An analysis of contributing factors of head and neck space infections of odontogenic origin: A long-term retrospective clinical study (including COVID-19 pandemic period).

BACKGROUND: The purpose of this study is to investigate predisposing factors for the head and neck infections (HNIs), regarding to the demographic data, anatomical spaces, microbiology and antibiotic sensitivity for affected patients. MATERIAL AND METHODS: A 13-year of retrospective study evaluating 470 patients with HNIs, treated as inpatient management in the Department of Oral and Maxillofacial Surgery of KyungHee University school of Dentistry, Seoul, Korea, from January 2009 to February 2022. Statistical analysis of demographic, time-related, anatomic, microbiologic, and treatment variables were investigated for each patient. RESULTS: The frequency of HNIs was significantly higher in 50's in males, followed by 70's in females. High Severity score (SS) were significantly associated with increased LOH (Length of hospital stay) and LOM (Length of medication), while LOH showed more intensive relationship compared with LOM. The most frequently involved space in abscess was submandibular space, though incidence and severity of HNIs shows declining tendency throughout 13-year research. Streptococcus viridans was the most predominant species isolated from pus culture growth, and a combination of ampicillin and sulbactam was the 1st choice of antibiotics intravenously. According to the comparison analysis between recommended antibiotics from resistance testing result and clinically administered antibiotics, final coincidence rate was estimated about 55%. CONCLUSIONS: Due to HNIs being multifactorial, predicting progression and management of HNIs is still a challenge for oral and maxillofacial surgeons. The present study showed several predisposing factors of SHNIs and their correlations, which could contribute to earlier diagnosis and more effective treatment planning for clinicians, thereby leading to the improvement of prognosis for patients, ultimately.

First Direct Measurement Constraining the

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.

First Observation of the ß3αp Decay of

The ß-delayed proton decay of ^{13}O has previously been studied, but the direct observation of ß-delayed 3αp decay has not been reported. Rare 3αp events from the decay of excited states in ^{13}N^{⋆} provide a sensitive probe of cluster configurations in ^{13}N. To measure the low-energy products following ß-delayed 3αp decay, the Texas Active Target (TexAT) time projection chamber was employed using the one-at-a-time ß-delayed charged-particle spectroscopy technique at the Cyclotron Institute, Texas A&M University. A total of 1.9×10^{5} ^{13}O implantations were made inside the TexAT time projection chamber. A total of 149 3αp events were observed, yielding a ß-delayed 3αp branching ratio of 0.078(6)%. Four previously unknown α-decaying excited states were observed in ^{13}N at 11.3, 12.4, 13.1, and 13.7 MeV decaying via the 3α+p channel.

Finger injuries by eyebrow razor blades in infants.

Infants are occasionally injured while playing with their mother's eyebrow razor, and we have treated several infants with flexor tendon injuries, which in some cases were accompanied by damage to the corresponding digital nerves and/or vessels. Here, we report the outcomes in a retrospective case series, with a review of literature. Between January 2013 and October 2019, 8 patients who met our inclusion criteria were initially investigated. The inclusion criteria were: (1) injured by an eyebrow razor during fiddling or grasping, and (2) the availability of complete medical records and radiological data, with follow-up of at least 2 years. The core sutures were performed using a modified Becker (4-strand) method for flexor digitorum profundus (FDP). Nerves and/or vessels were repaired under microscopy. A long-arm mitten cast was then applied, with the fingers slightly flexed in a resting position, for 3 weeks. Then, the children were allowed to return to unrestricted activity. Formal outpatient hand therapy was not performed. Mean postnatal age was 6.3 months. The FDP was injured in zones 1 and 2 in 3 and 5 infants, respectively. Most of the infants were injured near a dressing table, in the bedroom used by their mother. The colors of these razors were all bright, except for one achromatic (white) razor. All of the razors had been left uncovered, without their cap, or were left open in the case of hinged razors. At a mean follow-up of 35.8 months, range of motion was evaluated by the Strickland and modified Strickland methods; all results were "excellent". We encountered no significant complications in any digit: neuroma, tendon retear, stiffness or necrosis. Uncapped or unfolded colorful eyebrow razors pose a high risk of tendon section with concurrent neurovascular injury in infants. Although satisfactory outcomes can be expected, it seems important to prevent the injury through fastidious parental care and changing razor design and color. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Evaluation of functional recovery in the intrinsic and flexor muscles after nerve transfer for ulnar nerve lesion. A new measurement method: The Cha method.

"Supercharge" end-to-side (SETS) nerve transfer for lesions of the proximal ulnar nerve is a recognized novel option, but improvement in motor function after surgery has not been properly evaluated. We therefore propose a modified method for quantitative evaluation of improvement in the intrinsic hand strength. We screened 216 patients with proximal ulnar nerve lesions who presented to our outpatient department from 2012 to 2020. Of these, 101 met our inclusion/exclusion criteria and were evaluated just before surgery. We used a novel method to measure finger abduction ("2nd-abd"), adduction ("5th-add"), and ring and little finger flexion strength ("4,5 grip"), and analyzed correlations with established pinch strength data. The male:female sex ratio was 86:15, and the ratio dominant to nondominant arm involvement was 68:33. All strength measurements were analyzed as percentage affected to contralateral normal side. On Pearson correlation analysis, the strength ratios for "4,5 grip", "2nd-abd", and "5th-add", but not "5 fingers (total) grip", showed significant positive correlation with key and oppositional pinch strength (all p < 0.001). Additionally, linear regression analysis showed identical results for each strength correlation with key/oppositional pinch, except for "5 fingers total) grip" (all, p < 0.001). SETS is a reasonable alternative for lesions of the proximal ulnar nerve. The measurement method we propose is feasible for specific assessment of intrinsic muscle strength, which improves after surgery. LEVEL OF EVIDENCE: Diagnostic, level IV.

Primary repair of extensor pollicis longus rupture after volar locking plating for distal radial fracture.

We presumed that primary repair would be possible if the extensor pollicis longus (EPL) rupture after volar locking plating (VLP) for distal radius fracture (DRF) was diagnosed earlier. Thus, five cases of EPL ruptures were resolved via primary repair rather than extensor indicis proprius (EIP) transfer, so we reported the clinical outcomes of at least 2 years follow-up since EPL repair. Of 588 consecutive patients with the fractures treated between January 2016 and December 2019, 501 who met out inclusion/exclusion criteria were initially investigated. We informed patients of: (1) the ordinary range of motion of thumb at full wrist flexion/extension; (2) the proper tone of thumb extension compared to the contralateral thumb; and (3) the degree of pain/discomfort during thumb exercise. After discharge, we called each patient monthly commencing at 8 weeks postoperatively to enquire if any of those had worsened, by telephone. Five patients had ruptured EPLs diagnosed at a mean of postoperative-12.8 weeks. Three came to outpatient department for suspected tendon rupture just after telephone survey with the authors. The other two visited after detecting insufficiency in the three items, during the period between telephone inquiries. In four, the torn EPL were encapsulated by tendon sheathes. Extension lag at interphalangeal joint was absent and other clinical outcomes associated with DRF were all satisfactory at final follow-up. Primary repair of EPL rupture (rather than EIP transfer) is possible if patients are properly followed up after VLP for DRF. LEVEL OF EVIDENCE: Level IV, retrospective case series.

ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium.

BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.

Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

Effect of dipeptidyl peptidase IV inhibitors, thiazolidinedione, and sulfonylurea on osteoporosis in patients with type 2 diabetes: population-based cohort study.

The population-based cohort study used the Korean National Health Insurance claims database to evaluate the effect of anti-diabetic drugs on osteoporosis. The use of DPP-IV inhibitors does not increase the risk of osteoporosis compared with the use of sulfonylureas in patients with type 2 diabetes mellitus, while a weak association was found between thiazolidinediones and increased risk of osteoporosis. PURPOSE: The current study aimed to evaluate the effect of dipeptidyl peptidase IV inhibitors (DPP-IVi), thiazolidinedione (TZD), and sulfonylurea (SU) on osteoporosis in patients with type 2 diabetes. METHODS: A population-based cohort study was conducted in the Republic of Korea using the Korean National Health Insurance claims database. Data from 2012 to 2017 for patients of 50-99 years of age who were prescribed DPP-IVi, TZD, or SU during 2013-2015 were extracted from the database. Based on pre-defined criteria, a total of 381,404 patients were analyzed after inverse probability of treatment weighting. The association between the study drugs and osteoporosis was estimated using Cox proportional hazards models. Data of 220,166 patients who were prescribed DPP-IVi, 18,630 who were prescribed TZD, and 142,608 patients who were prescribed SU were set. RESULTS: In the multivariate-adjusted analysis, the hazard ratio (HR) of osteoporosis in the DPP-IVi group was not significantly different from that of the SU group (HR: 0.97; 95% confidence interval (CI) 0.94-1.00), whereas the HR of osteoporosis in the TZD group was higher (HR: 1.13; 95% CI 1.06-1.20). In the subgroup analysis, the HRs of osteoporosis were higher with pioglitazone (HR: 1.14; 95% CI 1.06-1.23) in the TZD group and with glibenclamides (HR: 1.39; 95% CI 1.09-1.77) in the SU group, whereas drugs with lower HR in the DPP-IVi group were saxagliptin (HR: 0.93; 95% CI 0.87-0.99) and sitagliptin (HR: 0.93; 95% CI 0.89-0.97). CONCLUSION: DPP-IV inhibitors do not increase the risk of osteoporosis compared with sulfonylureas in patients with type 2 diabetes mellitus, while a weak association was found between thiazolidinediones and increased risk of osteoporosis.

Acute Seymour fractures in children/adolescents overlooked as a simple nail injury: Reduction without pinning.

We retrospectively report the outcomes of several cases in which acute Seymour fractures were treated by open reduction of displaced distal bony fragments with concurrent nail repair, following complete incision and drainage without K-wire fixation. Among 21 patients surgically treated between March 2004 and December 2018, the final 12 were evaluated after at least 2 years of follow-up. All children/adolescents presented more than 24 h after the injury. All injuries were unreduced in the emergency department, with typical features of skin disruption around the eponychium/perionychium. Reduction was maintained without a K-wire after repairing the bone-periosteum-nail bed-nail plate of the distal fragment and the corresponding physis-periosteum-germinal matrix-proximal nail-fold of the proximal stump. Dorsal angulation, finger length, postoperative pain on visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, and active range of motion (ROM) were evaluated at the final follow-up. The mean patient age was 9.3 years (range, 3-13 years) and the mean time from injury to surgery was 35 h (range, 28-44 h). Only one child suffered a superficial infection; however, it resolved with 1 week of oral antibiotic treatment. At the final follow-up, mean dorsal angulation was 0.50° ± 1.24°; the length ratio compared with the corresponding contralateral phalanx was 98% (both, P > 0.05). The final pain on VAS, DASH score, and ROM ratio were 0.25 ± 0.45, 0.83 ± 1.34, and 99 ± 2%, respectively. Unreduced Seymour fractures presenting more than 24 h after the injury were treated by proper debridement and reduction of the fracture without the use of a K-wire. However, to determine whether the infection rate is definitively lower, this procedure should be compared with the conventional procedure using a K-wire. Level of Evidence: Therapeutic level IV.

MRI Features May Predict Molecular Features of Glioblastoma in Isocitrate Dehydrogenase Wild-Type Lower-Grade Gliomas.

BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma. MATERIALS AND METHODS: In this multi-institutional retrospective study, pathologically confirmed IDH wild-type lower-grade gliomas from 2 tertiary institutions and The Cancer Genome Atlas constituted the training set (institution 1 and The Cancer Genome Atlas, 64 patients) and the independent test set (institution 2, 57 patients). Preoperative MRIs were analyzed using the Visually AcceSAble Rembrandt Images and radiomics. The molecular glioblastoma status was determined on the basis of the presence of EGFR amplification and TERT promoter mutation. Molecular glioblastoma was present in 73.4% and 56.1% in the training and test sets, respectively. Models using clinical, Visually AcceSAble Rembrandt Images, and radiomic features were built to predict the molecular glioblastoma status in the training set; then they were validated in the test set. RESULTS: In the test set, a model using both Visually AcceSAble Rembrandt Images and radiomic features showed superior predictive performance (area under the curve = 0.854) than that with only clinical features or Visually AcceSAble Rembrandt Images (areas under the curve = 0.514 and 0.648, respectively; P < . 001, both). When both Visually AcceSAble Rembrandt Images and radiomics were added to clinical features, the predictive performance significantly increased (areas under the curve = 0.514 versus 0.863, P < .001). CONCLUSIONS: MR imaging features integrated with machine learning classifiers may predict a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

Involvement of the Olfactory Apparatus by Gliomas.

The olfactory bulbs and tracts are central nervous system white matter tracts maintained by central neuroglia. Although rare, gliomas can originate from and progress to involve the olfactory apparatus. Through a Health Insurance Portability and Accountability Act-compliant retrospective review of the institutional teaching files and brain MR imaging reports spanning 10 years, we identified 12 cases of gliomas involving the olfactory bulbs and tracts, including 6 cases of glioblastoma, 2 cases of anaplastic oligodendroglioma, and 1 case each of pilocytic astrocytoma, diffuse (grade II) astrocytoma, anaplastic astrocytoma (grade III), and diffuse midline glioma. All except the pilocytic astrocytoma occurred in patients with known primary glial tumors elsewhere. Imaging findings of olfactory tumor involvement ranged from well-demarcated enhancing masses to ill-defined enhancing infiltrative lesions to nonenhancing masslike FLAIR signal abnormality within the olfactory tracts. Familiarity with the imaging findings of glioma involvement of the olfactory nerves is important for timely diagnosis and treatment of recurrent gliomas and to distinguish them from other disease processes.

Identifying different types of microorganisms with terahertz spectroscopy.

Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes. Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range. We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory. The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11. The yeasts exhibited particularly high dielectric constants reaching 5.63-5.97, which were even higher than that of water. These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials. In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment. By contrast, the deposition of the yeasts induced a red shift because their dielectric constant was higher than that of water. Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and ß-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.

Persistent Palatal Ulcerations. A Potential Manifestation of Juvenile Systemic Lupus Erythematosus.

Oral ulcerations in children and adolescents is a common occurrence and affects about 20-30% of this population. This case report describes a unique and serious autoimmune condition that presented with distinct oral findings that significantly supported the differential diagnosis of Juvenile Systemic Lupus Erythematosus in a 15 year-old female. Pediatric and general dentists should familiarize themselves with the condition to facilitate diagnosis with collaborative efforts with the medical team.

Parkin expression reverses mitochondrial dysfunction in fused in sarcoma-induced amyotrophic lateral sclerosis.

Fused in sarcoma (FUS) is a DNA/RNA-binding protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. The exact molecular mechanisms by which FUS results in neurotoxicity have not yet been fully elucidated. Here, we found that parkin is a genetic suppressor of defective phenotypes induced by exogenous human wild type FUS in Drosophila. Although parkin overexpression did not modulate the FUS protein expression level, the locomotive defects in FUS-expressing larvae and adult flies were rescued by parkin expression. We found that FUS expression in muscle tissues resulted in a reduction of the levels and assembly of mitochondrial complex I and III subunits, as well as decreased ATP. Remarkably, expression of parkin suppressed these mitochondrial dysfunctions. Our results indicate parkin as a neuroprotective regulator of FUS-induced proteinopathy by recovering the protein levels of mitochondrial complexes I and III. Our findings on parkin-mediated neuroprotection may expand our understanding of FUS-induced ALS pathogenesis.

Diffusion Characteristics of Pediatric Diffuse Midline Gliomas with Histone H3-K27M Mutation Using Apparent Diffusion Coefficient Histogram Analysis.

BACKGROUND AND PURPOSE: Diffuse midline gliomas with histone H3 K27M mutation are biologically aggressive tumors with poor prognosis defined as a new diagnostic entity in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. There are no qualitative imaging differences (enhancement, border, or central necrosis) between histone H3 wildtype and H3 K27M-mutant diffuse midline gliomas. Herein, we evaluated the utility of diffusion-weighted imaging to distinguish H3 K27M-mutant from histone H3 wildtype diffuse midline gliomas. MATERIALS AND METHODS: We identified 31 pediatric patients (younger than 21 years of age) with diffuse gliomas centered in midline structures that had undergone assessment for histone H3 K27M mutation. We measured ADC within these tumors using a voxel-based 3D whole-tumor measurement method. RESULTS: Our cohort included 18 infratentorial and 13 supratentorial diffuse gliomas centered in midline structures. Twenty-three (74%) tumors carried H3-K27M mutations. There was no difference in ADC histogram parameters (mean, median, minimum, maximum, percentiles) between mutant and wild-type tumors. Subgroup analysis based on tumor location also did not identify a difference in histogram descriptive statistics. Patients who survived <1 year after diagnosis had lower median ADC (1.10 × 10-3mm2/s; 95% CI, 0.90-1.30) compared with patients who survived >1 year (1.46 × 10-3mm2/s; 95% CI, 1.19-1.67; P < .06). Average ADC values for diffuse midline gliomas were 1.28 × 10-3mm2/s (95% CI, 1.21-1.34) and 0.86 × 10-3mm2/s (95% CI, 0.69-1.01) for hemispheric glioblastomas with P < .05. CONCLUSIONS: Although no statistically significant difference in diffusion characteristics was found between H3-K27M mutant and H3 wildtype diffuse midline gliomas, lower diffusivity corresponds to a lower survival rate at 1 year after diagnosis. These findings can have an impact on the anticipated clinical course for this patient population and offer providers and families guidance on clinical outcomes.

Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Association between BMI and risk of severe hypoglycaemia in type 2 diabetes.

AIM: This study aimed to assess the association between body mass index (BMI) and the development of severe hypoglycaemia in patients with type 2 diabetes (T2D), using nationwide data for the entire South Korean population. METHODS: The association between BMI and severe hypoglycaemia was retrospectively examined from claims and National Health examination data registered between 2002 and 2015. A total of 1,366,692 subjects assigned clinical codes for T2D and prescribed antihypoglycaemic agents were included. The primary outcome was an episode of severe hypoglycaemia after the baseline health examination. RESULTS: A total of 37,682 subjects (2.7%) experienced a new severe hypoglycaemic event during the follow-up period (mean: 8.6 years). An inverse J-shaped association was observed between BMI and severe hypoglycaemic events. The association between low BMI and high risk of severe hypoglycaemia was similar in subjects who had never smoked, did not consume alcohol, did not use insulin and had no major comorbidities, after adjusting for multiple confounding variables. This association was also found to be intensified in men, young people aged 30-49 years, those with major comorbidities and insulin users. CONCLUSION: BMI and severe hypoglycaemia were found to be inversely associated. Thus, those who fall into the category of having low BMI and high risk of severe hypoglycaemia should be warned about the risk of having a hypoglycaemic event and be properly informed about hypoglycaemia to minimize the risk of fatal hypoglycaemia-related outcomes.

A framework for automated conflict detection and resolution in medical guidelines.

Common chronic conditions are routinely treated following standardised procedures known as clinical guidelines. For patients suffering from two or more chronic conditions, known as multimorbidity, several guidelines have to be applied simultaneously, which may lead to severe adverse effects when the combined recommendations and prescribed medications are inconsistent or incomplete. This paper presents an automated formal framework to detect, highlight and resolve conflicts in the treatments used for patients with multimorbidities focusing on medications. The presented extended framework has a front-end which takes guidelines captured in a standard modelling language and returns the visualisation of the detected conflicts as well as suggested alternative treatments. Internally, the guidelines are transformed into formal models capturing the possible unfoldings of the guidelines. The back-end takes the formal models associated with multiple guidelines and checks their correctness with a theorem prover, and inherent inconsistencies with a constraint solver. Key to our approach is the use of an optimising constraint solver which enables us to search for the best solution that resolves/minimises conflicts according to medication efficacy and the degree of severity in case of harmful combinations, also taking into account their temporal overlapping. The approach is illustrated throughout with a real medical example.

Glutathione transferase modulates acute ethanol-induced sedation in Drosophila neurones.

Heavy alcohol consumption leads to neuropathological damage and alcohol use disorder, which affects the health of people and results in a cost burden. However, the genes modulating sensitivity to ethanol remain largely unknown. Here, we identified a novel gene, Drosophila glutathione transferase omega 1 (GstO1), which plays a critical role in regulating sensitivity to ethanol sedation. GstO1 mutant flies showed highly increased ethanol sensitivity. Furthermore, the expression level of GstO1 regulates the behavioural response to ethanol, because decreasing and increasing GstO1 affects sedation sensitivity in a contrasting manner. In addition, the RNA interference-mediated knockdown of GstO1 expression reveals that GstO1 mediates sensitivity to ethanol sedation in neurones, including dopaminergic and serotonergic neurones. Altogether, our findings provide the first evidence for the involvement of glutathione transferase in the response to alcohol in Drosophila and provide a novel mechanistic insight into the toxicity and sensitivity of ethanol exposure.