The results support the Remote Sensing and Signaling Theory, which describes how „drug” transporters help optimize levels of metabolites and signaling molecules by facilitating organ crosstalk. Since OAT1 and OAT3 are inhibited by many drugs, the data implies potential for drug-metabolite interactions (DMI). Indeed, treatment of humans with probenecid, an OAT-inhibitor used to treat gout, elevated circulating tryptophan metabolites. Furthermore, given that regulatory agencies have recommended drugs be tested for OAT1 and OAT3 binding or transport, it follows these metabolites can be used as endogenous biomarkers to determine if drug candidates interact with OAT1 and/or OAT3.PorX/PorY is a two-component system (TCS) of Porphyromonas gingivalis that governs transcription of numerous genes including those encoding a type IX secretion system (T9SS) for gingipain secretion and heme accumulation. Here, an in vitro analysis showed that the response regulator PorX specifically bound to two regions in the promoter of porT, a known PorX-regulated T9SS gene, thus demonstrating that PorX/PorY can directly regulate specific target genes. A truncated PorX protein containing the N-terminal receiver and effector domains retained a wild-type ability in both transcription regulation and heme accumulation, ruling out the role of the C-terminal ALP domain in gene regulation. The PorX/PorY system was the only TCS essential for heme accumulation and concomitantly responded to hemin to stimulate transcription of several known PorX-dependent genes in a concentration-dependent manner. We found that PorX/PorY activated the sigH gene, which encodes a sigma factor known for P. gingivalis adaptation to hydrogen peroxide (H2O2). Consistently, both ΔporX and ΔsigH mutants were susceptible to H2O2, suggesting a PorX/PorY-σH regulatory cascade to confer resistance to oxidative stress. Furthermore, the ΔporX mutant became susceptible to high hemin levels that could induce oxidative stress. Therefore, a possible reason why hemin activates PorX/PorY is to confer resistance to hemin-induced oxidative stress. We also demonstrated that PorX/PorY was essential for P. gingivalis virulence because the ΔporX mutant was avirulent in a mouse model. Specifically, this TCS was required for the repression of proinflammatory cytokines secreted by dendritic cells and T cells in the P. gingivalis infected mice.Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen whose virulence is dependent on quorum sensing (QS). DksA1, an RNA polymerase-binding transcriptional regulator, plays a role in determining a number of phenotypes, including QS-mediated virulence. We therefore envisioned that DksA1 inhibitors may help to control P. aeruginosa infection. Here, we screened a library of 6,970 chemical compounds, and identified two compounds (henceforth termed Dkstatins) that specifically suppressed DksA1 activity. Treatment with these two compounds also substantially decreased the production of elastase and pyocyanin, dominant virulence determinants of P. aeruginosa, and protected murine hosts from lethal infection from a prototype strain of P. aeruginosa, PAO1. The Dkstatins also suppressed production of homoserine lactone (HSL)-based autoinducers that activate P. aeruginosa QS. The level of 3-oxo-C12-HSL produced by Dkstatin-treated wildtype PAO1 closely resembled that of the ΔdksA1 mutant. RNA-Seq analysis showed that transcription levels of QS- and virulence-associated genes were markedly reduced in Dkstatin-treated PAO1 cells, indicating that Dkstatin-mediated suppression occurs at the transcriptional level. Importantly, Dkstatins increased the antibiotic susceptibilities of PAO1, particularly to protein synthesis inhibitors, such as tobramycin and tetracycline. Co-immunoprecipitation assays demonstrated that these Dkstatins interfered with DksA1 binding to the β subunit of RNA polymerase, pointing to a potential mechanism of action. Collectively, our results illustrate that inhibition of P. aeruginosa QS may be achieved via DksA1 inhibitors, and that Dkstatins may serve as potential lead compounds to control infection.Mesenchymal stem cell (MSC) administration is a novel and promising therapeutic approach for Alzheimer’s disease (AD). Focusing on an intervention easily translatable into clinical practice, we administered allogeneic bone marrow-derived MSCs intravenously in a mouse model of AD (3xTg-AD). We systematically evaluated the effects of a single-dose and multiple-doses of MSCs in young and old mice (5 or 10 months old), comparing the short-term and long-term effects after 1, 2, or 7 months of treatment. A single dose of MSCs in young mice attenuated neuroinflammation 1 and 7 months after injection, whereas multiple-doses did not show any effect. Multiple-doses of MSCs (administered at 5 to 12 mo, or 10 to 12 mo) reduced the β-secretase cleavage of the amyloid precursor protein, although levels of Aβ-42 did not change. Most interestingly, multiple doses of MSCs affected tau hyperphosphorylation. MSCs administered in young mice for 7 months decreased the pathological tau phosphorylation at T205, S214, and T231. MSCs administered in old mice for 2 months decreased tau phosphorylation at S396. Our findings show how different timing and frequency of MSC injections can affect and modulate several aspects of the AD-like neuropathology in the 3xTg-AD mouse model, strengthening the concept of fine-tuning MSC therapy for Alzheimer’s disease.

Multiple sclerosis (MS) is a neuroinflammatory disease resulting in axonal demyelination and an amalgamation of symptoms which commonly result in decreased quality of life due to mobility dysfunction and limited participation in meaningful activities.

The use of non-invasive brain stimulation (NIBS) techniques, specifically transcranial magnetic and transcranial direct current stimulation, have been essential in understanding the pathophysiological decrements related to disease progression, particularly with regard to motor impairments. Although the research in this area has primarily focused on the upper extremities, new interest has arisen in understanding the neurophysiological underpinnings of lower limb impairment. Therefore, the purpose of this review is to first, provide an overview of common NIBS techniques used to explore sensorimotor neurophysiology; second, summarize lower limb neuromuscular and mobility impairments typically observed in PwMS; third, review the current knowledge regarding interimb impairments associated with neurophysiological adaptations need further evaluation.Infectious spleen and kidney necrosis virus (ISKNV) is a causative agent of high mortality in fish resulting in significant economic loss to the fish industry in many countries. The major capsid protein (MCP) (ORF006) is an important structural component that mediates virus entry into the host cell, therefore it is a good candidate antigen of ISKNV for subunit vaccine development. In this study, MCP of ISKNV was successfully produced in Escherichia coli strain Ril and was purified as the soluble form by refolding recombinant MCP using urea in combination with dialysis process. The refolded recombinant MCP protein had ability of oligomerization to become trimer like native MCP protein. Fish immunized with refolded recombinant MCP showed significantly higher serum antibody titer than fish immunized with insoluble form of the protein (p less then 0.05) at 21, 28- and 35-day post-immunization (dpi). Analysis of immune-related genes response in spleen and kidney of fish immunized with refolded recombinant MCP suggested that MHC-I, MHC-II, IL-1β and IL-4 genes were also significantly expressed relative to the group immunized with insoluble protein (p less then 0.05) at 14, 21, 28- and 35-day post immunization. The highest serum antibody and immune related genes response were found at 28 day post immunization. Therefore, refolded recombinant MCP should be better than previously reported insoluble form as the candidate subunit vaccine to prevent infection of Nile tilapia from ISKNV.This paper is a theoretical study of a protocol for transport of high concentrations of cryoprotectants into biological matter, using isochoric freezing. Unlike isobaric freezing, where the entire system freezes at temperatures lower than the freezing temperature, in isochoric freezing a substantial portion of the system remains unfrozen at temperatures below freezing. In isochoric freezing cryopreservation, the system is designed in such a way that the biological matter remains unfrozen and surrounded by an unfrozen solution. The protocol in this study involves the freezing of an isochoric systems along the „liquidus line” at which water and ice are in thermodynamic equilibrium. Rejection of solutes by ice increases the concentration of the solutes in the unfrozen solution surrounding the unfrozen biological matter, leading, thereby, to transport of increasingly higher concentrations of cryoprotectants into the biological matter, as the temperature of the system is lowered and the toxicity of the cryoprotectants is reduced.Cryopreservation of pancreatic islets can overcome the severe shortage of islet donors in clinical islet transplantation, but the impaired quality of post-warm islets need improvement. This present study was conducted to investigate whether the pre- or post-treatment of rat islets with liver decellularized matrix (LDM) for vitrification can improve the viability (FDA/PI double staining) and the functionality (glucose-stimulated insulin secretion [GSIS] assay). Rat LDM was prepared by high-hydrostatic pressure, lyophilization, and re-suspension in saline. Co-culturing of isolated islets with 0 (control), 30, 60, or 90 μg/ml LDM for 24 h resulted in the comparable viability among the 4 groups (98.7-99.6%) and the higher insulin secretion potential in 30 and 60 μg/ml LDM treatment groups than the control group (stimulation index [SI] 12.1 and 12.7, respectively, vs. 6.5 in the control group, P less then 0.05). When the islets co-cultured with 60 μg/ml LDM were vitrified-warmed on a nylon mesh cryodevice, the viability and the GSIS of the post-warm islets were not improved. Post-treatment of vitrified-warmed islets with 60 μg/ml LDM during the recovery culture for 12 h resulted in the comparable clearance of degenerating cell debris from the post-warm islets, while their insulin secretion potential was improved (SI 5.0 vs. 3.5 in the control group, P less then 0.05). These findings indicate that the components in LDM can enhance the insulin secretion potential of rat islets suffering damage by enzymatic stress during the islet isolation process or by cryoinjuries during the vitrification-warming process.Malaria is an infectious disease reported mostly in the tropical region. The most severe human malaria is Plasmodium falciparum since it can cause cerebral malaria. Therefore, the presence of P. falciparum either in single or mixed infection needs accurate diagnosis. In some mixed infections, the presence of P. falciparum may be cryptic which cannot be detected by microscopic examination. The molecular diagnosis is required in these cases. Many methods based on amplification of malaria parasite genes have been developed but most of them need sophisticated instruments. Here, we created a colorimetric method using probe immobilized gold nanoparticles (AuNPs) to detect the malaria parasite gene. Color changes rely on salt-induced aggregation of AuNPs in the presence or absence of DNA hybridization. Color changes could be observed either by a naked eye or UV-vis spectrophotometer. By this approach, single infection by the most common malaria parasite, P. falciparum or P. vivax could be differentially identified. Mixed infection of these two malaria species could also be clearly diagnosed including cases of cryptic P. falciparum. The novel nanogold based molecular malaria diagnosis is sensitive, specific, rapid and cheap ($0.94). The prepared nanogold malaria probes are stable for up to 3 months indicating their filed application in remote areas.

Obstructive sleep apnea syndrome is a common condition in childhood and if left untreated can result in many health problems. An accurate diagnosis of the etiology is crucial for obstructive sleep apnea treatment success. Functional orthodontic appliances that stimulate mandibular growth by forward mandibular positioning are an alternative therapeutic option in growing patients.

To perform a literature review about the effects of functional orthodontic appliances used to correct the mandibular deficiency in obstructive sleep apnea treatment.

The literature search was conducted in June 2020 using Cochrane Library; PubMed, EBSCO (Dentistry & Oral Sciences Source), LILACS Ovid; SciELO Web of Science; EMBASE Bireme and BBO Bireme electronic databases. The search included papers published in English, until June 2020, whose methodology referred to the types and effects of functional orthopedic appliances on obstructive sleep apnea treatment in children.

The search strategy identified thirteen articles; bsence of control groups, small sample sizes, lack of randomization and no long-term results.

Lysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated.

To investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator.

Diagnostic specimens of 72 patients treated for stage III-IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry.

Lysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014).

Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer.

Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer.

Platinum-based chemotherapeutics play an important role in the treatment of cancer at different levels and are the most cited ototoxic agents when scientific evidence is analyzed.

To present scientific evidence based on a systematic literature review, PRISMA, in order to systematize information on the ototoxic effects of using antineoplastic drugs.

For the selection of studies, the combination based on the Medical Subject Heading Terms (MeSH) was used. The Medline (Pubmed), LILACS, SciELO, SCOPUS, WEB OF SCIENCE and BIREME databases were used, without restriction of language, period, and location. Evaluation of the quality of the articles was carried out, which included articles with a minimum score of 6 in the modified scale of the literature. The designs of the selected studies were descriptive, cohort, and cross-sectional, which were related to the research objective.

Three articles were included in this systematic review. The ototoxicity caused by cisplatin alone varied from 45% to 83.3%, while that caused by the use associated with carboplatin varied from 16.6% to 75%. There was a significant variation in the cumulative doses of these antineoplastic agents, both in isolated and in combination. Auditory changes, especially at high frequencies, were evident after completion of treatment.

Auditory changes after the use of platinum-based antineoplastic drugs were found, however, there was an important heterogeneity regarding the frequency of ototoxicity and the cumulative dose of the drugs used.

Auditory changes after the use of platinum-based antineoplastic drugs were found, however, there was an important heterogeneity regarding the frequency of ototoxicity and the cumulative dose of the drugs used.

The classification of odontogenic tumors has been revised from time to time in order to provide unified terminology. This reclassification had considerable impact on their prevalence and frequency distribution.

This study was aimed to emphasize impact of changing classification systems on prevalence and relative frequency of odontogenic tumors. The secondary objective was to analyze demographics of various histological types of odontogenic tumors in comparison to published literature. Review of Indian studies (1992-2020) elaborating frequency of odontogenic tumors is summarized in the end.

This was a hospital-based retrospective study wherein case files of odontogenic tumors diagnosed from 1990 to 2019 period were retrieved. The classification system used originally at the time of diagnosis was retained and prevalence of odontogenic tumors in three different periods (1990-2004, 2005-2016 and 2017-2019) was compared. Further, prevalence, frequency distribution and demographics of all these tumors (1990-2 and environment influence; however it requires elucidation by further studies.

The continuous evolving systems of classification may partly be responsible for inconsistency in odontogenic tumors, with inclusion of keratocystic odontogenic tumor,and has marked impact on prevalence and frequency distribution of odontogenic tumors. The geographical variations in demographics of odontogenic tumors might reflect genetic and environment influence; however it requires elucidation by further studies.Although advances in osteosarcoma treatment have been made in recent decades, the survival rate for patients suffering from metastatic disease, especially lung metastasis, remains disappointing. Previous studies have confirmed that epithelial-to-mesenchymal transition (EMT) is associated with tumor metastasis, and several studies have suggested that osteosarcoma cells also exhibit EMT-like characteristics. In addition, Notch signaling is known to be related to the development and progression of human malignancies, including osteosarcoma. However, whether chemotherapy affects the EMT-like events and whether these events are medicated by Notch signaling remain to be elucidated. To address these issues, in the current work, osteosarcoma 143B cells were exposed to sublethal concentrations of the first-line chemotherapeutic agent cisplatin (DDP), which promoted cell migration, in vitro invasion, and in vivo lung metastasis. Furthermore, low concentrations of DDP upregulated mesenchymal phenotype-related genes and proteins and promoted EMT-like properties in osteosarcoma cells. In addition, low concentrations of DDP could activate the Notch receptor and its target genes. Finally, combined treatment of DDP with the Notch signaling pathway inhibitor DAPT, which can effectively downregulate mesenchymal phenotype-related genes and proteins, inhibited cell migration and invasion in vitro, and it decreased pulmonary metastatic nodules in vivo. The results of the current study supported the idea that low concentrations of DDP could induce EMT-like characteristics in osteosarcoma cells and could promote cell mobility in vitro, as well as pulmonary metastasis in vivo. Importantly, however, these biological processes are mediated by the Notch signaling pathway. Blocking the Notch signaling pathway can effectively attenuate the osteosarcoma EMT-like phenotype and its associated migration, invasion, and metastasis.Nitrification is a key step in biological nitrogen transformation which depends on the performance of specialized microorganisms. Generally, nitrifying bacteria present a low growth rate and performance which can be improved when immobilized as a biofilm. The development of new materials suitable for the immobilization of nitrifying microorganisms is very important in nitrification and wastewater treatment. In this study, the effect of eggshell powder on biofilm formation by Nitrosomonas europaea an ammonium-oxidizing bacteria and Nitrobacter vulgaris a nitrite-oxidizing bacteria, on new polymeric supports were analyzed. Polylactic acid, polyvinyl chloride and polystyrene were tested to produce polymer-eggshells powder composites and used as biofilm supports for nitrifying bacteria. The support material was characterized to identify the most suitable polymer-eggshells powder combination for the cell adhesion and biofilm formation. The nitrification results showed a highest nitrate production of 42 mg NO3–N/L with polylactic acid-eggshell composite, with the best surface properties for cellular adhesion. Finally, scanning electron microscopy micrographs confirmed the best biofilm formed on polylactic acid-eggshell.

Pregnant women’s stress, mental and physical health, and health behaviours can have important implications for maternal and child health outcomes.

To examine pregnant women’s levels of stress, mental and physical health, and health behaviours during the COVID-19 pandemic.

A cross-sectional survey was conducted online, with recruitment and data collection occurring between 16/6/20 and 17/7/20. Participants were pregnant women recruited via online pregnancy/parenting communities. Participants self-reported their levels of general stress, pregnancy-specific stress and COVID-19 related stress, mental and physical health, general health behaviours, and COVID-19 related health behaviours.

573 pregnant women participated in the survey. Participants were most commonly resident in the United States (42.6%, n=243), Ireland (41.2%, n=235) or the United Kingdom (10%, n=57). The majority (80.0%, n=457) were married and educated to degree level or above (79.3, n=453). Pregnant women reported high levels of pregnancy-specific and COVID-19-related stress, and low levels of mental and physical health, during the pandemic. Encouragingly, pregnant women in this study generally reported high levels of adherence to public health advice and pregnancy health behaviours. Stress and general mental health outcomes were best predicted by well-being factors (including stress and social support). Health impairing behaviours (e.g. poor diet) were predicted by both well-being and demographic factors.

Interventions targeting pregnancy- and pandemic-specific stress at the population level will be essential to support mental health and minimise adverse outcomes for women and children during the pandemic.

Interventions targeting pregnancy- and pandemic-specific stress at the population level will be essential to support mental health and minimise adverse outcomes for women and children during the pandemic.

The aim of this study was to analyze risk factors for failure of subclavian vein catheterization.

A retrospective analysis of 1562 patients who underwent subclavian vein puncture performed by the same experienced operator at Peking University Cancer Hospital from January 1, 2016 to January 1, 2019 was conducted. The success or failure of subclavian vein catheterization was registered in all cases. Various patient characteristics, including age, gender, body mass index (BMI), preoperative hemoglobin, preoperative hematocrit, preoperative mean corpuscular hemoglobin concentration (MCHC), preoperative albumin, preoperative serum creatinine, puncture needles from different manufacturers and previous history of subclavian vein catheterization were assessed via univariate and multivariate analyses.

For the included patients, landmark-guided subclavian vein puncture was successful in 1476 cases and unsuccessful in 86 cases (success rate of 94.5%). Successful subclavian vein catheterization was achieved via right and left subclavian vein puncture in 1392 and 84 cases, respectively. In univariate analyses, age and preoperative hemoglobin were associated with failure of subclavian vein catheterization. In a multivariate analysis, aged more than 60 years was a risk factor while the central venous access with Certofix® was associated with an increased rate of success (p-values of 0.001 and 0.015, respectively).

This study has demonstrated that patient aged more than 60 years was a risk factor for failure of subclavian vein catheterization while the central venous access with Certofix® was associated with an increased rate of success.

This study has demonstrated that patient aged more than 60 years was a risk factor for failure of subclavian vein catheterization while the central venous access with Certofix® was associated with an increased rate of success.Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.

Contemporary literature suggests a similar transverse stability of a surgical-assisted rapid palatal expansion and a segmented Le Fort I osteotomy. The aim of this study was to compare postoperative complications of 1-stage (segmental maxillary osteotomy) and 2-stage (surgical-assisted rapid palatal expansion followed by Le Fort I osteotomy) treated patients to determine the preferred treatment strategy.

This retrospective study included 74 consecutive patients (age range 14 – 57years; 36 males, 38 females) with a moderate transverse maxillary hypoplasia 32 patients were treated in a 1-stage protocol and 42 in a 2-stage protocol with a postoperative follow-up of at least 1year. Dental complications such as loss of teeth, gingival dehiscence, periodontal bone loss, apical root resorption, and surgical complications such as pain, hemorrhage, altered neurosensitivity, wound infection, aseptic necrosis were analyzed. Univariate analysis consisted of a generalized linear model with logit link or Fisher exact test.

No significant difference was found for group characteristics except for longer orthodontic treatment time in the 2-stage group. Incidence and severity of complications were comparable for the 1-stage and 2-stage patients. Only overall pain was significantly greater in the 2-stage patient group (P=.038).

Considering a similar complication rate and transversal stability, the choice between 1-stage and 2-stage approach for patients with a moderate transverse maxillary hypoplasia should be patient specific.

Considering a similar complication rate and transversal stability, the choice between 1-stage and 2-stage approach for patients with a moderate transverse maxillary hypoplasia should be patient specific.

This study was conducted to ascertain the efficacy of buccal injection of articaine compared to lidocaine in inducing palatal anesthesia in different maxillary regions.

This double-blinded, randomized clinical trial included 300 patients who referred for extraction of 1 maxillary tooth. The patients were categorized into 3 strata according to the extraction area (anterior, premolar, molar), and then randomly assigned to 2 groups based on the administered medication. The first group received buccal infiltration by 0.6mL of 2% lidocaine, whereas the second group was buccally administered using 0.6mL of 4% articaine. After a waiting period of 2minutes, the failure or success in achieving palatal anesthesia was assessed by the instrumentation technique. In cases of failed anesthesia, an additional 0.6mL of the same anesthetic was given, and the procedure was repeated if palatal anesthesia was not attained after a 2-minute delay. If pain remained 2minutes after the third injection, a supplemental palatal infiltration was administered and the extraction was attempted.

The success rate of buccal infiltration in achieving palatal anesthesia was 82.7% in the articaine group and 1.3% in the lidocaine group. There was a significant difference in the success rate and drug volume required to induce palatal anesthesia between the 2 groups (P<.001), but no significant difference was found between different maxillary regions, using either of the medications (P>.05).

Articaine can be considered as a suitable alternative to lidocaine for eliminating painful palatal infiltration in the extraction of maxillary teeth.

Articaine can be considered as a suitable alternative to lidocaine for eliminating painful palatal infiltration in the extraction of maxillary teeth.

This article describes the induced membrane technique (IMT) and presents 10 cases in which the technique was applied for segmental mandibular reconstruction.

Ten patients requiring segmental mandibular resection were reconstructed using the staged IMT. Mandibular resection, placement of a reconstruction plate and polymethylmethacrylate spacer, was performed. At the second procedure, the spacer was removed through a small incision and particulate autograft from the ilium was placed, in some cases with bone morphogenic protein.

Nine of the 10 patients achieved bony continuity with the IMT. Spacers were designed to optimize mandibular form and future implant-based restoration. All patients have either had implants placed or have adequate bone for implant placement. The average hospital length of stay for both surgeries combined was 3.1 nights.

The IMT can be successfully used to reconstruct segmental mandibular defects, allowing surgeons to create a neomandible with optimal form both for facial contour and for dental implant-based reconstruction.

The IMT can be successfully used to reconstruct segmental mandibular defects, allowing surgeons to create a neomandible with optimal form both for facial contour and for dental implant-based reconstruction.Traumatic genial tubercle fracture of the mandible is a rare event that may cause airway compromise owing to loss of the support to the base of the tongue. Over the last 70 years, only 7 known cases of traumatic genial tubercle fractures have been reported. We detail the surgical management of 2 traumatically induced genial tubercle fractures that involved varying levels of airway compromise. These 2 cases add to the limited body of knowledge of the surgical management of this rare and potentially fatal mandible fracture pattern.

The aim of this study was to investigate the effects of traditional thermoplastic splints vs a 3D-printed custom external nasal splint designed to apply pressure to the lateral osteotomy lines and neighboring periorbital region on edema and ecchymosis after rhinoplasty.

Forty patients undergoing open rhinoplasty were included in this prospective randomized controlled study. The patients were divided into 2 groups. In the study group, the new 3D-printed custom external nasal splint was used. In the control group, the thermoplastic external nasal splint was used. Periorbital edema and ecchymosis scores were assessed peroperative before external nasal splint application, postoperatively at the 1st and 4th hours, and 1st, 2nd, 5th, 7th, 10th, and 15th days.

There were lower scores of ecchymosis and edema in the study group compared to the control group for all the follow-up controls. There was a significant difference between the 2 groups with respect to the occurrence of ecchymosis for all follow-up controls except for the first postoperative hour and the seventh postoperative day (P<.05). Comparison of the 2 groups with respect to the grade of edema showed a significant difference only in the first and fourth postoperative hours (P<.05).

The study detected less edema and ecchymosis scores using this 3D custom external nasal splint, thus creating a new area of use for 3D printers in the field of facial esthetic surgery. New thermoplastic splints of different shapes and sizes can be produced that can compress the osteotomy lines and the neighboring periorbital region.

The study detected less edema and ecchymosis scores using this 3D custom external nasal splint, thus creating a new area of use for 3D printers in the field of facial esthetic surgery. New thermoplastic splints of different shapes and sizes can be produced that can compress the osteotomy lines and the neighboring periorbital region.

Previous retrospective studies demonstrate that urgent evaluation by an ophthalmologist for orbital fractures is not required in visually asymptomatic patients, although a consult is often seen as a necessity in many hospital institutions. To determine when an ophthalmology consult is indicated for a surgical patient, the oral and maxillofacial and ophthalmology departments at 1 institution collaborated for an evidence-based approach utilizing retrospective and prospective data.

The retrospective arm looked at patients from 2012 to 2017, who had an isolated, surgically repaired orbital fracture without preoperative ophthalmology consultation. A prospective arm was then created from August 2019 to July 2020 with a designed protocol that determined which patients required an ophthalmology consult preoperatively. Extra-ocular movements, visual acuity, and diplopia were examined in the preoperative and postoperative setting to determine if the lack of an ophthalmology consult adversely affected patient outcome.

Of the retrospective patients who met criteria, 82 of the 84 (98%) patients had a normal postoperative examination baseline visual acuity, intact extra-ocular movement, and no diplopia. The 2 of the 84 (2%) patients had postoperative diplopia consistent with preop examination. In the prospective group, 10 of the 39 patients required a preop ophthalmology consult while 29 of 39 did not require one. A normal postoperative examination was present in 26 of the 29 patients (90%). Of those 3 remaining patients, 2 patients (7%) had postoperative diplopia consistent with preoperative while 1 patient (3%) had postoperative diplopia without preoperative diplopia.

The authors conclude that a routine ophthalmology consult is not warranted in visually asymptomatic patients with orbital fractures requiring surgical repair.

The authors conclude that a routine ophthalmology consult is not warranted in visually asymptomatic patients with orbital fractures requiring surgical repair.Emergency medical assistance is rare when concerning air travel. Pulmonary barotrauma during air travel can occur in asymptomatic patients who have underlying intra-parenchymal pulmonary pathology such as bullae or bronchogenic cysts. During aircraft travel, the resultant decrease in pressure during the ascent can lead to expansion of the cyst volume culminating in tears and leakage of air into the surrounding vasculature and thus potential for air embolism. We describe a case of massive cerebral air embolism secondary to pulmonary barotrauma in a previously asymptomatic patient.This report describes a 36-year-old woman with multiple gastric gastrointestinal stromal tumors, hepatic and lymphatic metastasis, and a mediastinal paraganglioma as a presentation of an incomplete Carney triad. Our purpose is to present our therapeutic approach, with emphasis on the surgical and oncological specificities of this syndrome.

The aim of this study was to investigate the effect of various predictors on burnout among radiology residents during their training.

In this cross-sectional analysis, we distributed the Maslach Burnout Index for Medical Personnel (MBI-HSS [MP]) to eligible United States (US) radiology residents. Covariates of interest included age, child status, debt burden, partner status, and self-identified gender. Primary outcomes include MBI-HSS (MP) subcomponent scores – emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Mann-Whitney tests were used to compare averages between groups.

Out of the 770 of 2823 residents (27.3%) who responded, 488 of 770 completed the MBI-HSS (MP). During the R1 year, male sex was associated with marginally higher PA scores (36.5 versus 33.5; P = .029). Having children or a partner was associated with lower EE scores (18.7 versus 26.8, P = .012; 22 versus 28.9, P = .022, respectively) and higher PA scores (37 vs 32.7, P = .024; 35 versus 31.3, P = .039, respectively) among the R3 cohort. Reporting debt < $200,000 was associated with lower EE scores among the R3 (21.2 versus 27.3, P = .028) and R4 (16.4 versus 21.9, P = .033) cohort.

There are several predictors of burnout that transiently impact residents at different years of training and primarily impact EE or PA, but not DP scores. R3 residents’ scores are most sensitive to these covariates.

There are several predictors of burnout that transiently impact residents at different years of training and primarily impact EE or PA, but not DP scores. R3 residents’ scores are most sensitive to these covariates.

There have been substantial changes in the management of patients with metastatic renal cell carcinoma (mRCC) over the past decade, with upfront immunotherapy-based combinations replacing targeted therapies. A broad range of combinations have been approved, and comparisons of their efficacy and safety are needed to guide the optimal choice of first-line therapy.

To perform indirect comparisons of efficacy and safety of first-line immune checkpoint inhibitor (ICI)-based combination therapies for mRCC.

We searched multiple databases and abstracts of major scientific meetings up to February 2021 to identify phase III randomized controlled trials of patients receiving first-line ICI-based combination therapies for mRCC. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included complete response rates (CRRs), objective response rates (ORRs), grade ≥3 treatment-related adverse events (TRAEs), and rates of treatment discontinuation due to adverse evephysicians and patients to select the appropriate treatment strategy.

Discrepancies exist between patient-reported storage phase symptoms severity and International Prostate Symptom Score (IPSS) scores.

To investigate whether the Overactive Bladder questionnaire (OABq) can detect further storage phase lower urinary tract symptoms (LUTS) among patients complaining solely of voiding LUTS based on the IPSS questionnaire, and to address the real-life impact of voiding LUTS towards patients’ quality of life (QoL).

Data from 233 consecutive men seeking medical help for LUTS/benign prostate enlargement for the first time were analysed. All patients completed both the OABq and the IPSS questionnaire. In order to investigate patients with predominantly voiding phase symptoms, men with storage phase symptoms at IPSS were eventually excluded from the analysis. Patients with an OABq score of ≥40 were considered as those having moderate-to-severe storage LUTS.

Descriptive statistics and linear regression models tested the associations between OABq scores, IPSS, and IPSS-QoL.

OABq wer urinary tract symptoms (LUTS) in patients presenting solely with voiding LUTS according to the IPSS questionnaire. Moreover, the OABq is associated with worse quality of life in these patients regardless of the severity of voiding symptoms.

The Overactive Bladder questionnaire (OABq) is able to detect the presence of additional storage lower urinary tract symptoms (LUTS) in patients presenting solely with voiding LUTS according to the IPSS questionnaire. Moreover, the OABq is associated with worse quality of life in these patients regardless of the severity of voiding symptoms.

The Oncotype DX assay is a clinically validated 17-gene genomic assay that provides a genomic prostate score (GPS; scale 0-100) measuring the heterogeneous nature of prostate tumors. The test is performed on prostate tissue collected during biopsy. There is a lack of data on the association between the GPS and tumor pathology after radical prostatectomy (RP).

To investigate the association between GPS and final pathology, including extraprostatic extension (EPE), positive surgical margin (PSM), and seminal vesicle invasion (SVI).

Data for the 749 patients who underwent Oncotype DX assay and RP at a referral prostate cancer center between 2015 and 2019 were retrospectively assessed to evaluate the association between GPS and unfavorable pathology parameters.

After a GPS genetic test, patients underwent robotic RP performed by the same surgeon.

Multivariable logistic regression analyses were performed to assess the association between GPS and EPE, PSM, and SVI. The models were adjusted for age, clinichological features.

We studied whether the score for a prostate genetic test was associated with prostate cancer pathology findings for patients who had their prostate removed. We found that the risk of prostate cancer spread outside the gland and to the seminal vesicle increases with higher test scores. These findings may help surgeons in counseling patients on surgical options for prostate cancer.

We studied whether the score for a prostate genetic test was associated with prostate cancer pathology findings for patients who had their prostate removed. We found that the risk of prostate cancer spread outside the gland and to the seminal vesicle increases with higher test scores. These findings may help surgeons in counseling patients on surgical options for prostate cancer.Long-chain fatty acid oxidation is frequently impaired in primary and systemic metabolic diseases affecting the heart; thus, therapeutically increasing reliance on normally minor energetic substrates, such as ketones and medium-chain fatty acids, could benefit cardiac health. However, the molecular fundamentals of this therapy are not fully known. Here, we explored the ability of octanoate, an eight-carbon medium-chain fatty acid known as an unregulated mitochondrial energetic substrate, to ameliorate cardiac hypertrophy in long-chain fatty acid oxidation-deficient hearts because of carnitine palmitoyltransferase 2 deletion (Cpt2M-/-). CPT2 converts acylcarnitines to acyl-CoAs in the mitochondrial matrix for oxidative bioenergetic metabolism. In Cpt2M-/- mice, high octanoate-ketogenic diet failed to alleviate myocardial hypertrophy, dysfunction, and acylcarnitine accumulation suggesting that this alternative substrate is not sufficiently compensatory for energy provision. Aligning this outcome, we identified a major metabolic distinction between muscles and liver, wherein heart and skeletal muscle mitochondria were unable to oxidize free octanoate, but liver was able to oxidize free octanoate. Liver mitochondria, but not heart or muscle, highly expressed medium-chain acyl-CoA synthetases, potentially enabling octanoate activation for oxidation and circumventing acylcarnitine shuttling. Conversely, octanoylcarnitine was oxidized by liver, skeletal muscle, and heart, with rates in heart 4-fold greater than liver and, in muscles, was not dependent upon CPT2. Together, these data suggest that dietary octanoate cannot rescue CPT2-deficient cardiac disease. These data also suggest the existence of tissue-specific mechanisms for octanoate oxidative metabolism, with liver being independent of free carnitine availability, whereas cardiac and skeletal muscles depend on carnitine but not on CPT2.

The relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP.

The aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP.

This was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model.

Before diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P<0.001), harboring the SPINK1 mutation(P<0.001), diabetes(P<0.001) and steatorrhea(P<0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P<0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors.

SPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.

SPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.

The Foot and Ankle Outcome Score (FAOS) is one of the most frequently used patient-reported outcome measures for foot and ankle conditions. The aim is to test the structural validity of the Finnish version of the FAOS using Rasch Measurement Theory.

FAOS scores were obtained from 218 consecutive patients who received operative treatment for foot and ankle conditions. The FAOS data were fitted into the Rasch model and person separation index (PSI) calculated.

All the five subscales provided good coverage and targeting. Three subscales presented unidimensional structure. Thirty-eight of the 42 items had ordered response category thresholds. Three of the 42 items had differential item functioning towards gender. All subscales showed sufficient fit to the Rasch model. PSI ranged from 0.73 to 0.94 for the subscales.

The Finnish version of the FAOS shows acceptable structural validity for assessing complaints in orthopaedic foot and ankle patients.

The Finnish version of the FAOS shows acceptable structural validity for assessing complaints in orthopaedic foot and ankle patients.End stage ankle joint arthritis is a debilitating condition. Surgical treatment, most commonly ankle arthrodesis or fusion, can be highly effective. The authors outline the nature and prevalence of ankle arthritis and show that the frequency of each type of procedure varies geographically. They present data supporting the hypothesis that units performing ankle replacement more frequently tend to have better outcomes, both clinically and financially. Adoption of country-wide Ankle Arthritis Networks is proposed, ensuring that every patient seeing a foot and ankle orthopaedic surgeon has potential access to all treatment options whether their surgeon chooses to perform replacement or not. The case is made that establishment of Ankle Arthritis Networks will avoid the need for units to perform a low number of replacements per year, homogenise treatment availability across the country and enables the right patient to receive the right treatment first time. LEVEL OF EVIDENCE IV.Diagnostic Reference Levels (DRLs) is an important tool that can improve radiation safety in medical imaging. However, there are certain aspects that need improvement and several obstacles that should be overcome before DRLs are fully implemented in practice. It is the authors belief that DRLs should be a dynamic tool that follows the development of clinical practice and technology advances. The establishment of adult and paediatric DRLs based on clinical indications should be considered as a priority. A common methodology and terminology is needed to allow for their clinical use. Dose monitoring systems can improve and accelerate the establishment, update and use of DRLs. However, certain steps need to be taken for proper collection. organization and analysis of big data. Availability of clinically qualified medical physicists in medical imaging departments, awareness on the importance of dose optimization and proper cooperation of relevant stakeholders are important prerequisites for the successful establishment and use of DRLs.

To implement the use of standardized preoperative briefings and postoperative debriefings for surgical cases involving residents in an effort to improve resident autonomy and skill acquisition.

Prospective longitudinal study.

Johns Hopkins Department of Otolaryngology-Head and Neck Surgery.

Resident and attending physicians.

Joint Huddles for Improving Resident Education (JHFIRE) tool was created and successfully implemented by 19 residents and 17 faculty members. Over the course of three data collection periods spanning an academic year, overall scores improved though not statistically significantly in the metrics of Zwisch autonomy, Resident Performance, and Objective Structured Assessment of Technical Skills (OSATS) scores. Female residents were scored significantly higher by attendings than their male counterparts in the assessment of baseline Resident Performance.

(1) JHFIRE tool implemented a standardized preoperative briefing and postoperative debriefing to improve communication and resident skill acquisition; (2) The tool was accepted and utilized throughout an academic year; (3) Zwisch, Resident Performance, and OSATS scores improved though not significantly.

(1) JHFIRE tool implemented a standardized preoperative briefing and postoperative debriefing to improve communication and resident skill acquisition; (2) The tool was accepted and utilized throughout an academic year; (3) Zwisch, Resident Performance, and OSATS scores improved though not significantly.

Institutionalized older adults have a high prevalence of frailty and disability, which may make them more vulnerable to the negative consequences of coronavirus disease 2019 (COVID-19). We investigated the impact of COVID-19 on the level of frailty, physical, and cognitive performance in nursing home residents.

Nested case-control study.

The study included nursing home residents who were infected with COVID-19 (case group, n=76), matched by age to a control group (n=76).

Participants’ sociodemographic and medical data were collected, and they were also assessed for physical function (handgrip and walking speed), cognitive performance (Mini-Mental State Examination) and frailty (Frail-NH scale) before the first wave of the COVID-19 pandemic (October to December 2019, pre-COVID-19) and after (June to July 2020, post-COVID-19). COVID-19 symptoms and clinical course were recorded for the cases.

Between the pre- and post-COVID-19 assessments, we found a 19% greater deterioration in handgrip, a 22% greater decrease in walking speed, and a 21% greater increase in Frail-NH scores in cases compared with controls.