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Restorative dental care is frequently limited to a cycle that begins when patients express their chiefs complaims. As dental caries is recognized as a disease and not merely cavities, it vecomes necessary to diagnose caries before cavities are formed. This diagnosis is much more difficult and can lead to wrong treatment decisions. If periodic maintenance is not provided, the cycle continues with frequent replacement of restorations, often without a valid reason, and closes with disappointed dentist and disappointed patients that decide to change their dentist. This paper reviews the first part of the cycle, related with diagnosis and treatment planning for the active caries patient. It discusses the role of visual inspection, probes, conventional and digitalized radiographs, and electrical conductivity in diagnosis and prognosis of dental caries, and also the influence of correct diagnosis of dental caries in treatment planning.

Se presentan de manera sucinta las características fundamentales de los ionómeros de vidrio que podrían hacer de ellos materiales de interés para el odontopediatra. En particular, se discute su potencial cariostáticos, la adhesividad, la compatibilidad pulpar, y las propiedades físicas, así como sus implicaciones clínicas. Finalmente, se hacen recomendaciones para normalizar la técnica de uso, ya que su sensibilidad es todavía un aspecto crítico.

La atención odontológica restauradora cotidiana ha estado tradicionalmente relacionada con la restitución de la estructura dental pérdida por enfermedad o trauma. Como consecuencia, se han desarrollado de manera espectacular la tecnología y las técnicas para el reemplazo de los tejidos duros dentales. Parte importantísima de este proceso es la investigación e implementación continua de nuevos materiales restauradores, así como la modificación y mejoramineto de los ya existentes, en busca del material restaurador ideal. Los biomateriales restauradores son sometidos a exigencias de variada indole. Se propone agruparlas en tres categorias interrelacionadas: (1) Biológicas, correspondientes a a aceptación del material por el organismo, en razón de la composición del material, o de sus caracteristicas; (2) Fisico-químicas, que hacen referencia a la capacidad del material para resistir sin deterioro significativo las condiciones bucales, y (3) Sociales, relacionadas con la pertinencia, disponibilidad, estética, facilidad de uso, costo y margen de utilidad, entre otras. Solo a través de la contrastación entre las necesidades reales de los pacientes y las características de los materiales disponibles puede establecerse racionalmente la indicación de un material para cada situación específica, considerando siempre que no existe el material ideal, y que el mejor disponible es el tejido dentario.

Author(s): B. Sönnichsen (corresponding author) [1]; L. B. Koski [1, 6]; A. Walsh [1]; P. Marschall [1, 6]; B. Neumann [1, 6]; M. Brehm [1]; A.-M. Alleaume [1, 6]; J. [...]

Abstract Background The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. Results We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. Conclusions Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology.

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Background: The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. Results: We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. Conclusions: Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology. [ABSTRACT FROM AUTHOR]

Introduction: The sleeve gastrectomy (SG) often requires conversion to Roux-en-Y gastric bypass (RYGB) due to gastroesophageal reflux disorder (GERD). Many postbariatric patients seek body-contouring surgery such as abdominoplasty to remove unwanted skin and fat. Although the number of abdominoplasties performed in postbariatric patients is increasing each year, the number of conversion surgeries is increasing in accordance. This study evaluates the impact of abdominoplasties in patients with prior SG on the development of GERD and the need for conversion to RYGB. Methods: A retrospective study was conducted with 630 patients who underwent conversions from SG to RYGB at our institution between January 2014 and December 2023. Outcomes were stratified for comparison between patients with GERD as an indication for conversion and patients with inadequate weight loss as an indication for conversion. Between the two groups we compared the number of patients with post-SG abdominoplasty and the number of hiatal hernias (HH) seen during conversion surgery. A logistic regression analysis was performed to identify factors independently associated with GERD. Results: There was a statistically significant higher number of abdominoplasties in patients who underwent conversion to RYGB for GERD (29 patients, 8.6%) compared to inadequate weight loss (12 patients, 4.1%), P value .034. However, these patients also had statistically significantly more HH (98 patients, 28.9%) compared to patients with inadequate weight loss as an indication for conversion (46 patients, 15.8%), P value <.001. In the logistic regression comparing these two variables, only the presence of HH seen during surgery was found to be a significant predictor of GERD (odds ratio 2.7, confidence interval 1.7-4.1, P < .001). Conclusion: Our data shows that abdominoplasty surgery does not directly influence the development of GERD in post-SG patients. However, the presence of HH in this population significantly impacts the development of GERD, often necessitating conversion to RYGB.

Background: Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB)., Objective: This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU)., Methods: PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee., Results: Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures., Conclusions: This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. All rights reserved.)

The immunopathogenesis of recurrent vulvovaginal candidiasis (RVVC) is poorly understood. Recently, it was reported that patients with RVVC present a decrease in both the fungicidal capacity of neutrophils and the proliferative capability of peripheral blood mononuclear cells in response to Candida albicans infection, suggesting an alteration in the innate and adaptive immune response. The aim of this study was to determine the in-situ expression, in the vaginal mucosa, of genes associated with the immune response, as well as the serum concentrations of dectin-1, mannose-binding lectin (MBL), and vitamin D in patients with RVVC. A study was carried out on 40 patients with a diagnosis of RVVC and 26 healthy women. Vaginal scrapings were obtained, and the expression of genes that encode cytokines and transcription factors specific for Th1, Th2, Th17, Treg, pro-inflammatory profiles, and enzymes related to oxidative/microbicidal mechanisms was evaluated by quantitiative polymerase chain reaction (qPCR). Additionally, serum levels of vitamin D and the soluble receptors dectin-1 and MBL were determined by enzyme-linked immunosorbent assay (ELISA). In patients with RVVC, a decreased expression of T-bet, RORγ-T, IL-1β, and IL-17, and an increase in the expression of FOXP3, IL-4, IL-8, IL-10, and IL-18 were observed when compared to healthy women: moreover, decreased levels of MBL were also observed in these patients. These results confirm that patients with RVVC present in-situ alterations in both the specific and adaptive immune response against Candida spp., a fact that could be associated with the exaggerated vaginal inflammatory response., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Adoptive cellular therapy (ACT) using memory-like (ML) natural killer (NK) cells, generated through overnight ex vivo activation with IL-12, IL-15, and IL-18, has shown promise for treating hematologic malignancies. We recently reported that a multifunctional fusion molecule, HCW9201, comprising IL-12, IL-15, and IL-18 domains could replace individual cytokines for priming human ML NK cell programming ("Prime" step). However, this approach does not include ex vivo expansion, thereby limiting the ability to test different doses and schedules. Here, we report the design and generation of a multifunctional fusion molecule, HCW9206, consisting of human IL-7, IL-15, and IL-21 cytokines. We observed > 300-fold expansion for HCW9201-primed human NK cells cultured for 14 days with HCW9206 and HCW9101, an IgG1 antibody, recognizing the scaffold domain of HCW9206 ("Expand" step). This expansion was dependent on both HCW9206 cytokines and interactions of the IgG1 mAb with CD16 receptors on NK cells. The resulting "Prime and Expand" ML NK cells exhibited elevated metabolic capacity, stable epigenetic IFNG promoter demethylation, enhanced antitumor activity in vitro and in vivo, and superior persistence in NSG mice. Thus, the "Prime and Expand" strategy represents a simple feeder cell-free approach to streamline manufacturing of clinical-grade ML NK cells to support multidose and off-the-shelf ACT., (© 2024. The Author(s).)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19), leading to a global pandemic. The molecular diagnosis of this virus is mostly performed by collecting upper respiratory samples, which has many disadvantages, including patient discomfort and the need for trained healthcare professionals. Although saliva has emerged as a more comfortable sample, the use of additives to preserve viral RNA is expensive and, in some cases, difficult for self-collection., Method: This study evaluated the diagnostic performance by RT-PCR and stability of self-collected saliva using wide-mouth specimen collection cups without stabilization and/or inactivation buffers for SARS-CoV-2 detection, compared to nasopharyngeal samples and saliva collected with additives. Additionally, the study assessed the acceptability of this sample collection method among participants and healthcare personnel., Results: The study included 1281 volunteers with a 24.6% positive infection rate. Saliva demonstrated comparable diagnostic performance to nasopharyngeal samples, with a sensitivity of 87.6% and specificity of 99.6%, for a total percent agreement of 96.4%. The study also showed that viral RNA in saliva remained stable for at least 72 h at different temperatures. Notably, saliva samples without additives exhibited a lower RdRp Ct compared to samples with additives, suggesting that the absence of stabilization and/or inactivation buffers does not significantly affect its performance. The study highlighted the acceptability of saliva among patients and healthcare personnel due to its noninvasive nature and ease of collection., Conclusions: This research supports the implementation of self-collected saliva as a comfortable and user-friendly alternative sample for SARS-CoV-2 diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Recurrent vulvovaginal candidiasis (RVVC) is an important and underestimated fungal infection., Objective: We aimed to determine the fungicidal and proliferative capacities of neutrophils and peripheral blood mononuclear cells (PBMCs), respectively and the clinical and microbiological characteristics of a cohort of Colombian patients diagnosed with RVVC., Methods: A cross-sectional study was conducted. A total of 66 women were included (40 diagnosed with RVVC and 26 healthy women [HW]). Demographic and clinical data were recorded. Vaginal fluid samples were obtained for isolation, identification and antifungal susceptibility testing of Candida species using selective culture media and the Vitek 2.0® system. Blood samples were also obtained to evaluate cell subpopulations; furthermore, neutrophils and PBMCs were isolated to determine their fungicidal and proliferative capacities, respectively., Results: The median age was 29 (IQR: 34-23) for RVVC and 24 (IQR: 30-23) for HW. Only two species of the genus Candida were identified: Candida albicans (92.5%) and Candida lusitaniae (7.5%). Resistance to fluconazole, voriconazole, flucytosine and amphotericin B was observed on six C. albicans isolates and one C. lusitaniae isolate. Only the family history of vulvovaginal candidiasis was associated with RVVC occurrence. The RVVC group exhibited a significantly higher number of neutrophils but with lower fungicidal activity in comparison to HW; likewise, PBMCs from RVVC patients presented a lower proliferation index when stimulated with C. albicans., Conclusion: Contrary to what has been reported worldwide, in Colombian patients with RVVC, C. albicans was the main isolated species without increased antifungal resistance. The diminished fungicidal and proliferative capacities of neutrophils and PBMCs, respectively, could suggest a possible alteration in the innate and adaptive immune responses., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The term monoclonal gammopathy of renal significance has been used to classify the presence of a monoclonal gammopathy or lymphoproliferative disorders that do not meet hematological criteria for myeloma but instead cause kidney damage. Mostly, post-transplant monoclonal gammopathy of renal significance occurs due to recurrent disease. In contrast, the incidence of de novo post-transplant monoclonal gammopathy of renal significance has not been established, as it is considered a rare disease, presenting a unique challenge in terms of diagnosis, management, and potential impact on graft survival. Here, we report a case of de novo monoclonal gammopathy of renal significance diagnosed after kidney transplantation and its complexity due to a concomitant chronic active antibody-mediated rejection., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Standalone lateral lumbar interbody fusion (SA-LLIF) without posterior instrumentation can be an alternative to 360° fusion in selected cases. This study aimed to investigate quantitative changes in psoas and paraspinal muscle morphology that occur on index levels after SA-LLIF., Methods: Patients undergoing single- or multi-level SA-LLIF at L2/3 to L4/5 who had preoperative and postoperative lumbar MRI scans, the latter performed between 3 and 18 months after surgery for any reason, were retrospectively included. Muscle measurements were performed of the psoas and posterior paraspinal muscles (PPM; erector spinae and multifidus) on index levels using manual segmentation and an automated pixel intensity threshold method to differentiate muscle from fat signal. Changes in the total cross-sectional area (TCSA), the functional cross-sectional area (FCSA), and the percentage of fat infiltration (FI) of these muscles were assessed., Results: A total of 67 patients (55.2% female, age 64.3 ± 10.6 years, BMI 26.9 ± 5.0 kg/m 2 ) with 125 operated levels were included. Follow-up MRI scans were performed after an average of 8.7 ± 4.6 months, primarily for low back pain. Psoas muscle parameters did not change significantly, irrespective of the approach side. Among PPM parameters, the mean TCSA at L4/5 (+ 4.8 ± 12.4%; p = 0.013), and mean FI at L3/4 (+ 3.1 ± 6.5%; p = 0.002) and L4/5 (+ 3.0 ± 7.0%; p = 0.002) significantly increased., Conclusion: Our study demonstrated that SA-LLIF did not alter psoas muscle morphology, underlining its minimally invasive nature. However, FI of PPM significantly increased over time despite the lack of direct tissue damage to posterior structures, suggesting a pain-mediated response and/or the result of segmental immobilization., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro-inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single-nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell-cycle, and senescence-associated pathways in naturally aged mice. Long-term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases., (© 2023 HCW Biologics Inc, Washington University School of Medicine and Nova Southeastern University. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: During the past 2.5 years, select bariatric surgeons in the Commonwealth of Massachusetts have been implementing same-day sleeve gastrectomy (SDSG). Key reasons for this change have been to reduce risks associated with hospitalization in the context of the COVID-19 pandemic and to comply with third-party payer preference to reduce costs., Objective: We aimed to evaluate bariatric surgeons' attitudes about outcomes and morbidity between patients who are hospitalized after sleeve gastrectomy and patients who undergo SDSG., Setting: Beth Israel Deaconess Medical Center in Boston, Massachusetts (teaching hospital of Harvard Medical School)., Methods: This prospective cohort study was conducted among bariatric surgeons practicing in the Commonwealth of Massachusetts. An anonymous web-based questionnaire was distributed using the Research Electronic Data Capture software. A total of 58 bariatric surgeons in Massachusetts were identified and successfully contacted based on registration with the Massachusetts Board of Registration in Medicine, membership in the American Society for Metabolic and Bariatric Surgery, and internet search., Results: A total of 33 bariatric surgeons in Massachusetts completed the survey, yielding a response rate of 56.9%. Among the respondents, 75.76% have not performed SDSG, reporting patient safety as the major concern, and 24.24% had performed SDSG in the past., Conclusion: Survey responses showed no significant differences in surgeon perception between SDSG and hospitalization after surgery. Optimal patient selection was an important factor influencing surgeons' decisions with regard to performing SDSG. However, bariatric surgeons in Massachusetts are reluctant to perform SDSG., (Copyright © 2023. Published by Elsevier Inc.)

Mesenchymal stromal cells (MSC) have been widely used not only for tissue regeneration but also for the treatment of various diseases; however, it has been shown that infection of MSCs by different pathogens can attenuate their intrinsic immunomodulatory properties, affecting the proliferation and differentiation of these cells. Currently, the mechanisms by which MSCs respond to pathogen invasion are poorly understood. Therefore, the objective of the present study was to determine if the infection of bone marrow-derived MSCs, with yeasts of the pathogenic fungus Histoplasma capsulatum affects the activation, differentiation and/or proliferation of the MSCs. The results indicate that MSCs have the ability to phagocytose H. capsulatum yeasts but do not exert a notable antifungal effect. On the contrary, the infection of the MSCs with this fungal pathogen not only modulates the expression of inflammatory mediators by a mechanism dependent on TLR2, TLR4 and Dectin-1 but also affects the viability and differentiation capacity of the MSCs. These findings suggest that infection of MSCs by H. capsulatum could not only affect haematopoiesis but also modulate the immune response in the infected host and, furthermore, these MSCs could provide a niche for the fungus, allowing it to persist and evade the immune response of the host., (© 2022 Wiley-VCH GmbH.)

Atherosclerosis is a chronic inflammatory disease caused by deposition of oxidative low-density lipoprotein (LDL) in the arterial intima which triggers the innate immune response through myeloid cells such as macrophages. Regulatory T cells (Tregs) play an important role in controlling the progression or regression of atherosclerosis by resolving macrophage-mediated inflammatory functions. Interleukin-2 (IL-2) signaling is essential for homeostasis of Tregs. Since recombinant IL-2 has an unfavorable pharmacokinetic profile limiting its therapeutic use, we constructed a fusion protein, designated HCW9302, containing two IL-2 domains linked by an extracellular tissue factor domain. We found that HCW9302 exhibited a longer serum half-life with an approximately 1000-fold higher affinity for the IL-2Rα than IL-2. HCW9302 could be administered to mice at a dosing range that expanded and activated Tregs but not CD4 + effector T cells. In an ApoE -/- mouse model, HCW9302 treatment curtailed the progression of atherosclerosis through Treg activation and expansion, M2 macrophage polarization and myeloid-derived suppressor cell induction. HCW9302 treatment also lessened inflammatory responses in the aorta. Thus, HCW9302 is a potential therapeutic agent to expand and activate Tregs for treatment of inflammatory and autoimmune diseases., Competing Interests: All authors are employed by HCW Biologics, Inc., (Copyright © 2023 Zhu, Li, George, Spanoudis, Gilkes, Shrestha, Liu, Kong, You, Echeverri, Li, Wang, Chaturvedi, Muniz, Egan, Rhode and Wong.)

Objective: To establish the prevalence of arterial hypertension in pediatric patients hospitalized in a tertiary hospital center in Medellin, Colombia for 6 years., Methods: A descriptive cross-sectional study was carried out that reviewed retrospective information obtained from the clinical records of patients under 18 years of age hospitalized at the Pablo Tobón Uribe Hospital in Medellín., Results: From a total of 382 pediatric patients hospitalized in the studied period, a prevalence of hypertension of 30.6% was found. Systolic hypertension prevalence was 23.6% and diastolic 20.7%. Age under 5, treatment with vancomycin and critical care admission increased the risk of being hypertensive during hospitalization., Conclusions: In children the frequency of hypertension in hospitalized patients is higher than the prevalence reported in outpatients. The highest risk group and potentially modifiable factors must be recognized and treatment administered in a timely manner. Secondary complications are low, except for left ventricular hypertrophy, which requires long-term follow-up., (Copyright: © 2023 Permanyer.)