New concept: "TARN friendly trauma reporting" (what radiologists say really does matter).

AIM: To establish if detailed review of trauma reports with reference to coding manual improved accuracy of ISS and to establish if demonstrated changes in coding affected performance and tariff payment. MATERIALS AND METHODS: A study was undertaken which gathered data from 6 months across the five trusts with information on imaging undertaken, mechanism of injury (MOI), Injury Severity Score (ISS), and injury descriptors was included. Patients with ISS near to a best practice tariff boundary of 9 and 16 (5-8 and 11-15) then had their imaging reviewed by the Radiology Department with direct reference to the ISS coding manual. Injuries were then re-coded and ISS recalculated. RESULTS: Over the 6-month period, 1,693 patients were admitted to the database from the five hospitals. One hundred and sixty-nine (9.9%) patients met the inclusion criteria for review. Thirty-five (20.7%) had a change in abbreviated (region specific) injury code, with 30 a change in the resultant ISS. Three had a decrease in ISS and 27 increased ISS with all 27 moving across an ISS best practice tariff and three moving across two payment tariff boundaries. With re-coding, there was a potential £15,000 of lost revenue from the major trauma centre (MTC) alone. CONCLUSION: Reporting with reference to ISS description improves the accuracy of ISS significantly. Radiologists improving the descriptions of specific injury patterns and adopting 'Trauma Audit and Research Network friendly' reporting strategies may improve data accuracy, performance, and payment of best practice tariffs to hospitals.

Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration.

INTRODUCTION: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans. RESULTS: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates. DISCUSSION: Active lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Understanding breast cancer screening--past, present, and future.

This article provides an up-to-date overview of breast cancer mammography screening and briefly discusses its history, controversies, current guidelines, practices across Asia, and future directions. An emphasis is made on shared decision-making--instead of giving just a 'yes' or 'no' answer to patients, the focus should be on providing sufficient information about the pros and cons of screening to help women make a personal, informed choice. Frontline experts, including breast surgeons, oncologists, breast radiologists, and their representative professional associations should all participate in guideline panels, with the goal of improving cancer detection, reducing mortality, and improving patient outcome.

Clinical audit training improves undergraduates' performance in root canal therapy.

AIM: To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. METHODS: Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. RESULTS: Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). CONCLUSION: Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT.

An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong.

OBJECTIVE: New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong. PARTICIPANTS: Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society. EVIDENCE: A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution. CONSENSUS PROCESS: Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature. CONCLUSIONS: Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

Polymicrobial bacterial or fungal infections: incidence, spectrum of infection, risk factors, and clinical outcomes from a large hematopoietic stem cell transplant center.

BACKGROUND: Infections cause significant morbidity and mortality for patients who undergo hematopoietic stem cell transplantation (HSCT). Cancer patients who develop polymicrobial infection (PI) are at increased risk for poor clinical outcomes, yet very limited data have been published within the HSCT setting. METHODS: An observational study of 901 stem cell transplant recipients was conducted at Northwestern Memorial Hospital to identify the incidence, risk factors and outcomes for HSCT recipients who develop infection(s) with multiple bacterial or fungal organisms. RESULTS: Among 901 HSCT recipients reviewed (675 autografts and 226 allografts), 237 patients (27%) had microbiologically documented microorganisms isolated, including 179 patients (76%) with monomicrobial infection and 59 patients (24%) with multiple microorganisms, of which 34 (14%) were classified as PI, and 25 (10%) as multiple distinct episodes of infection. CONCLUSION: The results show co-infection with multiple organisms during HSCT is relatively rare; however, these patients are at an increased risk for the development of acute graft-versus-host disease, delayed engraftment, and overall mortality.

Amphotericin B deoxycholate nasal spray administered to hematopoietic stem cell recipients with prior fungal colonization of the upper airway passages is associated with low rates of invasive fungal infection.

BACKGROUND: Invasive fungal infections cause major problems during hematopoietic stem cell transplantation (HSCT). Fungal colonization of the upper airway passages occurs frequently, and may serve as a portal of entry for potentially life-threatening fungal infections, especially in immunocompromised patients. METHODS: A clinical practice was instituted at Northwestern Memorial Hospital in Chicago in 2005, to administer amphotericin B deoxycholate nasal spray (ABNS) 0.5% to all HSCT recipients with fungal colonization of their nasal passages, in addition to standard oral antifungal prophylaxis. RESULTS: Among 1945 HSCT patients treated during the study period, 109 patients were identified with positive fungal surveillance cultures. CONCLUSION: Breakthrough fungal infections occurred in only 2 patients (2%), thus in this select group of HSCT recipients, ABNS administration is associated with a very low rate of breakthrough infection.

Deletion of MAP2K2/MEK2: a novel mechanism for a RASopathy?

RASopathies are a class of genetic syndromes caused by germline mutations in genes encoding Ras/mitogen-activated protein kinase (Ras/MAPK) pathway components. Cardio-facio-cutaneous (CFC) syndrome is a RASopathy characterized by distinctive craniofacial features, skin and hair abnormalities, and congenital heart defects caused by activating mutations of BRAF, MEK1, MEK2, and KRAS. We define the phenotype of seven patients with de novo deletions of chromosome 19p13.3 including MEK2; they present with a distinct phenotype but have overlapping features with CFC syndrome. Phenotypic features of all seven patients include tall forehead, thick nasal tip, underdeveloped cheekbones, long midface, sinuous upper vermilion border, tall chin, angular jaw, and facial asymmetry. Patients also have developmental delay, hypotonia, heart abnormalities, failure to thrive, obstructive sleep apnea, gastroesophageal reflux and integument abnormalities. Analysis of epidermal growth factor-stimulated fibroblasts revealed that P-MEK1/2 was ∼50% less abundant in cells carrying the MEK2 deletion compared to the control. Significant differences in total MEK2 and Sprouty1 abundance were also observed. Our cohort of seven individuals with MEK2 deletions has overlapping features associated with RASopathies. This is the first report suggesting that, in addition to activating mutations, MEK2 haploinsufficiency can lead to dysregulation of the MAPK pathway.

Synergistic induction of interleukin-6 expression by endothelin-1 and cyclic AMP in adipocytes.

BACKGROUND: We have demonstrated previously that endothelin-1 (ET-1) may stimulate interleukin-6 (IL-6) release from 3T3-L1 adipocytes. In this study, we further examined the combined effect of ET-1 and cyclic adenosine monophosphate (cAMP) on IL-6 release. METHODS: IL-6 release was measured by enzyme-linked immuosorbent assay. Reverse transcriptase-PCR and real-time PCR analyses were used to determine cellular mRNA levels. A luciferase reporter driven by promoter (-1310/+198) of mouse IL-6 gene was transfected into 3T3-L1 adipocytes to monitor IL-6 transcription. RESULTS: ET-1 and cAMP induced IL-6 release in a synergistic manner that can be attributed to their synergistic induction of IL-6 gene expression, as evidenced by IL-6 mRNA analysis and the IL-6 promoter reporter assay. Both ET(A) and ET(B) receptors seem to be involved. In addition, enhanced IL-6 promoter activity can be similarly induced by ET-1 and catecholamines (epinephrine and norepinephrine). The cooperative interaction between ET-1 and cAMP on IL-6 expression seems distinctive, as no other proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and IL-1ß, are similarly affected. In fact, cAMP inhibited ET-1-stimulated TNF-α and IL-1ß expressions in adipocytes. Furthermore, injection of mice with epinephrine and ET-1 induced a tremendously synergistic increase in serum IL-6 levels. Nevertheless, whereas cAMP induced IL-6 expression in RAW264.7 mouse macrophages, ET-1 had no effect on either the basal or the cAMP-induced IL-6 expression. CONCLUSION: ET-1 and epinephrine may boost plasma IL-6 levels in mice in a synergistic manner, probably through their synergistic induction of IL-6 expression in adipocytes. SIGNIFICANCE: This study should provide a new perspective for treating IL-6-related diseases, especially those accompanied with elevated ET-1 and catecholamine levels.

Cross-sectional assessment of pain and physical function in skeletal dysplasia patients.

Short stature skeletal dysplasia (SD) patients have orthopedic and neurologic complications causing significant pain and physical disability. We conducted a large cross-sectional online survey in 361 people with short stature SD (>10 years) to describe pain prevalence, characteristics, and the relationship between pain and function. Chronic pain prevalence per Brief Pain Inventory (BPI) was 70.3%. Women reported more pain than men (73% vs 63% p = 0.04). Pain Severity Score (average of current, worst, least and average pain) averaged 3.3 ± 2, while the Pain Interference Score (with daily activities) averaged 3.4 ± 2.7 on a 10-point scale. Per Bleck scale, 20.5% had little or no functional capacity. Increasing age and decreased ambulation independently predicted chronic pain. Chronic pain is prevalent in short stature SD patients and associated with poor physical function. Further study is required to clarify the temporal relationship among pain, function and treatments.

Tapachula-7, a new genetic sexing strain of the Mexican fruit fly (Diptera: Tephritidae): sexual compatibility and competitiveness.

A new genetic sexing strain of the Mexican fruit fly, Anastrepha ludens (Loew), was evaluated in tests of sexual behavior to determine its possible application using the sterile insect technique. Tests in field cages measuring time to sexual maturity, compatibility with wild flies, and competitiveness were compared between the genetic sexing strain, Tapachula-7, and the mass-reared standard bisexual strain. The results indicated that the onset of sexual maturity was similar for both laboratory strains. Males from the Tapachula-7 strain do not differ from the standard bisexual strain in compatibility and competitiveness with wild insects. The results indicate that the release of Tapachula-7 males in the field would be viable in programs that use the sterile insect technique for the control of the Mexican fruit fly.

Diagnostic and treatment preferences for cracked posterior teeth.

BACKGROUND: Longitudinal cracks in teeth are common and often present challenges in diagnosis and management. This study investigated the preferred diagnostic process and treatment modalities for these cracked teeth. METHODS: Dentists currently registered with Dental Board of Australia and practising within Australia were invited to complete an online Qualtrics-based survey on their perspectives on the presentations, diagnosis, and treatment preferences for cracked teeth. RESULTS: Of respondents, 56.8% chose to place an indirect cuspal-coverage restoration on an asymptomatic cracked vital tooth. When the tooth was mildly cold sensitive, direct cuspal-coverage restoration was favoured (64.9%), while 36.8% preferred placing an orthodontic band in a tooth with biting pain. Respondents had higher odds of recommending indirect restoration when CAD-CAM milling was available on-site or magnification was routinely used, regardless of presenting symptoms. Almost half (46.8%) preferred to extract if the tooth undergoing root canal treatment had a crack with a 5 mm probing pocket depth. Most (71.4%) demonstrated a poor understanding of cracked tooth biomechanics. CONCLUSION: Australian dentists varied in their diagnostic and treatment preferences for cracked teeth, reflecting a need for more well-controlled clinical studies in the diagnostic process, clinical biomechanics and treatment modalities for these teeth. © 2023 Australian Dental Association.

Global Cross-Sectional Study Evaluating the Attitudes towards a COVID-19 Vaccine in Pregnant and Postpartum Women.

Pregnant and postpartum women have an increased risk of severe complications from COVID-19. Many clinical guidelines recommend vaccination of these populations, and it is therefore critical to understand their attitudes toward COVID-19 vaccines. We conducted a cross-sectional online survey in November 2020 of currently pregnant and ≤1-year postpartum women in Brazil, India, the United Kingdom (UK), and the United States (US) that assessed their openness to COVID-19 vaccines and reasons for vaccine hesitancy. Logistic regression analyses were conducted to evaluate openness to receiving a vaccine. Out of 2010 respondents, 67% were open to receiving a COVID-19 vaccine themselves. Among pregnant and postpartum participants, 72% and 57% were willing to receive a vaccine, respectively. Vaccine openness varied significantly by country: India (87%), Brazil (71%), UK (59%), and US (52%). Across all participants, among the 33% who were unsure/not open to receiving a COVID-19 vaccine, the most common reason cited was safety/side effect concerns (51%). Participants were similarly open to their children/other family members receiving a COVID-19 vaccine. Presence of a comorbidity, a positive COVID-19 test result, and pregnancy were all significantly associated with positive vaccine acceptance. Targeted outreach to address pregnant and postpartum women's concerns about the COVID-19 vaccine is needed.

Power-efficient III-V/silicon external cavity DBR lasers.

We report the design and characterization of external-cavity DBR lasers built with a III-V-semiconductor reflective-SOA with spot-size converter edge-coupled to SOI waveguides containing Bragg grating mirrors. The un-cooled lasers have wall-plug-efficiencies of up to 9.5% at powers of 6 mW. The lasers are suitable for making power efficient, hybrid WDM transmitters in a CMOS-compatible SOI optical platform.

Interest in Home Birth During the COVID-19 Pandemic: Analysis of Google Trends Data.

INTRODUCTION: Nearly all (94%-99%) pregnant persons in developed countries search for pregnancy-related information online. The advent of the novel coronavirus disease 2019 (COVID-19) and the associated restrictions in hospital policies may have pushed pregnant persons in the United States to consider giving birth at home to achieve their desired birth experience. METHODS: Google Trends is an open, rich source of real-time, anonymized, relative data on disease patterns and population behavior that provides data in the form of search volume index (SVI): the search volume for a queried term relative to overall search volume for a given time frame and geographic location. The SVI is normalized to a scale of 0 to 100. After the World Health Organization declared COVID-19 a pandemic on March 11, 2020, Google Trends was queried on February 21, 2021, for the search term home birth with location set to the United States and the time frame March 11, 2019 to February 21, 2021. RESULTS: The median SVI for home birth during nominally pre-COVID-19 baseline (weeks of March 17, 2019 to March 8, 2020) was relatively constant at 43 (range, 25-56) and increased sharply to 77 during the week of March 15, to 86 during the week of March 22, and peaked at 100 during the week of March 29, 2020. The SVI declined substantially in the following weeks but remained significantly elevated compared with baseline levels. During the approximate 2-year period of query, the states with the highest SVI values (≥80) were Arkansas, Washington, Montana, and Georgia. DISCUSSION: Interest in home birth spiked in the United States immediately after COVID-19 was declared a pandemic and remained significantly elevated thereafter. These results have implications for caregivers and health systems to ensure safe pregnancies and childbirths through the resolution of the ongoing pandemic.

Mechanical control of cyclic AMP signalling and gene transcription through integrins.

This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

Effect of temperature on pupa development and sexual maturity of laboratory Anastrepha obliqua adults.

The effect of four temperatures (18, 20, 25 and 30°C) on pupa development and sexual maturity of Anastrepha obliqua adults was investigated under laboratory conditions. The results showed that the duration of the pupal stage decreased with an increase in temperature (29, 25, 13 and 12 days, respectively), and maintaining the pupae at 18°C and 20°C results in a low percentage of pupation, pupa weight loss and lesser flying ability. However, it significantly favored sexual behavior, a higher proportion of sexual calls and matings. While enhanced pupa development was observed at a temperature of 30°C, adults had low sexual efficiency, as well as a lower proportion of calls and matings. Gas chromatography-mass spectrometry (GC-MS) analysis of male volatiles showed that the amount of (Z,E)-α-farnesene did not vary among males from pupae reared at different temperatures; however, less (E,E)-α-farnesene was emitted by males obtain from pupa reared at 30°C. Male flies kept at 30°C during their larval stage had more (Z)-3-nonenol and, also, an unknown compound was detected. The fecundity of the females was higher at low temperatures. Regarding fertility, no significant differences were found between temperatures. The optimal temperature on pupa development was 25°C when males displayed ideal attributes for rearing purposes.

Beyond Protein Synthesis; The Multifaceted Roles of Tuberin in Cell Cycle Regulation.

The ability of cells to sense diverse environmental signals, including nutrient availability and conditions of stress, is critical for both prokaryotes and eukaryotes to mount an appropriate physiological response. While there is a great deal known about the different biochemical pathways that can detect and relay information from the environment, how these signals are integrated to control progression through the cell cycle is still an expanding area of research. Over the past three decades the proteins Tuberin, Hamartin and TBC1D7 have emerged as a large protein complex called the Tuberous Sclerosis Complex. This complex can integrate a wide variety of environmental signals to control a host of cell biology events including protein synthesis, cell cycle, protein transport, cell adhesion, autophagy, and cell growth. Worldwide efforts have revealed many molecular pathways which alter Tuberin post-translationally to convey messages to these important pathways, with most of the focus being on the regulation over protein synthesis. Herein we review the literature supporting that the Tuberous Sclerosis Complex plays a critical role in integrating environmental signals with the core cell cycle machinery.