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Purpose: Trilateral retinoblastoma (TRB), intracranial neoplasm in heritable retinoblastoma patients, is a very rare fatal disease. Many ocular oncology centers conduct routine screening of retinoblastoma patients by brain imaging. Nevertheless, there is a debate regarding its ability to prolong TRB patients' survival and the number-needed-to-treat. We recommend baseline screening brain imaging in bilateral retinoblastoma patients, followed by imaging according to clinical need. We aim to see if this screening schedule has an impact on patients' survival., Methods: In a retrospective observational study, we reviewed the medical records of patients diagnosed with bilateral retinoblastoma at a tertiary medical center ocular oncology unit between 1.7.1986 and 1.2.2020, who had at least 36 months follow-up or retinoblastoma-related death. We collected data on patients' demographics, clinical features, systemic evaluation, treatment, follow-up, and outcome., Results: The analysis included 109 patients, 60 males and 49 females, diagnosed with bilateral retinoblastoma at a median age of 7.0 months (range 0.43-70.5 months). Germline mutation was found in 43 patients (39.4%) and somatic mutation in 15 patients (13.8%). Genetic status was not recorded in 51 patients (46.8%). Fifty-eight patients (53.0%) underwent baseline brain imaging (MRI in 42 patients and CT scan in 16 patients), in all of whom it was within normal limits. During a median follow-up of 138 months (range 19-787 months), 35 children had follow-up brain imaging (MRI in 25 patients and CT in 10 patients). One patient developed symptomatic TRB during follow-up, and is alive and disease-free (0.9%, Cl:0.02%-5.6%). Looking at survival, six patients (5.5%) developed metastatic disease, and eight patients (7.3%) expired, in all of whom death was retinoblastoma-related., Conclusions: Due to TRB rarity, routine screening by baseline brain MRI may be sufficient, avoiding anesthesia, expenses, distress, and unnecessary interventions, without a significant impact on patients' survival. Nevertheless, due to TRB fatality and treatment morbidity, periodic brain MRI until age 3 is a legitimate option.

Purpose: Interproximal contact loss (ICL) is considered a prevalent complication for a tooth abutting an implant restoration. While numerous potential causes for ICL have been presented, there is no consensus. A review of the current literature with a focus on possible risk factors was performed., Materials and Methods: A PubMed search using keywords "implant OR dental implants OR implant supported prosthesis AND proximal contact loss OR ICL OR loss of interproximal contact OR open contact OR interproximal open contact OR adjacent natural teeth" resulted in 81 citations, 9 of which were relevant to the focus question. Additional references were culled from the reference lists in the identified articles. Systematic reviews, case series, and case reports were reviewed with a focus on causation, association, or correlation., Results: Eight systematic reviews and 14 case series were reviewed. The prevalence of ICL has been reported to be as low as 16% and as high as 66%. ICL was more common on the mesial side of implants and when a tooth abuts a splinted implant restoration. The absence of a uniform definition to accurately describe an interproximal (IP) contact and an open IP contact is demonstrated in the literature. A lack of standardized measurement strategies that relate to a needed consensus definition further exacerbates the broad range of reported results regarding ICL. The lack of controls for almost all the ICL literature makes it difficult to draw conclusions and comparisons to unrestored, natural tooth IP contacts and the prevalence of ICL in this patient population. As a result, the available studies are inadequate to support a causal theory and the potential risk factors associated with ICL., Conclusions: There is a large range of reported prevalence for IP contact loss. ICL is more common when a natural tooth abuts a splinted implant restoration. ICL is more common on the mesial, as opposed to the distal, of an implant retained restoration. Consensus in the definition and measurement strategies for ICL needs to be established to provide standardized terminology and methodology. Potential risk factors such as occlusion, restorative material, and tooth contact area need to be investigated., (© 2024 by the American College of Prosthodontists.)

Introduction: Children with chronic diseases tend to experience a considerably higher burden of oral disease compared to their healthy peers. Low awareness of the impact of systemic diseases on oral health, lack of motivation, and discomfort may render the maintenance of good oral hygiene challenging. We conducted a study of four groups of parents: of children with congenital heart disease (CHD), with diabetes mellitus type 1 (DM), and undergoing anti-cancer treatment (ACT); and a control group of healthy children (C). We aimed to compare between the groups, parental attitudes and knowledge of their children's oral health, and their reports of their children's dental habits., Methods: Parents who arrived with their children for routine check-ups at three main clinics: cardiology, endocrinology, and hematology-oncology were asked to respond to a questionnaire regarding their children's oral and dental health., Results: A total of 287 questionnaires were collected from 76 parents of children with CHD, 100 parents of children with DM, 50 parents of children undergoing ACT, and 61 parents who comprised group C. Compared to the CHD and DM groups, the ACT group demonstrated significantly more awareness of the importance of maintaining oral and dental health following diagnosis of their children's medical condition. Mothers' education was found to correlate with dental health knowledge. Most children in the DM and C groups had previous dental examinations, compared to only half in the CHD and ACT groups. A higher proportion of the children in the C than the other groups brushed teeth twice daily. The groups were similar in their consumption of sugary drinks, and of sweets and snacks. The children's specialist physicians were the main source of information on oral health, especially in the ACT group., Conclusions: Although most of the parents reported awareness to the oral health aspects of their children's disease, only part of them reported that their children visited dentists, and brushed their teeth twice daily. For the parents of children with CHD, DM, and ACT, their children's treating specialists were the primary source of information regarding oral health. This highlights the importance of clear and continuous communication between pediatric specialists and dentists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Halperson, Badarneh, Zion, Kruchenezki, Goldstein, Gavri, Zangen and Fux-Noy.)

Background: F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population., Methods: 191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmax CLN ), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmax CLN was estimated using linear regression models., Results: Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmax CLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmax CLN . However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmax CLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years., Conclusion: SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients., Trial Was Registered: In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022., (© 2024. The Author(s).)

Purpose: Complications can and do occur with implants and their restorations with causes having been proposed for some single implant complications but not for others., Methods: A review of pertinent literature was conducted. A PubMed search of vibration, movement, and dentistry had 175 citations, while stress waves, movement, and dentistry had zero citations as did stress waves, movement. This paper discusses the physics of vibration, elastic and inelastic collision, and stress waves as potentially causative factors related to clinical complications., Results: Multiple potential causes for interproximal contact loss have been presented, but it has not been fully understood. Likewise, theories have been suggested regarding the intrusion of natural teeth when they are connected to an implant as part of a fixed partial denture as well as intrusion when a tooth is located between adjacent implants, but the process of intrusion, and resultant extrusion, is not fully understood. A third complication with single implants and their crowns is abutment screw loosening with several of the clinical characteristics having been discussed but without determining the underlying process(es)., Conclusions: Interproximal contact loss, natural tooth intrusion, and abutment screw loosening are common complications that occur with implant retained restorations. Occlusion is a significant confounding variable. The hypothesis is that vibration, or possibly stress waves, generated from occlusal impact forces on implant crowns and transmitted to adjacent teeth, are the causative factors in these events. Since occlusion appears to play a role in these complications, it is recommended that occlusal contacts provide centralized stability on implant crowns and not be located on any inclined surfaces that transmit lateral forces that could be transmitted to an adjacent tooth and cause interproximal contact loss or intrusion. The intensity, form, and location of proximal contacts between a natural tooth located between adjacent single implant crowns seem to play a role in the intrusion of the natural tooth. Currently, there is a lack of information about the underlying mechanisms related to these occurrences and research is needed to define any confounding variables., (© 2024 by the American College of Prosthodontists.)

Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016-2021) and assessed factors associated with proven/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed 19 proven/probable IFI (11 yeast; eight molds). The proven/probable yeast IFI rate was 6/52 (11.5%) in children who belong to the high risk for IFI category (HR-IFI-AL: high-risk acute lymphocytic leukemia (ALL), acute myeloid leukemia, relapse); and 5/41 (12.2%) in the non-HR-IFI-AL category (standard/intermediate risk ALL). The proven/probable mold IFI rate was 7/52 (13.5%) in HR-IFI-AL children and 1/41 (2.4%) in the non-HR-IFI-AL category. In the multivariable analysis, underlying genetic syndrome, oral mucositis, and older age were significantly associated with proven/probable IFI, while a longer time since AL diagnosis was protective. Two of 13 (15.4%) HR-IFI-AL children died because of IFI. The elevated risks of proven/probable mold IFI and the associated mortality in HR-IFI-AL children, and high risk of invasive candidiasis in the non-HR-IFI-AL group, emphasize the need for the close monitoring of local epidemiology and the adjustment of practices accordingly.

Background: Reverse-transcribed gene copies (retrocopies) have emerged as major sources of evolutionary novelty. MicroRNAs (miRNAs) are small and highly conserved RNA molecules that serve as key post-transcriptional regulators of gene expression. The origin and subsequent evolution of miRNAs have been addressed but not fully elucidated., Results: In this study, we performed a comprehensive investigation of miRNA origination through retroduplicated mRNA sequences (retro-miRs). We identified 17 retro-miRs that emerged from the mRNA retrocopies. Four of these retro-miRs had de novo origins within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and duplicated along with their host mRNAs. We found that retro-miRs were primate-specific, including five retro-miRs conserved among all primates and two human-specific retro-miRs. All retro-miRs were expressed, with predicted and experimentally validated target genes except miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes such as metabolic processes, cell signaling, and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs play a potential oncogenic role in cancer by targeting key cancer genes and are overexpressed in several cancer types, including liver hepatocellular carcinoma and stomach adenocarcinoma., Conclusions: Our findings demonstrated that mRNA retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play important roles in cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Having a child admitted to the PICU is a stressful experience for parents and can have long-term negative mental health consequences. The objective was to determine if formalized expectation setting and bundled consent for invasive procedures upon admission impacts the acute stress burden on parents., Design: Prospective cluster randomized controlled trial., Setting: Single-center, tertiary PICU., Subjects: Parents/guardians of patients, 0-18 years old, admitted to PICU., Interventions: During experimental weeks, all patients admitted to PICU were bundled-consented for common procedures and given a novel unit introductory letter and "Common Procedures Explained" document. During control weeks, all patients were consented for invasive procedures with separate consents for each procedure. Parents then completed a demographic survey and Stress Overload Scale-Short (SOS-S) 48-72 hours after their child's admission. For each participant, the SOS-S generates a Personal Vulnerability (PV) score and an Event Load (EL) score. Parents' perception of the life-threatening nature of their child's condition was also evaluated., Measurements and Main Results: Over 73 weeks, 1,882 patients were screened and 261 consented to the SOS-S. Median PV score was 10.4 in the control group and 9.1 in the experimental group ( p = 0.15). Median EL score was 11.3 for the control group and 10.5 in the experimental group ( p = 0.42). Adjusting for demographic variables and severity of illness, there was no independent association between either PV or EL and bundled consent. However, a parent's perception of threat-to-life was significantly related to the allocated group ( p = 0.036), which resulted in a decreased percentage of parents who rated their child's illness as "Extremely" life-threatening (experimental group, 17% vs control group, 26%)., Conclusions: This study did not demonstrate a decrease in stress when bundled consent was obtained. However, this intervention decreased the parents' perceived severity of illness. Further multicenter studies are needed to evaluate the effects of bundled consent on parents., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Stored water in inner tissues influences the plant water economy, which might be particularly relevant for trees facing increasing dry conditions due to climate change. We studied the water storage in the inner bark and the sapwood of Araucaria araucana (Molina) K. Koch. This species has an extremely thick inner bark and thus it can be used as a model system to assess the impact of internal water storage on plant water balance. Specifically, we analyzed the water circulation pathways in and out of the elastic water storages by using simultaneously frequency domain moisture sensors and dendrometers inserted in the inner bark and in the sapwood, and sap flow determinations during the dry season. The daily patterns of water content and expansion and contraction of the stem tissues were similar to the sap flow pattern. The whole-stem water content and diameter increased in the morning and decreased in the afternoon, contrary to the typical pattern observed in most tree species. An osmotic gradient favoring the water influx from sapwood to inner bark was observed in the morning. There were no lags in the onset of sap flow between different stem heights at the time that recharge of reservoirs occurred. Sap flow at 6 m height was higher than basal sap flow in the afternoon, when the sapwood water content started to decline followed by the water content of the inner bark. Inner bark and sapwood contributed 5-11% to total daily transpiration, allowing the maintenance of high water potentials in the dry season. Our results suggest that the stored water in the stems, the atypical dynamic of recharge and discharge of water from reservoirs and the high tissue capacitance may make an important contribution to the survival of A. araucana during drought periods by maintaining the water balance., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: Real-world data evaluating patients' injection experiences using the latest devices/formulations of the long-acting (LA) somatostatin analogs (SSAs) lanreotide Autogel/Depot (LAN; Somatuline®) and octreotide LA release (OCT; Sandostatin®) are limited., Methods: PRESTO 2 was a 2020/2021 e-survey comparing injection experience of adults with neuroendocrine tumors (NETs) or acromegaly treated with LAN prefilled syringe versus OCT syringe for > 3 months in Canada, Ireland, the UK and the USA (planned sample size, 304)., Primary Endpoint: the proportion of patients with injection-site pain lasting > 2 days after their most recent injection, analyzed using a multivariate logistic regression model. Secondary endpoints included interference with daily life due to injection-site pain and technical injection problems in patients with current SSA use for ≥ 6 months., Results: There were 304 respondents (acromegaly, n = 85; NETs, n = 219; LAN, n = 168; OCT, n = 136; 69.2% female; mean age, 59.6 years). Fewer patients had injection-site pain lasting > 2 days after the most recent injection with LAN (6.0%) than OCT (22.8%); the odds of pain lasting > 2 days were significantly lower for LAN than OCT, adjusted for disease subgroup and occurrence of injection-site reactions (odds ratio [95% confidence interval]: 0.13 [0.06-0.30]; p < 0.0001). Injection-site pain interfered with daily life "a little bit" or "quite a bit" in 37.2% and 3.8% (LAN) versus 52.5% and 7.5% (OCT) of patients, respectively. Among patients with ≥ 6 months' experience with current SSA (92.4% of patients), technical injection problems never occurred in 76.8% (LAN) and 42.9% (OCT) of patients., Conclusions: Compared with OCT, significantly fewer patients using LAN had injection-site pain lasting > 2 days after their most recent injection. Also, fewer LAN-treated patients experienced technical problems during injection. These findings demonstrate the importance of injection modality for overall LA SSA injection experience for patients with acromegaly or NETs., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Introduction: While survival rates among children with cancer are high, a significant proportion of the solid tumors are considered as hard to treat (HTT). Next generation sequencing (NGS) offers the ability to detect molecular changes in tumors. Its implementation may allow usage of targeted therapy for tumors that fail to respond to acceptable oncological treatment. Furthermore, these therapies are characterized by milder side effects than chemotherapy. NGS may also aid in establishing pathological diagnoses and occasionally, identifying cancer-predisposition syndromes. However, the benefit of NGS in the pediatric population is not clear., Aims: Evaluating the benefit of NGS in children with 'HTT' Tumors., Methods: A retrospective study of the usage of NGS in pediatric 'HTT' in the Department of Pediatric Hemato-Oncology at the Hadassah Medical Center. Patients' demographic and clinical characteristics, molecular changes in tumor, their influence on medical decisions and disease course - were all documented., Results: Forty-seven NGS tests from 'HTT' tumors were completed between January 2018 to August 2020. The results of these tests dictated medical decisions in 18 cases (38.3%) while it proved utility in 10 cases (21.3%). Clinical response to targeted therapy, clarification of diagnosis and identification of germline changes were documented in 3 (6.4%), 4 (8.5%) and 3 (6.4%) cases, respectively., Conclusions: The usage of NGS may benefit children with 'HTT' and tumors with difficult diagnoses and in some cases may be life-saving., Discussion: Cost-benefit considerations presumably prevent the assimilation of NGS tests in the standard care of pediatric oncology. It is possible that the current results will strengthen the more accurate usage of theses genomic techniques in children with 'HTT'.

The ever-expanding world of digital technology has produced many changes, including the availability of virtual articulators. The use of such digital technology requires an understanding of the features that have been available with different mechanical articulators. These features include such items as facebow, intercondylar distance, incisal guide table, condylar inclination, reference plane, lateral condylar inclination, immediate mandibular translation, and ability to verify a centric relation record. This paper reviews the adjustable features that have been available with different types of mechanical articulators so that clinicians can determine if these features should be included in the virtual articulators they choose to use. Regardless of whether one is utilizing a mechanical or virtual articulator, the rationale for which type of articulator to select is the same and is predicated on the needs of the patient, the occlusal philosophy of the clinician, and the required accuracy., (© 2022 by the American College of Prosthodontists.)

Clear Cell Sarcoma (CCS), also referred to as malignant melanoma of soft parts, is a rare and aggressive malignant tumor. It comprises 1% of all soft tissue sarcomas and is known to be radio- and chemotherapy resistant. CCS shares morphological and immunohistochemical features with malignant melanoma, including melanin biosynthesis and melanocytic markers. However, it is distinct for the presence of EWSR1-ATF1 translocation which activates MITF transcription factor. We report here of an aggressive case of CCS in a 9-year-old patient, which demonstrates the critical role of molecular analysis in the diagnosis and treatment of uncommon cancer variants in the era of personalized medicine. The EWSR1-ATF1 translocation induces pathological c-Met activation, and so, following unsuccessful CTLA4 and PD-1 blockade immunotherapy, the child received cabozantinib, a small molecule tyrosine kinase inhibitor, with the intent to block c-Met oncogenic effect. In parallel, active immunization, using hapten di-nitrophenyl modified autologous tumor cells was administered with monotherapy PD-1 inhibitor nivolumab. Under this "triplet" therapy, the patient attained an initial partial response and was progression-free for 2 years, in good performance status and resumed schooling. Based on our observation, cabozantinib can be used as an effective and potentially life-prolonging treatment in CCS. We suggest that priming the child's immune system using her autologous tumor and combating T cell exhaustion with PD-1 blockade may have synergized with the targeted therapy. Combining targeted and immunotherapy is a rapidly growing practice in solid tumors and provides a glimpse of hope in situations that previously lacked any treatment option., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sidlik Muskatel, Pillar, Godefroy, Lotem and Goldstein.)

Background and Aims: The ecohydrological significance of leaf wetting due to atmospheric water in arid and semiarid ecosystems is not well understood. In these environments, the inputs of precipitation or dew formation resulting in leaf wetting have positive effects on plant functioning. However, its impact on plant water relations may depend on the degree of leaf surface wettability. In this study we evaluated leaf wettability and other leaf traits and its effects on foliar water uptake and canopy interception in plant species of a Patagonian steppe. We also studied how leaf traits affecting wettability vary seasonally from growing to dry season., Methods: Contact angle of a water droplet with the leaf surface, water adhesion, droplet retention angle, stomatal density, cuticular conductance, canopy interception and maximum foliar water uptake were determined in six dominant shrub species., Key Results: All species increased leaf wettability during the dry season and most species were considered highly wettable. The leaf surface had very high capacity to store and retain water. We found a negative correlation between foliar water uptake and leaf hydrophilia., Conclusions: Despite the diversity of life forms, including cushion shrubs and tall shrubs, as well as phenological variability, all species converged in similar seasonal changes in leaf traits that favour wettability. Intercepted water by crowns and the extremely high capacity of retention of droplets on leaf surfaces can have a significant impact on eco-hydrological process in water limited ecosystems where most of water sources during the growing and the dry season may be small rainfall events or dew, which do not always increase soil water availability., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sclerodermoid graft-versus-host disease (GVHD) is the most severe form of chronic GVHD (cGVHD) and represents a considerable therapeutic challenge. Due to the scarcity of human studies on sclerodermoid cGVHD, the pathogenesis of this entity is not fully understood., Objective: To identify the differential expression of fibrosis-related genes in skin lesions of human lichenoid and sclerodermoid cGVHD and to assess the expression of their corresponding proteins., Methods: PCR array analysis was performed on RNA extracted from three skin biopsies of sclerodermoid cGVHD patients and three normal skin samples, for fibrosis-related gene expression profiles followed by evaluation of their corresponding protein expressions. The expressions of Tissue inhibitor of metalloproteinase 3 (TIMP3), matrix metalloproteinase 1 (MMP1), TIMP1, and TIMP2 were further studied by immunohistochemistry. Demographic, clinical and immunohistochemical parameters of the two cGVHD groups and the control group were compared. The Pearson correlation coefficient was used to assess the correlation between data among the study groups., Results: We identified 44 upregulated and 14 downregulated genes in the skin samples of sclerodermoid cGVHD compared to the control group. TIMP3 was positive in 13/21 biopsies of cGVHD and in one biopsy of the control group. The average staining intensity was significantly higher in the cGVHD group compared to the control group. TIMP3 was expressed mainly in dermal blood vessels. cGVHD specimens with positive TIMP3 staining had a statistically significantly higher total microvascular area than the negative specimens., Conclusion: TIMP3 levels are increased in both subtypes of cGVHD and are associated with increased dermal vascularity., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Purpose: Neuroendocrine tumors (NETs) negatively impact patients' quality of life. Octreotide long-acting release (LAR) and lanreotide depot are somatostatin analogs (SSAs) approved to treat NETs. The study objective was to explore SSA treatment experiences and preferences of patients with NETs., Methods: Qualitative interviews were conducted in US adults (≥ 21 years) with NETs who had ≥ 6 months' treatment with each SSA and transitioned from octreotide LAR to lanreotide depot within the previous year. Participants were asked open-ended questions about their experiences with octreotide LAR and lanreotide depot, treatment preferences, and SSA treatment attributes., Results: Twenty participants (mean age: 58 years; 90% female; 85% white) completed interviews. The most common reasons for treatment transition were doctor recommendation (70%), treatment not working as expected (55%), and injection type preference (45%). Participants reported 34 unique favorable attributes of SSA treatment and 82 unique unfavorable attributes. Symptom control was the most frequently reported favorable attribute (associated with octreotide LAR by 60% of participants and lanreotide depot by 65%). Painful injection (65%) was most frequently cited unfavorable attribute for octreotide LAR and injection experience dependent on administrator (35%) for lanreotide depot. The three SSA treatment attributes rated as most important were side effects, symptom control, and ability to stabilize tumor., Conclusion: Our qualitative data provide valuable insight into the treatment attributes that patients with NETs consider important when making SSA treatment decisions. Factors related to injection administration, side effects, and symptom control are important to patients and should be included in patient-provider communications in clinical contexts., (© 2022. The Author(s).)

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p -value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p -value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p -value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p -value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.

Survival following childhood cancer has increased considerably. In an observational cross-sectional study, we assessed the prevalence of dental developmental anomalies (DDA) among childhood cancer survivors according to types of anticancer treatment. Permanent teeth were examined clinically and radiographically in 121 adolescents with a history of childhood malignancies, to identify DDA, namely hypomineralization or hypoplasia, microdontia, root changes and hypodontia. DDA were observed in 56/121 individuals (46%), in 309/3388 teeth (9%). Hypomineralization or hypoplasia of enamel appeared in 21 (17%) patients. Altered root development appeared in 26 patients and hypodontia affected 13 (10%). Dental anomalies were observed in 36 (43%) individuals who received chemotherapy and not radiation, in 20 (52%) who received radiotherapy, and in 15 (60%) of those who received head and neck radiotherapy. Among patients who received only chemotherapy, young age (6 years or younger) was associated with a higher number of malformed teeth. In conclusion, antineoplastic treatment that combines chemotherapy and radiotherapy appears to increase the risk of DDA. Radiation to the head and neck area was shown to particularly increase the risk of DDA. No specific chemotherapy agent was found to be associated more than the others with DDA., (© 2022. The Author(s).)

Purpose: In a series of publications, Dahl and Krogstad promoted an orthodontic technique for the treatment of severe wear of the anterior teeth that reportedly could induce intrusion of the anteriors and extrusion of the posterior teeth to allow space to restore the worn anterior teeth. The purpose of this Best Evidence Consensus Statement was to evaluate the existing dental literature related to the Dahl Concept., Methods: A PubMed search limited to clinical studies, clinical trials, randomized controlled trials, systematic reviews, meta analyses, and journal articles, using the key words Orthodontics, Dahl appliance, Dahl concept and adult, revealed 11 citations, 9 of which were related. An additional 9 citations were culled from the reference lists in the aforementioned articles., Results: The 20 articles that met the initial search criteria were evaluated and rated. The literature largely focused on the restorative materials that are commonly used to apply the Dahl technique., Conclusions: While there is low-level evidence from a few case series that demonstrated the ability to achieve enough space in the anterior region for the restoration of lost anterior tooth structure, there is no compelling evidence to support any theories as to how that space was achieved. In addition, there is no evidence to support the long-term stability of that position and the restorations. Negative position and restorative outcomes have been reported., (© 2021 by the American College of Prosthodontists.)

Objectives: Agitation and restraint among pediatric psychiatric patients are a frequent, yet little studied, source of morbidity and, rarely, mortality in the emergency department (ED). This study examined agitation and restraint among youth patients in a specialized pediatric psychiatric ED, considering clinical and sociodemographic characteristics of those who required restraint to determine the clinical correlates of agitation and restraint in this population., Methods: This descriptive study was a 6-year retrospective chart review of all patients restrained for acute agitation. Demographics, clinical characteristics, diagnoses, and reasons for restraint were collected. Relationships between sociodemographic and clinical variables to types of restraints used were examined, along with change over the study period in rate of and mean time in restraint., Results: The average restraint rate was 1.94%, which remained fairly consistent throughout study period, although average time in restraint decreased significantly. Restraints were more common in males. Adolescents were overrepresented in the ED population, and after controlling for this, restraint rates were similar in adolescents and younger children. Physical aggression was the most frequent precipitant, although among adolescents verbal aggression was also a precipitant (more so than in younger children). Disruptive behavior disorder diagnoses were most frequently associated with restraint., Conclusions: A lower rate of restraint is reported here than has been seen in programs where youths are treated in medical or adult psychiatric EDs. Hospitals without specialized pediatric psychiatric emergency programs should invest in staff training in deescalation techniques and in access to pediatric psychiatric treatment. The finding that, of youth restrained, a significant proportion were under 12 years old and/or carried diagnoses not typically associated with aggressive behavior, indicates that crisis prevention, management, and treatment should include younger populations and diverse diagnostic groups, rather than focusing narrowly on older patients with psychotic or substance use disorders., Competing Interests: Disclosure: J.H. is on the Clinical Advisory Board of Mindyra. S.A., S.H., K.L., G.G., and R.G. report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Low temperatures and drought are the main environmental factors affecting plant growth and productivity across most of the terrestrial biomes. The objective of this study was to analyze the effects of water deficits before the onset of low temperatures in winter to enhance freezing resistance in olive trees. The study was carried out near the coast of Chubut, Argentina. Plants of five olive cultivars were grown outdoor in pots and exposed to different water deficit treatments. We assessed leaf water relations, ice nucleation temperature (INT), cell damage (LT50), plant growth and leaf nitrogen content during summer and winter in all cultivars and across water deficit treatments. Leaf INT and LT50 decreased significantly from summer to winter within each cultivar and between treatments. We observed a trade-off between resources allocation to freezing resistance and vegetative growth, such that an improvement in resistance to sub-zero temperatures was associated with lower growth in tree height. Water deficit applied during summer increased the amount of osmotically active solutes and decreased the leaf water potentials. This type of legacy effect persists during the winter after the water deficit even when treatment was removed by natural rainfalls., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Long-acting somatostatin analogs (LA SSAs) are approved and recommended for the treatment of patients with advanced neuroendocrine tumors (NETs). Given the long duration of therapy and differences in administration routes, it is important to understand patients' experiences with receiving LA SSA injections., Methods: We conducted a serial survey, informed by qualitative interviews with eight patients treated with LA SSAs and two nurses who administer LA SSA injections, among patients undergoing LA SSA treatment over a 28-day period (administered at baseline and 14 days and 28 days after injection). Eligible patients, recruited by the Carcinoid Cancer Foundation, self-reported having received an LA SSA injection for physician-diagnosed NET within the 5 days before the survey., Results: 202 patients completed the survey at baseline (82 receiving lanreotide and 120 receiving octreotide), 148 at day 14, and 124 at day 28. Patients reported consistently high satisfaction levels with their most recent LA SSA injection (91.1% at baseline, 85.1% at day 14, and 85.5% at day 28); 68.8% reported that their injection experience differed based on the nursing staff administering the injection., Conclusions: Satisfaction with LA SSA injections is high among patients in this population, and specific experiences with LA SSA injections varied based on the nursing staff administering the injection. Evaluations of patients' experiences and satisfaction with treatment are increasingly important as patients take more active roles in decision-making for their treatment pathways., (© 2021. The Author(s).)

Background: COVID-19, the novel coronavirus has caused a global pandemic affecting millions of people around the world. Although children, including children with cancer, have been found to be affected less commonly and less severely than adults, indirect effects of the pandemic on the diagnosis and treatment of children with cancer have been less described., Methods: A survey was performed in the four largest tertiary pediatric hematology-oncology medical centers in Israel. Clinical and laboratory data were collected from the medical files of patients diagnosed or treated with cancer during April-October 2020., Results: Seventeen patients are described, who had a significant delay in diagnosis or treatment of cancer. These represent approximately 10% of all pediatric cancer diagnosed during the study period in these centers. A main cause of delay was fear of exposure to COVID-19 (fears felt by the patient, parent, physician, or decision-makers at the institution; or the implementation of national guidelines). Delays also resulted from co-infection with COVID-19 and the attribution of the oncologic symptoms to the infection. In addition, treatment was delayed of patients already diagnosed with cancer, due to COVID-19 infection detected in the patient, a family member, or a bone marrow donor., Conclusion: Fear from the COVID-19 pandemic may result in delayed diagnosis and treatment of children with cancer, which may carry a risk to dismal prognosis. It is crucial that pediatricians and patients alike remember that other diseases still prevail and must be thought of and treated in a timely fashion., (© 2021. Japan Society of Clinical Oncology.)

Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used to treat patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017 and 2020 using either cyclophosphamide (4 g/m 2 ) plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. Although total CD34 +  yield was higher after chemomobilization compared with G-CSF +/- PXF (median, 13.6 × 10 6 /kg versus 4.4 × 10 6 /kg; P < .01), achievement of ≥2 × 10 6  CD34 + cells (95% versus 93.7%; P = .61) and rates of mobilization failure (5% versus 6.3%; P = .61) were similar. Fewer patients required PXF with chemomobilization (12.3% versus 49.5%; P < .01), and apheresis sessions were fewer (median, 1 [range, 1 to 4] versus 2 [range, 1 to 5]). The rate of complications, including neutropenic fever, emergency department visits, and hospitalizations, was higher after chemomobilization (30% versus 7.4%; P < .01). Previous use of ≤6 cycles of lenalidomide did not impair cell yield in either group. The median cost of mobilization was 17.4% lower in the G-CSF +/- PXF group (P = .01). Between group differences in time to engraftment were not clinically significant. Given similar rates of successful mobilization, similar engraftment time, and less toxicity and lower costs compared with chemomobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

We present a quantum algorithm for simulation of quantum field theory in the light-front formulation and demonstrate how existing quantum devices can be used to study the structure of bound states in relativistic nuclear physics. Specifically, we apply the Variational Quantum Eigensolver algorithm to find the ground state of the light-front Hamiltonian obtained within the Basis Light-Front Quantization (BLFQ) framework. The BLFQ formulation of quantum field theory allows one to readily import techniques developed for digital quantum simulation of quantum chemistry. This provides a method that can be scaled up to simulation of full, relativistic quantum field theories in the quantum advantage regime. As an illustration, we calculate the mass, mass radius, decay constant, electromagnetic form factor, and charge radius of the pion on the IBM Vigo chip. This is the first time that the light-front approach to quantum field theory has been used to enable simulation of a real physical system on a quantum computer.

Purpose: Patients in need of extensive prosthodontic treatment may need restoration of their occlusal vertical dimension (OVD) due to tooth wear, tooth loss, or changes that have occurred to existing prostheses over time. Prosthodontic treatment is based on the clinical application of the available evidence regarding interocclusal distance (IOD), the positional stability of rest vertical dimension (RVD), and the effect of altering the OVD. Hence, the purpose of this consensus document is to examine available data related to IOD, RVD, and alteration of the OVD., Materials and Methods: The search was limited to Clinical trials, Randomized Controlled Trials, Systematic Reviews and Meta-analyses. Key words were healthy patient, mean, range, interocclusal rest distance; healthy patient, mean, range, freeway space; and dentistry, interocclusal gap, and no citations appeared. Dentistry, interocclusal distance, revealed 5 not relevant citations. Dentistry, inter occlusal rest space, and dentistry, interocclusal rest distance, both had the same single not relevant citation. Dentistry, freeway space revealed over 7,000 citations. Dentistry, occlusal vertical dimension, revealed 253 citations, 7 of which were related to the search question but only 1 which was different from the previous search. Mandible, rest vertical dimension, age changes, found 7 citations, none relative to the question. Expanding the search to include journal article found 260 citations with only one relevant to the question. Mandible, rest vertical dimension, alteration, harm revealed no citations; mandible, occlusal vertical dimension, alteration, revealed 15 citations, 1 of which was relevant; mandible, occlusal vertical dimension, changes, revealed 75 citations, none of which were relevant; mandible, occlusal vertical dimension, rehabilitation revealed 10 citations, none of which were relevant. Expanding the search strategy to include Journal article, mandible, occlusal vertical dimension, alteration, received 159 citations, 4 of which were relevant; mandible, occlusal vertical dimension, restoration revealed 208 citations, 1 of which was relevant. Numerous other articles were culled by going through the reference lists of the aforementioned articles., Results: For IOD, 27 articles were found relevant to the search question, which confirmed a mean of 3.0 mm with ranges from 1 to 9 mm. Five articles revealed little evidence as to whether the RVD changes during life. For OVD, 20 articles, including 4 systematic reviews, revealed some evidence that skeletal growth continues from mid adolescence into mid adulthood; strong anecdotal evidence that some unopposed teeth will continue to erupt; no clinical evidence to support the concept that abraded teeth in occlusion in a patient with bruxism will undergo continuous eruption; and some evidence from clinical case reports that restoring OVD in patients with severe abrasion is a successful treatment., Conclusions: There is a range of dimensions for the interocclusal distance (IOD) with many normal dental patients functioning with a higher or lower IOD than the commonly used 3.0 mm average dimension. The resting vertical dimension (RVD) is a 3-dimensional range with little evidence related to changes in the RVD during life. However, aging can cause a decrease in muscle tone which could affect the RVD. The restoration of the OVD can be successfully accomplished if proper diagnosis and treatment planning are performed., (© 2021 by the American College of Prosthodontists.)

Purpose: Numerous studies have focused on the various complications with implant-retained restorations and a common thread in these publications is the potential for occlusal overload. The purpose of this Best Evidence Consensus Statement on implant occlusal schemes was to review the literature to determine the level of scientific evidence upon which the articles are based., Materials and Methods: Limiting the search to Clinical trials, Randomized Controlled Trials, Systematic Reviews, Meta-analyses, the key words: dental implants, occlusion, found no citations. Expanding the search to Journal articles found 1,483 results, 20 of which pertained to the question. Doing a similar search including Journal Articles, the key words: dental implants and occlusal scheme found 47 citations, 17 of which were pertinent to the question., Results: After eliminating duplicates and non-relevant articles, 15 were included in the review. Nineteen additional articles were culled by going through the reference lists in the aforementioned articles., Conclusions: There is a lack of scientific evidence regarding the occlusal scheme utilized with implant restorations that will minimize or eliminate complications. In light of this lack of scientific evidence, the style of occlusion a practitioner utilizes with tooth or mucosal supported prostheses may be used with implant-supported restorations until compelling evidence dictates otherwise., (© 2021 by the American College of Prosthodontists.)

Purpose: The purpose of this Critically Appraised Topic was to investigate the possible clinical relevance of recording the immediate mandibular lateral translation., Materials and Methods: A literature search limited to Clinical trials, Randomized Controlled Trials, Systematic Reviews, Meta Analyses, and using the PICO headings revealed no citations. Using the key words dental, occlusion, immediate side shift, also received no citations. Expanding the search criteria to include Journal Articles revealed 17 citations. Using dental occlusion, Bennett movement, revealed 21 citations., Results: The cited articles were reviewed for relevance and duplicates were eliminated. The resulting 10 English language in vivo studies pertinent to the question were included. Other articles were culled from the author's library and the reference list of the aforementioned articles. There is no evidence on the prevalence of IMLT in patients in need of occlusal rehabilitation. There is agreement that the recording of the IMLT is reference point and recording instrument dependent. There is agreement that IMLT is observable on some patients and is minimal in magnitude. There is no evidence of any adverse clinical events as a result of not including IMLT in a restorative occlusal scheme., Conclusions: It is justifiable to question the necessity of attempting both to record immediate mandibular lateral translation on the average patient and reproduce it on an articulator., (© 2021 by the American College of Prosthodontists.)

Purpose: The purpose of this Best Evidence Consensus Statement is to report on the prevalence, potential causes or association, treatment and cure of bruxism., Materials and Methods: A literature search limited to Clinical Trials, Randomized Controlled Trials, Systematic Reviews and Meta Analyses, with the key words bruxism, and prevalence identified 22 references, bruxism and causation 21, bruxism, and treatment 117, and bruxism and cure none., Results: Prevalence received 5 references which were relevant to the question researched. Causation received 11 relevant references, treatment 34 relevant references and cure none. Eighteen additional references were culled from the reference lists in the aforementioned articles., Conclusions: Due to variations in demographics and the dependence on anamnestic data, the true prevalence of bruxism in any specific population is unknown. There is moderate evidence that psychosocial factors such as stress, mood, distress, nervousness, and feeling blue are associated with sleep bruxism (SB) as well as caffeine, alcohol, and smoking. There is no consensus on what symptoms of SB or awake bruxism (AB) should be treated. There is some evidence that occlusal devices and bio feedback therapies can be utilized in SB treatment. There is conflicting evidence in the use of Botulinum toxin A and no compelling evidence for the use of drug therapy to treat SB. There is not an established cure for bruxism. The clinician is best served in using caution in the dental rehabilitation of patients with severe occlusal wear., (© 2020 by the American College of Prosthodontists.)

Purpose: This Best Evidence Consensus Statement evaluated the existing Angle's classification clinical literature to determine if the Angle's classification as historically determined in maximum intercuspal position (MIP) with hand held casts is coincident with the centric occlusion (CO) determined Angle's classification. In addition, it explored the value of using Angle's classification for edentulous patients MATERIALS AND METHODS: The search strategy was related to the focus questions and limited to Meta-analyses, Systematic Reviews (SR), Randomized Controlled Trials (RCT) and Clinical Trials. Searches were completed using the term Angle's classification and Boolean Modifiers (AND) with the key terms: dental occlusion, dental occlusion centric, centric occlusion, centric relation, maximal intercuspation, MIP, intercuspal position, and edentulous patient, retrognathia, determination, and prognathia. Additional related articles were culled from the reference lists in the articles found in the PubMed searches., Results: The search identified 494 articles related to the selected terminology. Titles were reviewed and selected if related to the focus questions for further review. Seven papers could be identified that addressed the specifics of the questions., Conclusions: There is evidence that the Angle's classification for many patients will change when recorded in CO compared to the historical MIP determination/definition. A different Angle's classification recorded in CO is potentially a significant diagnostic finding for patients needing complete mouth rehabilitation. The current definitions of Angle's Classification are not useful in the management of edentulous patients., (© 2020 by the American College of Prosthodontists.)

Purpose: The objective of this Critically Appraised Topic was to determine the level of evidence relative to the usefulness of the Frankfort mandibular plane angle in prosthodontic treatment., Materials and Methods: The Patient Intervention Comparison Outcome (PICO) mesh heading received zero PubMed references, as did Frankfort Mandibular Plane Angle (FMA) as a determinant for dental occlusion and Frankfort Mandibular Plane Angle as a determinant of the occlusal scheme. Frankfort Mandibular Plane Angle alone received 168 PubMed citations that highlighted 2 DiPietro articles and a third from the orthodontics literature which was a Randomized Controlled Trial not relevant to the PICO. Four others, three prosthodontic and one orthodontic publication, were related to the PICO. A Google search revealed one additional article, which was a narrative review., Results: Nine articles were related to the search, 2 of which were clinical trials that revealed no evidence to support the use of FMA as a diagnostic test., Conclusion: Based on the limited data presented above, there is a lack of evidence to support the use of FMA as a diagnostic procedure to predict outcomes, or dictate prosthodontic treatment., (© 2021 by the American College of Prosthodontists.)

Purpose: The occlusal scheme required for an edentulous patient is controversial. The purpose of this Best Evidence Consensus Statement was to evaluate the existing complete denture literature related to occlusal schemes., Materials and Methods: A literature search was limited to Meta-analyses, Systematic Reviews (SR), Randomized Controlled Studies (RCT) and Clinical Trials. Key Words were: Complete dentures, occlusion, harm; Complete dentures, occlusion alveolar bone loss; Complete dentures, occlusion, stability; Complete dentures, occlusion. Additional related articles were culled from the authors' library and reference lists in the articles found in the PubMed searches., Results: Of the 165 articles that met the initial search criteria, 34 related to the focus questions and were evaluated and rated., Conclusions: There is strong support that the average denture patient, with good residual ridges and no neuromuscular problems, will function adequately with a properly fabricated complete denture regardless of the occlusal scheme. There is neither strong support for or against bilateral balanced occlusal schemes as it relates to patient satisfaction, preference or chewing ability. There is some support for increased alveolar bone loss with complete dentures that have a non-balanced occlusion. There is a need for bilateral balanced occlusal schemes for patients presenting with loss of stability and retention as a result of their presenting conditions (PDI III and IV)., (© 2020 by the American College of Prosthodontists.)

Fluid overload is a common complication of critical illness, associated with increased morbidity and mortality. Pulmonary fluid status is difficult to evaluate clinically and many clinicians utilize chest X-ray (CXR) to identify fluid overload. Adult data have shown lung ultrasound (LUS) to be a more sensitive modality. Our objective was to determine the performance of LUS for detecting fluid overload, with comparison to CXR, in critically ill children. We conducted a systematic review using multiple electronic databases and included studies from inception to November 15, 2020. The sensitivity and specificity of each test were evaluated. Out of 1,209 studies screened, 4 met eligibility criteria. Overall, CXR is reported to have low sensitivity (44-58%) and moderate specificity (52-94%) to detect fluid overload, while LUS is reported to have high sensitivity (90-100%) and specificity (94-100%). Overall, the quality of evidence was moderate, and the gold standard was different in each study. Our systematic review suggests LUS is more sensitive and specific than CXR to identify pulmonary fluid overload in critically ill children. Considering the clinical burden of fluid overload and the relative ease of obtaining LUS, further evaluation of LUS to diagnose volume overload is warranted., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Statement of Problem: There is little evidence on how the multiple layers of zirconia (ZrO 2 ) or glazed material will affect the shear bond strength (SBS) of different resin cements., Purpose: The purpose of this in vitro study was to compare the SBS of 2 resin cements with the different layers of a monolithic polychromatic ZrO 2  ceramic, both glazed and nonglazed, and a lithium disilicate (LDS) ceramic., Material and Methods: One hundred and sixty-eight composite resin cylinders and 48 monolithic polychromic ZrO 2  plates were prepared. Twenty-four were milled and sintered, and 24 were milled and sintered and had a glaze cycle applied with no liquid glaze. These plates and 12 LDS plates were mounted in autopolymerized acrylic resin. Bonding surfaces were polished, airborne-particle abraded, and cleaned ultrasonically. The different layers (cubic, hybrid, and tetragonal) of the ZrO 2  plates were identified and marked. The plates were assigned to 2 cement groups: a self-adhesive, autopolymerized resin cement, and a dual-polymerizing, adhesive resin cement (DPRC). Bonding surfaces were cleaned and treated according to the cement manufacturer's instructions. Three composite resin cylinders were luted to the ZrO 2 plates at the appropriate layer, and 2 cylinders were luted to each LDS plate. The specimens were stored in a moist environment for 24 hours at 37 °C. The SBS test was performed with a universal testing machine. Visual inspections of the debonded surfaces were compared under magnification. The data were analyzed with a 2-way ANOVA and a subsequent Student t test (α=.05)., Results: The 2-way ANOVA found no difference among luting agent and LDS and ZrO 2 . The SBSs of the nonglazed tetragonal and cubic layer to the ZrO 2 were higher than to the surface exposed to a glazing cycle (P=.001). The bonded surfaces were examined tactilely and under ×3.5 magnification, followed by light and scanning electron microscopy and recorded as either adhesive, cohesive, or mixed. Almost all failures in the glazed ZrO 2 were mixed and cohesive. However, more adhesive failures were observed in the DPRC group of nonglazed ZrO 2 ., Conclusions: No differences were found between the 2 luting agents for the LDS. For the ZrO 2  cubic and tetragonal layers, the DPRC had higher bond strengths to the nonglazed surfaces., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer.

Type I and III leukocyte adhesion deficiencies (LADs) are primary immunodeficiency disorders resulting in early death due to infections and additional bleeding tendency in LAD-III. The curative treatment of LAD-I and LAD-III is allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective multicenter study, data were collected using the European Society for Blood and Marrow Transplantation registry; we analyzed data from 84 LAD patients from 33 centers, all receiving an allo-HSCT from 2007 to 2017. The 3-year overall survival estimate (95% confidence interval [CI]) was 83% (74-92) for the entire cohort: 84% (75-94) and 75% (50-100) for LAD-I and LAD-III, respectively. We observed cumulative incidences (95% CI) of graft failure (GF) at 3 years of 17% (9%-26%) and grade II to IV acute graft-versus-host disease (aGVHD) at 100 days of 24% (15%-34%). The estimate (95% CI) at 3 years for GF- and GVHD-II to IV-free survival as event-free survival (EFS) was 56% (46-69) for the entire cohort; 58% (46-72) and 56% (23-88) for LAD-I and LAD-III, respectively. Grade II to IV acute GVHD was a relevant risk factor for death (hazard ratio 3.6; 95% CI 1.4-9.1; P = .006). Patients' age at transplant ≥13 months, transplantation from a nonsibling donor, and any serological cytomegalovirus mismatch in donor-recipient pairs were significantly associated with severe acute GVHD and inferior EFS. The choice of busulfan- or treosulfan-based conditioning, type of GVHD prophylaxis, and serotherapy did not impact overall survival, EFS, or aGVHD. An intrinsic inflammatory component of LAD may contribute to inflammatory complications during allo-HSCT, thus providing the rationale for considering anti-inflammatory therapy pretreatment., (© 2021 by The American Society of Hematology.)

Purpose: The purpose of this Best Evidence Consensus Statement was to evaluate the existing literature on the stomatognathic system's ability to adapt to occlusal changes., Materials and Methods: The search term stomatognathic system was not useful as it resulted in over 400,000 results nor was the search term temporomandibular joint adaptation with 738 results due to the large number of references not related to the topic. The terms stomatognathic system adaptation to occlusal changes (186 results), teeth flexion (139 results), muscle adaptation to dental occlusion (278 results), and occlusal changes and neuroplasticity (11 results) provided the best selection of articles related to the topic. Limiting the above searches to systematic reviews and randomized controlled clinical trials resulted in multiple publications that were related to the question.9-13 Other literature reviews, data-based publications, and expert opinion resources have been included due to their relationship to the question., Results: From the extensive list of search results, 242 articles were determined to be potentially related to the focus question and were evaluated with 56 being included in this paper. It was determined that the stomatognathic system adapts to occlusal changes through the temporomandibular joint, muscles, teeth and bone. The dynamically modified periosteum on the articulator surfaces of the condyle and fossa has a unique load-bearing morphology with 3 subarticular layers of fibrocartilage that absorb and dissipate both peak (impact) and sustained loads. Adaptability of the TMJs and muscles can be documented through studies where artificially produced occlusal interferences were placed in patients and those study participants with normal temporomandibular joints (TMJs) adapted fairly well whereas those with a previous history of temporomandibular disorders (TMD) did not adapt as well., Conclusions: Available evidence indicates patients generally adapt to the occlusal change inherent in orthodontic treatment, mandibular advancement surgery, and the use of mandibular advancement devices. The head and neck muscles also adapt to occlusal changes in patients without a history of TMD. The dentition adapts to changes through the bone and periodontal ligaments as well as the ability of teeth to undergo slight flexion under masticatory loading. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Statement of Problem: Recent studies have shown that torque-limiting devices (TLDs) do not meet their torque targets and are affected by factors such as the use of the TLDs and the sterilization processes used., Purpose: The purpose of this in vitro study was to investigate the accuracy of TLDs currently in use in the Advance Education Program in Prosthodontics at the New York University College of Dentistry., Material and Methods: Five new and 46 in-use TLDs (Nobel BioCare) from the implant kits of the graduate students were evaluated. One investigator was trained and calibrated before testing and after every 10 evaluations. A 3-jaw chuck was mounted on the center of a cap testing device by using the provided mounting screws. A LOCATOR torque driver was clamped into the chuck, and a torque wrench driver was attached to it. The device was placed on a flat table with direct overhead lighting that allowed the investigator to have a consistent view of the notches on the TLDs. A piece of cardboard was attached to the device to ensure that the investigator could not see the readouts. The blinded researcher inserted the wrench and applied the appropriate torque force at the designated notches while another researcher recorded the results. Two readings were made for each TLD at 15, 35, and 45 Ncm. A 2-way ANOVA and an intraclass correlation coefficient to test for intraclinician reliability were performed by using a statistical software program (α=.05)., Results: Two TLDs were damaged and not tested. The 2-way ANOVA demonstrated no significant difference (P>.05) between graduate students in year 1, 2, and 3 or between the autoclaved and new TLDs. The intraclass correlation coefficient was 0.861 for 15 Ncm, 0.589 for 35 Ncm, and 0.764 for 45 Ncm., Conclusions: In this in vitro study, new and used TLDs all met the recommended torque values. No significant differences were found among groups, suggesting that autoclaving and use did not affect the accuracy of the TLDs tested., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Statement of Problem: Although numerous studies have been performed on the accuracy of intraoral scanners, determining the clinical significance of the results is problematic., Purpose: The purpose of this in vitro study was to evaluate the trueness and precision of 4 intraoral optical scanners (IOSs) on a 6-implant model and provide a method to help determine clinical significance., Material and Methods: A polymer mandibular edentulous model with 6 hexagonal scan bodies (Ritter) was fabricated, and a control scan was made by using an industrial laser line probe (FARO Edge HD Arm). Four IOSs (True Definition, TRIOS, CEREC Omnicam, Emerald Scanner) were used to scan the same model 5 times: the 20 standard tessellation language (STL) files were individually imported to a 3D inspection software program (Geomagic Control X) and superimposed over the computer-aided design (CAD) control scan. The tolerance was set at a limit of ±0.01 mm., Results: None of the tested scanners were true even 10% of the time at the ±0.01-mm tolerance, and the Emerald scanner was true less than 5% of the time. Within scanners, results were precise, showing variations of no more than 2% over repeated scans. When a ±0.05-mm tolerance was selected, the percentage within tolerance increased dramatically. This made the performance of the scanners to appear better but obscured valuable information. The 3D color map was the best method for understanding the data. The color maps showed how much was within tolerance and, equally important, the amount and direction of out of tolerance, providing an easily understandable qualitative and quantitative image., Conclusions: No statistical or clinical differences were found among the scanners tested. The 3D map was the best method for observing the data., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The elemental composition of freshwater and saltwater samples around the South Pacific island of Upolu, Samoa has been investigated together with other indicators of water quality. Up to 69 elements from Li (3) to U (92) are measured in each sample, analyzed by Mattauch-Herzog-inductively coupled plasma-mass spectrometry (MH-ICP-MS). One hundred and seventy-six samples were collected from surface freshwater sources (24 rivers, two volcanic lakes, one dam) and from seawater sources from the surface to 30 m depth (45 inner reef, reef, and outer reef locations) around Upolu Island, including river mouths and estuaries. Principal component and hierarchical clustering correlation analyses were performed on quantile normalized log transformed elemental composition data to identify groups of samples with similar characteristics and to improve the visualization of the full spectrum of elements. Human activities, such as the use of herbicides and pesticides, may relate to observed elevated concentrations of some elements contained in chemicals known to have deleterious obesogenic effects on humans that may also cause coral reef decline. Furthermore, the salinity of some saltwater samples tested were very high, possibly due to climate variability, which may additionally harm the health and biodiversity of coral reefs.

Objective: Rapid, high-volume screening programs are needed as part of cervical cancer prevention in China., Methods: In a 5-day screening project in Inner Mongolia, 3345 women volunteered following a community awareness campaign, and self-swabbed to permit rapid HPV testing. Two AmpFire™ HPV detection systems (Atila Biosystems) were sufficient to provide pooled 15-HPV type data within an hour. HPV+ patients had same-day digital colposcopy (DC) performed by 1 of 6 physicians, using the EVA™ system (MobileODT). Digital images were obtained and, after biopsy of suspected lesions for later confirmatory diagnosis, women were treated immediately based on colposcopic impression. Suspected low- grade lesions were offered treatment with thermal ablation (Wisap), and suspected high-grade lesions were treated with LLETZ., Results: Of 3345 women screened, 624 (18.7%) were HPV+. Of these, 88.5% HPV+ women underwent same-day colposcopy and 78 were treated. Later consensus histology results obtained on 197 women indicated 20 CIN2+, of whom 15 were detected and treated/referred at screening (10 by thermal ablation, 4 by LLETZ, 1 by referral)., Conclusions: Global control of cervical cancer will require both vaccination and screening of a huge number of women. This study illustrates a cervical screening strategy that can be used to screen-and-treat large numbers of women. HPV self-sampling facilitates high-volume screening. Specimens can be tested rapidly, promoting minimal loss-to-follow-up. Specifically, the AmpFire™ system used in this study is highly portable, simple, rapid (92 specimens per 65 min per unit), and economical. Visual triage can be performed on HPV+ women with a portable digital colposcope that provides magnification, lighting, and a recorded image. Diagnosis and appropriate treatment remain the most subjective elements. The digital image is under study for deep-learning based automated evaluation that could assist the management decision, either by itself or combined with HPV typing., Competing Interests: Competing interestsAndrew Goldstein: President of the Gynecologic Cancers Research Foundation: a non-profit 501(c)3 corporation. Received research funding from the Gynecologic Cancers Research Foundation. Yang Lei: none to report. Lena Goldstein: none to report. Amelia Goldstein: none to report. Qiao Xu Bai: none to report. Juan Felix: none to report. Roberta Lipson: Director, United Foundation for China’s Health, a non-profit 501(c)3 corporation. Shareholder in MobileODT. Maria Demarco, Mark Schiffman, Didem Egemen, Kanan Desai: NCI has received cervical screening supplies and results at no cost from several companies (Roche, BD, Qiagen, MobileODT) for independent evaluations of test performance. Sarah Bedell: none to report. Janet Gersten: none to report. Gail Goldstein: Is a board member of the Gynecologic Cancers Research Foundation: a non-profit 501(c)3 corporation. Karen O’Keefe: none to report. Casey O’Keefe: none to report. Tierney O’Keefe: none to report. Cathy Sebag: Was an employee of MobileODT during the data collection. Lior Lobel: Was an employee of MobileODT during the data collection. Anna Zhao: employee, United Foundation for China’s Health, a non-profit 501(c)3 corporation. Yan Ling Lu: none to report., (© The Author(s) 2020.)

Objective: Rural Yunnan Province is one of the most ethnically, culturally, and religiously diverse regions in China. The majority of its women have never been screened for cervical cancer. It is not known whether women would feel comfortable and ultimately even prefer using a human papillomavirus (HPV) self-swabbing method., Methods: In a 6-day period, 3,600 women were taught the role of HPV in cervical cancer. They were then given self-swabbing instructions. After obtaining their specimens, 600 women were interviewed about their experience with HPV self-testing. The women were of the Yi, Hui, Dai, and Han ethnicities., Results: The overwhelming majority of the women surveyed understood the self-sampling instructions (588/600, 98%) and felt comfortable carrying out the self-sampling procedure (584/600, 97%). Significantly more women (389/600, 64.8%) preferred self-sampling to having the provider (211/600, 35.2%) obtain the sample (χ = 105.61, p < .05). Women who preferred self-sampling did so primarily because they felt capable of obtaining the specimens (n = 80) or that it was a more convenient way to be tested (n = 79). The medical expertise of the provider (n = 74) and concerns over the accuracy of the test (n = 88) shifted some women's preference toward a provider-obtained sample., Conclusions: There are 400+ million Chinese women who have never had a cervical cancer screening. Self-testing has the potential to significantly increase the number of women tested. Despite the diversity of the women screened, the majority felt comfortable self-sampling and preferred self-swabbing to provider testing.

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

Frost and drought are key stress factors limiting the growth and distribution of tree species. Resistance to stress involves energy costs that may result in trade-offs between different functional traits. Structures or mechanisms that can help to withstand stress imply differences in the carbon economy of the species. Although adaptive responses to frost and drought resistance are usually of a similar nature, they are rarely assessed simultaneously. We investigated these resistance mechanisms in 10 canopy tree species coexisting in the semi-deciduous subtropical forests of northern Argentina. We measured leaf lifespan, anatomical, photosynthetic and water relations traits and performed a thermal analysis in leaves to determined ice nucleation and tissue damage temperatures. Our results showed that evergreen and deciduous species have different adaptive responses to cope with freezing temperatures and water deficits. Evergreen species exhibited cold tolerance, while deciduous species were more resistant to hydraulic dysfunction and showed greater water transport efficiency. Further research is needed to elucidate resistance strategies to stress factors at the whole tree- and stand level, and possible links with hydraulic safety and efficiency among different phenological groups. This will allow us to predict the responses of subtropical forest species to changes in environmental conditions under climate change scenarios.

Foliar water uptake (FWU) has been reported for different species across several ecosystems types. However, little attention has been given to arid ecosystems, where FWU during dew formation or small rain events could ameliorate water deficits. FWU and their effects on leaf water potential (Ψ Leaf ) were evaluated in grasses and shrubs exploring different soil water sources in a Patagonian steppe. Also, seasonal variability in FWU and the role of cell wall elasticity in determining the effects on Ψ Leaf were assessed. Eleven small rain events (< 8 mm) and 45 days with dew formation were recorded during the study period. All species exhibited FWU after experimental wetting. There was a large variability in FWU across species, from 0.04 mmol m -2 s -1 in species with deep roots to 0.75 mmol m -2  s -1 in species with shallow roots. Species-specific mean FWU rates were positively correlated with mean transpiration rates. The increase in Ψ Leaf after leaf wetting varied between 0.65 MPa and 1.67 MPa across species and seasons. The effects of FWU on Ψ Leaf were inversely correlated with cell wall elasticity. FWU integrated over both seasons varied between 28 mol m -2 in species with deep roots to 361 mol m -2 in species with shallow roots. Taking into account the percentage of coverage of each species, accumulated FWU represented 1.6% of the total annual transpiration of grasses and shrubs in this ecosystem. Despite this low FWU integrated over time compared to transpiration, wetting leaves surfaces can help to avoid larger water deficit during the dry season.