Novel risk loci for COVID-19 hospitalization among admixed American populations.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

In their own words: Perspectives of IPV survivors on obtaining support within the healthcare system.

BACKGROUND: Almost half of all women in the US experience intimate partner violence (IPV) in their lifetime. The US Preventive Services Task Force recommends IPV screening paired with intervention for women of reproductive age. We aim to understand clinical practices and policies that are beneficial, detrimental, or insufficient to support survivors of IPV in a safety-net healthcare system. METHODS: We sampled 45 women who were 18-64 years old, had experienced IPV within the prior year and were patients in the San Francisco Health Network. We conducted in-depth, semi-structured interviews to elicit their perspectives on disclosing IPV and obtaining support within the healthcare system. We analyzed our data using thematic analysis and grounded theory practices informed by ecological systems theory. FINDINGS: We identified four themes regarding factors that impeded or facilitated discussing and addressing IPV across interpersonal and systemic levels relating to relationship-building, respect, autonomy and resources. (1) Interpersonal barriers included insufficient attention to relationship-building, lack of respect or concern for survivor circumstances, and feeling pressured to disclose IPV or to comply with clinicians' recommended interventions. (2) Interpersonal facilitators consisted of patient-centered IPV inquiry, attentive listening, strength-based counseling and transparency regarding confidentiality. (3) Systemic barriers such as visit time limitations, clinician turn-over and feared loss of autonomy from involvement of governmental systems leading to separation from children or harm to partners, negatively affected interpersonal dynamics. (4) Systemic facilitators involved provision of resources through IPV universal education, on-site access to IPV services, and community partnerships. CONCLUSIONS: Women experiencing IPV in our study reported that relationship-building, respect, autonomy, and IPV-related resources were essential components to providing support, promoting safety, and enabling healing in the healthcare setting. Successful trauma-informed transformation of healthcare systems must optimize interpersonal and systemic factors that improve survivor wellbeing while eliminating barriers.

Altered blood microbiome in patients with HCV-related Child-Pugh class B cirrhosis.

BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.

Cobertura para el diagnóstico y tratamiento de la apnea obstructiva del sueño en Latinoamérica: reporte del Foro Latinoamericano de Sociedades Respiratorias / Coverage for the Diagnosis and Treatment of Obstructive Sleep Apnea in Latin America: Report from the Latin American Forum of Respiratory Societies

Introducción: La Apnea Obstructiva del Sueño (AOS) es un problema de salud pública en Latinoamérica; una región que es heterogénea, con recursos diferentes y sistemas de salud diversos. El objetivo fue describir la información recabada por el Foro Latino-americano de Sociedades Respiratorias sobre el acceso y cobertura para los estudios diagnósticos y tratamiento con CPAP de los pacientes con AOS. Material y Métodos: A través de la Asociación Latinoamericana de Tórax (ALAT), se envió una encuesta a todas las sociedades miembros con preguntas sobre el acceso a diagnóstico, tratamiento y cobertura de seguros privados. Resultados: El foro contó con 15 países. Se reportó la existencia de 396 unidades formales de sueño, 82% privadas y 18% públicas; en 12 países el sistema de salud público (SSP) contrata unidades privadas para otorgar servicios. En todos los países se realiza tanto polisomnografía como poligrafía respiratoria para el diagnóstico. En 8 (53%) países, el SSP cubre el tratamiento con CPAP de la AOS (en Argentina, Guatemala y México esta cobertura es parcial); los seguros privados cubren AOS en 7/15 países. Conclusiones: En Latinoamérica, existen pocas unidades formales de sueño y la mayoría son privadas. Cerca de la mitad de los sistemas de salud pública no cubren su tratamiento y, en la mayoría de los casos, los seguros privados no ofrecen cobertura. Esto deja a nuestra población vulnerable a las complicaciones de la AOS, con un concomitante aumento de la morbimortalidad y costos en salud.

Introduction: Obstructive Sleep Apnea (OSA) is a public health problem in Latin America, which is a heterogeneous region, with different resources and diverse health systems. The objective was to describe the information collected by the Latin American Forum of Respiratory Societies on access and coverage for diagnostic studies and CPAP treatment of patients with OSA. Methods: Through the Latin American Thorax Association (ALAT, Spanish acronym), a survey was sent to all member societies with questions about access to diagnosis, treatment, and private insurance coverage. Results: The forum included 15 countries. The existence of 396 sleep medicine units was reported, 82% private and 18% public; in 12/15 countries the public health system (PHS) contracts private units to provide services. In all countries, both polysomnography and respiratory polygraphy are performed to make the diagnosis. In only 8 (53%) countries the PHS covers the treatment of OSA (in Argentina, Guatemala and Mexico this coverage is partial); private insurance coverage is in 7/15 countries.Conclusions: In Latin America there are few formal sleep units and most are private. About half of public health systems do not cover their treatment and, in most cases, private insurance does not offer coverage. This leaves our population vulnerable to the complications of OSA, with a concomitant increase in morbidity, mortality and health costs.

Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era.

BACKGROUND: Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC). METHODS: Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen. RESULTS: The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups. CONCLUSION: LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.

miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Ultrasound-based jawbone surface quality evaluation after alveolar ridge preservation.

BACKGROUND: Bone readiness for implant placement is typically evaluated by bone quality/density on 2-dimensional radiographs and cone beam computed tomography at an arbitrary time between 3 and 6 months after tooth extraction and alveolar ridge preservation (ARP). The aim of this study is to investigate if high-frequency ultrasound (US) can classify bone readiness in humans, using micro-CT as a reference standard to obtain bone mineral density (BMD) and bone volume fraction (BVTV) of healed sockets receiving ARP in humans. METHODS: A total of 27 bone cores were harvested during the implant surgery from 24 patients who received prior extraction with ARP. US images were taken immediately before the implant surgery at a site co-registered with the tissue biopsy collection location, made possible with a specially designed guide, and then classified into 3 tiers using B-mode image criteria (1) favorable, (2) questionable, and (3) unfavorable. Bone mineral density (hydroxyapatite) and BVTV were obtained from micro-CT as the gold standard. RESULTS: Hydroxyapatite and BVTV were evaluated within the projected US slice plane and thresholded to favorable (>2200 mg/cm3; >0.45 mm3/mm3), questionable (1500-2200 mg/cm3; 0.4-0.45 mm3/mm3), and unfavorable (<1500 mg/cm3; <0.4 mm3/mm3). The present US B-mode classification inversely scales with BMD. Regression analysis showed a significant relation between US classification and BMD as well as BVTV. T-test analysis demonstrated a significant correlation between US reader scores and the gold standard. When comparing Tier 1 with the combination of Tier 2 and 3, US achieved a significant group differentiation relative to mean BMD (p = 0.004, true positive 66.7%, false positive 0%, true negative 100%, false negative 33.3%, specificity 100%, sensitivity 66.7%, receiver operating characteristics area under the curve 0.86). Similar results were found between US-derived tiers and BVTV. CONCLUSION: Preliminary data suggest US could classify jawbone surface quality that correlates with BMD/BVTV and serve as the basis for future development of US-based socket healing evaluation after ARP.

Incidence of pleural effusion with dasatinib and the effect of switching therapy to a different TKI in patients with chronic phase CML.

Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.

Complications Associated With Inferior Vena Cava Filter Retrieval: A Systematic Review.

Inferior vena cava (IVC) filters have been used successfully in high-risk patients to prevent thromboembolism. The filters are widely created as retrievable devices, but complication rates progressively increase during IVC filter retrieval. This study aims to analyze IVC filter retrieval cases and associated complications during and following the procedures regarding dwell times, specific filter types, filter positioning, and advanced retrieval techniques. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to select and analyze relevant articles. A literature search for articles was performed on September 23, 2023, through three research databases: PubMed, ProQuest, and ScienceDirect. The keywords used to identify relevant publications were "IVC Filter retrieval AND complications" and "IVC filter removal AND complications". The articles before 2012 were excluded. Relevant articles were selected based on the inclusion and exclusion criteria. In total, 20,435 articles were found: 812 from PubMed, 15,635 from ProQuest, and 3,988 from Science Direct. Among the exclusions were 18,462 articles, which were excluded in the automatic screening process, leaving 1,973 for manual screening. The manual screening of articles was conducted based on title, abstract, article type, duplicates, and case reports, where 1,918 articles were excluded. Ultimately, 55 articles were included in this review. This study demonstrates that IVC filter retrievals have significant complication rates. Many complications have a common theme: prolonged dwell time and lost follow-up appointments. Therefore, importance should be placed on patient education and implementing strict protocols regarding the timelines of IVC filter removals.

Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy.

Background: Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender. Methods: We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4+ ≥500 cells/mm3, and CD4+/CD8+ ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value). Results: PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls. Conclusion: PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.

The use of digital technologies in peri-implant soft tissue augmentation - A narrative review on planning, measurements, monitoring and aesthetics.

OBJECTIVE: To identify the different uses and modalities of digital technologies to diagnose, plan and monitor peri-implant soft tissue conditions and aesthetics. METHODS: A comprehensive narrative review of pertinent literature was conducted, critically appraising key digital technologies that may assist peri-implant soft tissue augmentation and assessment. An electronic search on four databases including studies published prior to 1st July 2023 was performed and supplemented by a manual search. RESULTS: Predominantly, tools such as cone beam computed tomography (CBCT), intraoral scanning (iOS), intraoral ultrasonography and digital spectrophotometry were commonly to assess and monitor peri-implant soft tissues. The main clinical and research applications included: (i) initial assessment of mucosal thickness, supra-crestal tissue height and keratinized mucosa width, (ii) evaluation of peri-implant soft tissue health and inflammation, (iii) monitoring profilometric changes and midfacial mucosal margin stability over time and (iv) aesthetic evaluation through colour assessment. While evidence for some digital tools may be limited, the integration of digital technologies into peri-implant soft tissue management holds great promise. These technologies offer improved precision, comfort and speed in assessment, benefiting both patients and clinicians. CONCLUSION: As digital technologies progress, their full potential in peri-implant soft tissue augmentation and their value will become more evident with ongoing research. Embracing these innovations and their potential benefits is recommended to ensure that during progress in implant dentistry, patient care is not hindered.

A systematic review of oral wound healing indices.

Wound healing monitoring for abnormality identification and intervention is crucial to securing a successful surgical outcome. Indices have been used to summarize the degree of healing. Given the increasing frequency of regenerative procedures which preserve dentition and implant stability, and the higher esthetic demands, an appraisal of the available indices is needed to identify the current knowledge gap. This study aimed to systematically review published oral wound healing indices and scores. MATERIALS AND METHODS: A complete literature electronic search in 5 databases was conducted by two reviewers. A combination of keywords related to oral wound healing was used. RESULTS: A total of 11 articles were included in the evaluation of various procedures (conventional periodontal procedures, guided tissue regeneration, soft tissue reconstruction procedures, and tooth extractions), at different time points (1 day to 12 weeks), with a focus on diverse clinical signs and symptoms. Frequently evaluated parameters included wound dehiscence/epithelialization (91%), tissue color (redness) (73%), suppuration (55%), swelling/edema (55%), and hemostasis (55%). Other less commonly used parameters include esthetics-related and patient-centered outcomes. CONCLUSION: The available indices evaluate a diverse group of subjective clinical signs and symptoms to estimate the underlying biological healing events and assess the degree of clinical success. The majority of the included indices are not validated. Quantitative and objective subclinical parameters including blood perfusion, biomaterial stability, and completeness of epithelialization, are needed for customized wound healing care and better outcome prediction.

Ultrasonography-Derived Elasticity Estimation of Live Porcine Oral Mucosa.

OBJECTIVES: To investigate the biomechanical properties of porcine oral tissues with in vivo ultrasonography and to compare the difference between oral alveolar mucosa and gingival tissue concerning compressional and tensile mechanical strain. MATERIALS AND METHODS: Sinclair minipigs (6 females and 4 males, 6 to 18 months of age) were anesthetized for ultrasonography. In vivo high-frequency tissue harmonic ultrasound (12/24 MHz) cine-loops were obtained while inducing mechanical tissue stress (0 to 1 N). Post-processing strain analysis was performed in a cardiac speckle tracking software (EchoInsight®). Region of interest (ROI) was placed for gingival and alveolar mucosa tissues for longitudinal (compressional) and tensile strain analyses. A calibrated gel pad was employed to determine the absolute force (pressure) for the measured tissue strain response function. The resulting elasticity data was statistically analyzed using custom Matlab scripts. RESULTS: In total, 38 sonography cine-loops around the third premolars were included in the investigation. The longitudinal strain of alveolar mucosa ε AM L was found to be significantly (P < .05) larger than that of gingiva ε G L . Across the measured force range, ε AM L ~ 1.7 × Îµ G L . Significant differences between alveolar mucosa and gingiva tissues were found for all forces. The tensile strain of the alveolar mucosa ε AM T was found to be ~2 × Îµ G T (on the epithelial surface of the gingiva). Both were statistically significantly different for forces exceeding ~0.08 N. At depth, that is, 500 and 1000 µm below the epithelial surface, the gingiva was found to have less ability to stretch contrary to the alveolar mucosa. Gingival tissue at 500 µm depth has significantly less tensile strain than at its surface and more than at 1000 µm depth. In contrast, the tensile strain of alveolar mucosa is largely independent of depth. CONCLUSION: Ultrasonography can reveal significant differences in oral alveolar mucosal and gingival elastic properties, such as compressional and tensile strain. Under minute forces equivalent to 10 to 40 g, these differences can be observed. As dental ultrasound is a chairside, and noninvasive modality, obtaining real-time images might soon find clinical utility as a new diagnostic tool for the objective and quantitative assessment of periodontal and peri-implant soft tissues in clinical and research realms. As ultrasound is a safe modality with no known bioeffects, longitudinal monitoring of areas of concern would be particularly attractive.

Bilateral Subdiaphragmatic Vagal Nerve Stimulation Using a Novel Waveform Decreases Body Weight, Food Consumption, Adiposity, and Activity in Obesity-Prone Rats.

INTRODUCTION: Obesity affects millions of Americans. The vagal nerves convey the degree of stomach fullness to the brain via afferent visceral fibers. Studies have found that vagal nerve stimulation (VNS) promotes reduced food intake, causes weight loss, and reduces cravings and appetite. METHODS: Here, we evaluate the efficacy of a novel stimulus waveform applied bilaterally to the subdiaphragmatic vagal nerve stimulation (sVNS) for almost 13 weeks. A stimulating cuff electrode was implanted in obesity-prone Sprague Dawley rats maintained on a high-fat diet. Body weight, food consumption, and daily movement were tracked over time and compared against three control groups: sham rats on a high-fat diet that were implanted with non-operational cuffs, rats on a high-fat diet that were not implanted, and rats on a standard diet that were not implanted. RESULTS: Results showed that rats on a high-fat diet that received sVNS attained a similar weight to rats on a standard diet due primarily to a reduction in daily caloric intake. Rats on a high-fat diet that received sVNS had significantly less body fat than other high-fat controls. Rats receiving sVNS also began moving a similar amount to rats on the standard diet. CONCLUSION: Results from this study suggest that bilateral subdiaphragmatic vagal nerve stimulation can alter the rate of growth of rats maintained on a high-fat diet through a reduction in daily caloric intake, returning their body weight to that which is similar to rats on a standard diet over approximately 13 weeks.

Review of Intraoral Vasculature and Implications on Incision Designs of Periodontal and Implant Surgeries.

Currently, the incision design for periodontal and implant surgeries is mainly based on the surgeon's personal preference. The primary aim of this study is to review the intricate periodontal microvascular system and to illustrate the potential impact of commonly applied flap designs on the integrity of this system. A complete literature electronic search resulted in 37 relevant articles. The maxillary, facial, and lingual arteries supply the microvasculature system, including the supraperiosteal, intraligamental, and intraosseous arterioles. These arterioles have their own territories yet are extensively interconnected. The impact of common papilla management techniques are discussed, including tunneling; papilla base, incision, and preservation; and flap-releasing incisions. Flap design can impact reperfusion and blood inflow in the early healing phase, which eventually influences wound closure probability, healing speed, surgical predictability, tissue volume change, and postoperative morbidity. Future studies on the three-dimensional distribution of microvasculature and clinical impact of various flap designs on tissue reperfusion can lead to evidence-based incision selection and improved wound-healing outcomes.

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk.

BACKGROUND: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group). METHODS: We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex. RESULTS: 13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found. CONCLUSIONS: Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.

Anatomy-driven complexity classification for soft-tissue tunneling procedures.

BACKGROUND: The tunnel technique (TUN) preserves the integrity of the papilla by creating envelope flaps that allow for the insertion of a connective tissue graft, and/or biomaterials. METHODS: (1) A comprehensive overview of tunneling flap procedures in the treatment of gingival recessions (GRs) for soft tissue coverage is presented and (2) A classification system for soft and hard tissue anatomy of GR sites which may aid the clinician in determining the surgical complexity is being introduced. RESULTS: A novel clinical classification system is proposed to illustrate complexity levels determined by soft and hard tissue anatomy of GR sites such as the mucogingival junction proximity to the gingival margin, bone morphotype, and mucosal margin thickness. CONCLUSIONS: TUN is highly effective in treating single/multiple GRs. Its limitations are related to variability in surgical site anatomy and operator expertise. A classification system based on anatomical soft and hard tissue variations has been proposed to help identify complexity levels encountered during tunneling procedures. KEY POINTS: Site-related factors directly impact the surgical variables related to tissue trauma, flap tension, soft tissue management, muscle pull, and wound stability during the healing of gingival recessions (GRs). The achievement of expedited and favorable wound healing is crucial to obtaining quantitative and qualitative success in the treatment of GR and the long-term stability of root coverage. A classification system based on anatomical soft and hard tissue variations has been proposed to facilitate tunneling procedures while respecting surgical principles.

A Narrative Review on Oral Mucosa Biomechanics and Clinical Implications of Periodontal and Implant-related Regenerative Procedures.

Healing outcomes of periodontal and implant-related regenerative procedures are closely related to wound stability, which is partially determined by biomechanical properties and behaviors of oral mucosal tissues. Studies on soft tissue behaviors under biomechanical forces in oral regeneration models are scarce. The aims of this review article are to (1) contrast the microstructural differences between the attached gingiva (AM) and lining (LM) mucosa, (2) evaluate biomechanical behaviors of the two mucosal types,and (3) relate residual flap tension to the prevalence of wound opening after regenerative procedures. Results: Compositional and structural differences between the AM and LM explain the biomechanical property differences between AM and LM. Wound destabilizers, including tissue recoil stemming from its viscoelastic property, muscle pull, and inflammatory edema created after the flap releasing procedure for primary wound closure interfere with wound stability. Residual flap tension <0.05 N is a prerequisite for sustained wound closure. Tissues under stress can exert negative cellular changes, resulting in necrosis and wound dehiscence. Conclusion: Biomechanical properties and the variations between AM and LM dictate the degree of wound stability. Efforts should be made to reduce the negative impact of the potential destabilizers to optimize wound stability.