%), often occurring with high BP (26.3%) and left untreated (36.7%). Pre-existing hypertension (11.3%) was often uncontrolled (57.1%) and associated with non-adherence to guidelines-directed lifestyle recommendations. About one in 12 participants was unaware of having high measured BP values. CONCLUSIONS: Despite the specific professional exposure, a margin for improvement in self cardiovascular risk factors awareness and management remains in this exploratory sample of cardiovascular specialists. This pilot research anticipates forthcoming, larger studies during national and international conferences.

Association between metabolic syndrome components and gingival bleeding is women-specific: a nested cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of atherosclerotic risk factors that increases cardiovascular risk. MetS has been associated with periodontitis, but the contribution of single MetS components and any possible sexual dimorphism in this relation remain undetermined. METHODS: Using the third National Health and Nutrition Examination Survey (NHANES III), we performed a nested cross-sectional study to test whether individuals aged > 30 years undergoing periodontal evaluation (population) exposed to ≥ 1 MetS component (exposure) were at increased risk of bleeding/non-bleeding periodontal diseases (outcome) compared to nonexposed individuals, propensity score matched for sex, age, race/ethnicity, and income (controls). The association between MetS components combinations and periodontal diseases was explored overall and across subgroups by sex and smoking. Periodontal health status prediction based on MetS components was assessed. RESULTS: In total, 2258 individuals (n. 1129/group) with nested clinical-demographic features were analyzed. Exposure was associated with gingival bleeding (+ 18% risk for every unitary increase in MetS components, and triple risk when all five were combined), but not with stable periodontitis; the association was specific for women, but not for men, irrespective of smoking. The only MetS feature with significant association in men was high BP with periodontitis. CRP levels significantly increased from health to disease only among exposed women. MetS components did not substantially improve the prediction of bleeding/non-bleeding periodontal disease. CONCLUSION: The observed women-specific association of gingival bleeding with single and combined MetS components advances gender and precision periodontology. Further research is needed to validate and expand these findings.

Impact of 2021 ESC Guidelines for Cardiovascular Disease Prevention on Hypertensive Patients Risk: Secondary Analysis of Save Your Heart Study.

INTRODUCTION: Cardiovascular diseases (CVD) are a leading cause of death worldwide, and several modifiable and unmodifiable risk factors contribute to this burden of disability and mortality. Thus, effective cardiovascular prevention relies on appropriate strategies to control risk factors within the frame of unmodifiable traits. METHODS: We conducted a secondary analysis of treated hypertensive adults aged ≥ 50 years enrolled in Save Your Heart. CVD risk and hypertension control rates based on the 2021 updated European Society of Cardiology guidelines were evaluated. Comparisons with previous standards in terms of risk stratification and hypertension control rates were performed. RESULTS: Among the 512 patients evaluated, with the application of the new parameters for fatal and non-fatal cardiovascular risk assessment, the proportion of individuals at high or very high risk rises from 48.7 to 77.1% of cases. A trend towards lower hypertension control rates was observed based on 2021 European guidelines compared with the 2018 edition (likelihood estimate for difference: 1.76%, 95% CI - 4.1 to 7.6%, p = 0.589). CONCLUSIONS: In this secondary analysis on the Save Your Heart study, the application of the new parameters reported in the European Guidelines for Cardiovascular Prevention 2021 showed a hypertensive population with a very high probability of encountering a fatal or non-fatal cardiovascular event due to failure to control risk factors. For this reason, a better management of risk factors must be the main goal for the patient and all the involved stakeholders.

Oral health as a modifiable risk factor for cardiovascular diseases.

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide with a high socioeconomic burden. Increasing evidence supports a convincing connection with increased cardiovascular risk of periodontal diseases (PD), a group of widespread, debilitating, and costly dysbiotic relapsing-remitting inflammatory diseases of the tissues supporting the teeth. Herein, we ensembled the best available evidence on the connection between CVDs and PD to review the recently emerging concept of the latter as a non-traditional risk factor for CVDs. We focused on oral dysbiosis, inflammation-associated molecular and cellular mechanisms, and epigenetic changes as potential causative links between PD and CVDs. The available evidence on the effects of periodontal treatment on cardiovascular risk factors and diseases was also described.

Practical Guidelines for Patients with Hypertension and Periodontitis.

Arterial hypertension (AH) and periodontitis are among the most common non-communicable chronic diseases worldwide. Besides sharing common risk factors, an increasing body of evidence supports an independent association between the two conditions, with low-grade systemic inflammation acting as the plausible biological link with increased cardiovascular risk. In 2021, the Italian Society of Arterial Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) have joined forces and published a joint report on the relationships between AH and periodontitis, reviewing the existing scientific evidence and underlining the need to increase awareness of the strong connection between the two conditions and promote treatment strategies for the control of gums inflammation in patients with AH. The current document extends the previous joint report, providing clinical practical guidelines aimed to support clinicians in the management of patients who suffer from or are at risk of being affected by both conditions. These recommendations are based on careful consideration of the available evidence as well as of the current guidelines on the management of periodontitis and AH and are supported by SIIA and SIdP.

Hypertension and periodontitis: A joint report by the Italian society of hypertension (SIIA) and the Italian society of periodontology and implantology (SIdP).

An accumulating body of evidence supports an independent association between high blood pressure (BP) and periodontitis, possibly mediated by low-grade inflammation. This joint report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) working group on Hypertension and Periodontitis (Hy-Per Group) provides a review of the evidence on this topic encompassing epidemiology, biological plausibility, relevance, magnitude, and treatment management. Consensus recommendations are provided for health professionals on how to manage BP in individuals showing signs of poor oral health. In summary, (1) large epidemiological studies highlight that individuals with periodontal diseases have increased risk for high/uncontrolled BP independent of confounders; (2) mechanistically, low-grade inflammation might have a causal role in the association; (3) BP profile and control might benefit from periodontal treatment in pre-hypertensive and hypertensive individuals; (4) oral health status should be evaluated as a potential risk factor for high/uncontrolled BP, and effective oral care should be included as an adjunct lifestyle measure during hypertension management. Further research is needed to optimize BP management in individuals with poor oral health.