Untreated Disease Research Articles

Drug repurposing for hard-to-treat human alveolar echinococcosis: pyronaridine and beyond.

Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.

Detection of chronic obstructive pulmonary disease and frequency of cardiopulmonary events in patients with a significant smoking history hospitalised for acute myocardial infarction

Abstract Background Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and also myocardial infarction (MI). Patients with COPD are more likely to have MI than those without and adequately treating COPD might improve cardiovascular outcomes. Reliable diagnosis is important for appropriate treatment. Prevalence of COPD in those hospitalised for MI has not been accurately established. Blood eosinophil count is an important guide to the benefit of inhaled corticosteroid (ICS) treatment in COPD. We aimed to accurately characterise lung function, symptom burden, eosinophil count and cardiopulmonary events in those with a significant smoking history hospitalised for acute MI. Methods Participants (n=216) with a smoking history of ≥10 pack-years currently hospitalised for acute MI were recruited at a single UK centre. Microspirometry and completion of the COPD Assessment Test (CAT) questionnaire were performed at enrolment. Presence and severity of COPD was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. A high burden of COPD symptoms was defined as a CAT score of >10. Repeat CAT and assessment for relevant cardiopulmonary events was undertaken at 3 months and 1 year after enrolment. Results In the enrolled cohort, median age was 60 years (IQR 53-67), 26% were female, 57% were current smokers and median pack-year history was 32 (23-45). 41 of 216 (19 %, [95% CI 14-25]) had evidence of COPD, defined as FEV1/FEV6 <0.7 on best-attempt microspirometry, with 39 (95%) being GOLD2 or greater. Of the 41 with detected COPD, only 15 (37%, [22-53]) had a prior diagnosis. In those with evidence of COPD, a high burden of COPD symptoms was present in 63% of participants at enrolment, 40% at 3 months and 45% at 1 year. 20% [9-35] were receiving inhaled corticosteroids at enrolment. 63% [47-78] had eosinophil count ≥100 cells/mm3 and 17% [7-32] ≥300 cells/mm3. Among those with detected COPD, after 1 year 19.5% (95% CI 9-35%) had suffered a respiratory illness requiring prescription of medication, which was numerically but not statistically significantly higher than those without detected COPD (14.3% [10-20%]). In the COPD cohort, death, infection requiring hospitalisation, MI or unplanned coronary revascularisation, and bleeding requiring hospitalisation each occurred on two occasions (4.9%). Conclusions Based on these data, the prevalence of microspirometry-diagnosed COPD of any severity in patients with significant smoking history hospitalised for MI is around 19%. There is a high rate of undiagnosed and untreated disease, a significant burden of symptoms, including during convalescence, and around a 20% incidence of respiratory illness requiring medical treatment at 1 year. Gathering accurate data from this group is helpful in planning research and service improvement. Increasing detection of COPD in patients with MI would lead to improved cardiopulmonary outcomes.

A sex-based analysis of complete blood count features during acute, untreated Lyme disease

IntroductionAlthough lymphopenia has been described in acute Lyme disease (LD), the complete blood count (CBC) has not been comprehensively examined, nor have sex-based analyses been conducted. We analyzed CBC values and identified sex-based trends among patients with early LD by comparing both to controls without a history of LD and to patients’ pre-morbid values.MethodsWe enrolled participants from the Mid-Atlantic US with diagnostic erythema migrans and controls with no history of LD. CBC results were obtained, and patient information was recorded using standardized instruments. We also calculated a neutrophil-to-lymphocyte ratio (NLR). We used linear regression to test that CBC results would differ (a) between antibiotic-naive patients with early LD and controls and (b) by measures of acute disease severity. We also performed stratified analyses to assess sex-based differences.ResultsIn total, 236 antibiotic-naive patients with early LD had significantly lower lymphocytes (β = −0.34, p < 0.001) and significantly higher monocytes (β = 0.09, p = 0.002) and NLRs (β = 0.99, p < 0.001) than 61 controls in adjusted analyses. Lymphocytes, monocytes, and NLRs also changed significantly from pre-morbid to acute LD (p < 0.001 for all). Only the NLR was consistently significantly associated with disease severity. A higher proportion of male patients with early LD had acute lymphopenia than female patients with early LD (31.93% vs. 19.66%, p = 0.03); this difference was not present among controls.ConclusionThe presence of lymphopenia and the absence of an elevated total white blood cell count make LD an important diagnostic consideration in patients presenting with undiagnosed infectious syndromes in endemic regions. This may be especially true for male patients.

A recent shift in the Puccinia striiformis f. sp. tritici population in Serbia coincides with changes in yield losses of commercial winter wheat varieties

Wheat yellow (stripe) rust, caused by the fungus Puccinia striiformis f.sp. tritici (Pst), is a devastating disease of wheat worldwide. The success of Pst is largely due to the pathogens ability to rapidly overcome host resistance, generating new races that are easily dispersed between territories through wind-borne transmission of Pst urediniospores. Thus, first signs of entry of new Pst races into a region is usually captured by changes in disease severity. To examine any alterations of winter wheat variety response to Pst infection in Serbia, we analyzed yield and Pst disease severity in field trials conducted in 2014, 2021, and 2023. We specifically focused on analyzing Pst disease severity at growth stages related to yield. Associations between qualitative variables (variety, year) and quantitative variables (yield in untreated plots, yield loss, and disease index (DI) of Pst infection) were analyzed using Principal Component Analysis with mixed data. A General Linear Model was used to investigate the most influential factors on yield, yield loss, and Pst infection. The results indicated that yellow rust disease severity increased over the past decade, suggesting a potential recent change in the Pst population in Serbia. Comparative population genetic analysis of Pst samples from the 2023 wheat season and those collected in Serbia in 2014 confirmed a potential change in the Pst population. In addition, we found that yield losses across wheat varieties varied independently of Pst infection levels, indicating that wheat varieties differ in their ability to overcome damage caused by high levels of Pst infection. Given that the level of pathogen pressure triggering susceptibility reactions is cultivar-specific, our study highlights the need for a deeper focus on the mechanisms underlying these differences. Expanding our understanding of the interactions between pathogens, plant defense responses, and the ability of cultivars to mitigate yield losses will better equip us to predict and prevent potential yield losses in commercial wheat varieties due to yellow rust in the future.

Cardiac Arrest During Exertion as a Presentation of Undiagnosed Kawasaki Disease: A Case Report

Background: Kawasaki Disease (KD) is self-limited vasculitis, the main consequence of which may be involvement of the coronary arteries, especially in patients without treatment. It is estimated that coronary artery aneurysms occur in 15% to 25% of untreated children. Patients with coronary aneurysms may remain asymptomatic for years. The first symptom may be life-threatening sudden cardiac arrest or myocardial ischaemia. Methods: We report a case of a 17-year-old boy with an insignificant past medical history who presented with sudden cardiac arrest. Results: During diagnostics, channelopathies, structural heart defects, drug abuse, and myocardial infarction were excluded. The patient underwent coronary angiography, confirmed by CT angiogram of the coronary vessels, which revealed most likely ruptured, clotted, well-calcified aneurysm of the left anterior descending artery (LAD) with collateral circulation, probably a consequence of untreated Kawasaki disease in early childhood. Conclusions: Complications of KD should be considered in the differential diagnosis of sudden cardiac arrest, especially in a young person.

Randomized controlled trial parallel-group on optimizing community pharmacist's care for the elderly: The influence of WhatsApp-Email delivered clinical case scenarios.

Drug-related problems (DRPs) significantly threaten the safety of the elderly. In order to improve pharmacists' ability to minimize these events, novel educational interventions that consider the current challenges in clinical practice are crucial. The primary objective is to assess the impact of two unique educational interventions on pharmacists' ability to identify DRPs. A total of 127 community pharmacies in the United Arab Emirates (UAE) were recruited and randomly allocated to one of three arms using a 1:1:1 allocation ratio. While a series of clinical case scenarios (N = 24) related to elderly care were established and validated and sent to pharmacists in Active Group A over a 3-month period, lengthy research articles focused on medication safety in elderly were emailed to pharmacists in Active Group B. The control group pharmacist received no intervention. Then, pharmacists self-reported the number, categories, and severity of DRPs and pharmacist recommendations. The incidence of DRPs identified by pharmacists was 10.8% in Active Group A, 2.0% in the Control Group (p = 0.011), and 3.8% in Active Group B (p = 0.014). A significant difference was observed in the proportion of DRP types between Active Group A and the Control Group. The most common DRPs in Active Group A were avoidable medication (14.7%) and untreated disease (9.2%). Pharmacists in Active Group A (37.2%) and Active Group B (32.3%) most commonly intervened by recommending the cessation of medication, while the most common intervention in the Control Group was recommending a decrease in dose (29.8%). The mean cost reduction per patient was highest in Active Group A (31.3 ±11.8 $), followed by Active Group B (20.8 ±8.6 $) and the Control Group (19.6 ±9.5 $). The mean time needed to resolve a DRP was shortest in Active Group A (7.3 ±3.5 minutes), followed by Active Group B (9.8 ±4.2 minutes) and the Control Group (9.8 ±5.7 minutes). Using WhatsApp to deliver clinical scenarios was effective in improving pharmacists' ability to identify and address DRPs in elderly patients, resulting in faster resolution and higher cost savings.

A Description of the Dental Health and Treatment of Ukraine Military at U.S. Army Clinics in Germany.

Since the start of the Russo-Ukrainian war, most reports have focused on trauma and combat conditions. Trauma care is essential; however, disease and nonbattle injuries (DNBIs) also burden armies and reduce combat effectiveness. Dental emergencies (DEs) account for a substantial portion of DNBI, but there is limited information on Ukrainian military dental readiness. In September 2023, investigators were informed that Ukrainian military personnel were treated for DEs at 2 dental clinics in Germany. The investigators requested deidentified data from the Corporate Dental System (CDS), which is a repository for dental treatment records utilized by the U.S. Army. The data request captured DE treatment performed for Ukrainian military personnel in Germany from January 1, 2023, to September 20, 2023. The CDS report on DE encounters included the following: Gender, age, procedure codes, and provider narratives. This study was approved by the U.S. Army Institute of Surgical Research Institutional Review Board as research not involving human subjects and provided Log Number H-24-030nh. The CDS report captured 408 Ukrainian military DE encounters. A total of 360 Ukrainian military personnel were treated for DE during the 9-month reporting period in 2023. Oral surgery was the most common DE treatment category and accounted for 55.8% (N = 201) of DE procedures. Restorative dentistry procedures accounted for 18.1% of DE procedures. Of the 27 multiple category treatments, 25 had oral surgery procedures as one of the treatments. Restorative dentistry procedures were performed in 19 of the multiple category cases. The DEs in the Ukrainian military cohort suggest that chronic, untreated dental disease has progressed without routine care for years. The assertion that caries has progressed to a nonrestorable condition is supported by the distribution that 63% of all DE visits included oral surgery treatment. Based on the distribution of dental treatment, US dental officers must be proficient in oral surgery and prosthodontic care.

Coeliac Disease in Children—A Clinical Review Including Novel Treatment Agents

Coeliac disease (CD) affects almost of 1% of the population, yet remains undiagnosed in the majority. Though the demonstration of enteropathy in duodenal biopsy was traditionally the essential criterion for the diagnosis of coeliac disease, the guidelines published by the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) in 2012, and revised in 2020, paved the way to a no-biopsy approach to diagnosis. In a select group of children meeting certain criteria, a definitive diagnosis of CD can now be made without the need for duodenal biopsies. This is being increasingly applied in clinical practice. It is well established that untreated coeliac disease is associated with several chronic adverse health conditions. At present, a strict gluten-free diet remains the only effective treatment for CD. The advances in our understanding of the pathogenesis of CD have led to a search for alternative treatment agents. Several investigational agents are in various phases of clinical trials at present. In this review, we outline the clinical aspects of coeliac disease and summarise various investigational treatment agents.

Scaffolds in periodontal regeneration- A brief review

The periodontium constitutes the supportive framework of a tooth, comprising the integration of the periodontal ligament, cementum, gingiva, and alveolar bone. The periodontium's health is compromised by the infiltration of bacteria due to local or systemic factors. Untreated periodontal disease can lead to the loss of attachment and eventual tooth loss, necessitating effective therapy. Tissue engineering is a multidisciplinary approach that combines engineering techniques with life sciences principles to generate biological substitutes for damaged tissues, aiming to restore, maintain, or enhance their function. In recent years, various scaffolding technologies have emerged, transitioning from monophasic to multi-phasic/bioactive scaffold systems, with the goal of three-dimensional regeneration of periodontal tissue rather than mere promotion of healing. This review discusses tissue engineering principles, materials, and recent advancements in scaffold design for periodontal tissue regeneration, along with their efficacy tested both in vitro and in vivo.

Concurrent acute cystitis, pancolitis, and tubo-ovarian abscess following laparoscopic ovarian cystectomy: a case report

BackgroundInadequate surgical interventions can lead to serious complications such as tubo-ovarian abscesses in the upper female genital system, often resulting from untreated pelvic inflammatory disease. Pelvic inflammatory disease, caused by infections like Chlamydia trachomatis and Neisseria gonorrhoeae, leads to scarring and adhesions in the reproductive organs, with common risk factors including intrauterine device use and multiple sexual partners. Pelvic inflammatory disease primarily affects sexually active young women and can manifest with varied symptoms, potentially leading to complications like ectopic pregnancy, infertility, and chronic pelvic pain if untreated.Case presentationThis case report presents a unique scenario involving a 17-year-old sexually inactive female who experienced concurrent tubo-ovarian abscess, acute cystitis, and pancolitis following laparoscopic ovarian cystectomy. Pelvic inflammatory disease and its complications are well-documented, but the simultaneous occurrence of acute cystitis and pancolitis in this context is unprecedented in the medical literature. The patient’s presentation, clinical course, and management are detailed, highlighting the importance of considering diverse and severe complications in individuals with a history of gynecological surgeries.ConclusionsOur case report highlights the need for healthcare professionals to remain vigilant for atypical presentations of gynecological complications and emphasizes the value of interdisciplinary collaboration for optimal patient care. We encourage further research and awareness to enhance understanding and recognition of complex clinical scenarios associated with gynecological procedures.

Oral Health Status and Oral Healthcare System in Indonesia: A Narrative Review

Abstract Aim: To assess the current situation regarding oral health status and system in Indonesia through the existing literature and government documents, identify challenges, and propose recommendations for the future. Materials and Methods: A literature search was conducted from June to October 2023 through the scientific databases of PubMed, Web of Science, and Google Scholar, including published articles from 2013 to 2023. The following main keywords were used: “Indonesia,” “oral health system,” “oral healthcare system,” “oral health policy,” “oral health promotion,” “oral health coverage,” and “oral health status.” Articles without any restrictions on study design, review articles, regional or national oral health reports, and Indonesian health laws or regulations were included. Data extracted from the included studies were synthesized and presented into several subgroups. Results: Despite the establishment of a health system in 1982, the oral health status of Indonesian people remains unsatisfying. The prevalence of untreated caries and periodontal disease is still high. Several policies and programs have been implemented to tackle those problems; however, Indonesia still has many challenges to overcome, including geographic constraints, uneven distribution of dental personnel, low public awareness and information on oral care utilization, insufficient resource allocation, and lack of prevention and promotion programs. Conclusion: The oral health status of the Indonesian population remains unsatisfactory. Future actions should emphasize on equal access and distribution of dental care, strengthen monitoring and evaluation of ongoing programs, integrate oral health into the national health agenda, and allocate adequate resources to support oral health initiatives.

Plea to radiologists: Please consider Mahvash disease when encountering an enlarged pancreas.

Radiologists play a key role in establishing an early and accurate diagnosis, especially for rare diseases. Mahvash disease (OMIM 619290) is an autosomal recessive hereditary disease caused by inactivating mutations of the glucagon receptor and its main clinical consequences are pancreatic neuroendocrine tumors and in some cases, porto-sinusoidal vascular disease and portal hypertension. Untreated Mahvash disease can be lethal. The diagnosis of Mahvash disease has almost always been delayed in the past due to radiologists' unawareness of or unfamiliarity with the unique imaging features of Mahvash disease which are moderately to enormously enlarge pancreas with preserved pancreas contour and parenchyma without vascular involvement or lymphadenopathy. These features help differentiate Mahvash disease from other etiologies of diffusely enlarged pancreas such as diffuse pancreatic ductal carcinoma, diffuse pancreatic lymphoma, and autoimmune pancreatitis. Invoking Mahvash disease in the differential diagnosis of an enlarged pancreas has recently been shown to facilitate early diagnosis. To prevent missing the diagnosis of this significant disease, I sincerely ask radiologists to consider Mahvash disease in their differential diagnoses of diffusely enlarged pancreas.

Takayasu arteritis in an adolescent with untreated Crohn's disease: A case report

AbstractExtraintestinal manifestations in inflammatory bowel disease (IBD) most frequently involve the joints, skin, and organs such as the liver and pancreas. Inflammation of the aorta is less commonly described in pediatrics, although it has been described in adults. We report a case of an adolescent female with Crohn's disease who presented with worsening diarrhea, vomiting, and weight loss, found to have aortitis on imaging. We review the pathogenesis and clinical features of Takayasu arteritis, as well as some of its similarities to IBD to raise awareness, as early detection of this less‐known extraintestinal manifestation has been associated with better outcomes.

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis

BackgroundJuvenile dermatomyositis (JDM) is a systemic vasculopathy associated with metabolic derangements and possible increased risk for premature atherosclerosis. Oxidation of low-density lipoprotein (LDL) in the endothelium is an early step in atherosclerotic plaque formation. It is not known if oxidized LDL is altered in children with untreated JDM. The deposition of oxidized LDL in the vasculature of muscle biopsies (MBx) from patients with untreated JDM and pediatric controls was assessed.FindingsFrozen tissue sections of MRI-directed MBx from 20 female children with untreated JDM and 5 female controls were stained with DAPI and fluorescently labeled antibodies against von Willebrand factor (vWF) and LDL oxidized by copper (oxLDL). Blood vessels were identified by positive vWF staining, and total fluorescence of oxLDL within the vessel walls was measured. Children with untreated JDM had increased deposition of oxLDL in the walls of muscle vasculature compared to healthy children (difference in means ± SEM = 19.86 ± 8.195, p = 0.03). Within the JDM cohort, there was a trend towards increased oxLDL deposition with longer duration of untreated disease (r = 0.43, p = 0.06). There was no significant correlation found between oxLDL deposition and markers of acute JDM disease activity including disease activity scores or muscle enzymes.ConclusionsThis study found increased deposition of oxLDL within blood vessels of children with untreated JDM supporting the concern that these children are at increased risk for premature atherosclerosis from chronic exposure to vascular oxLDL. This study highlights the importance of early diagnosis and treatment initiation to ameliorate cardiovascular damage.

Gastrointestinal and Hepatobiliary Manifestations Associated with Untreated Celiac Disease in Adults and Children: A Narrative Overview.

Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described.

Ear disease, hearing loss, and cognitive outcomes in high school children who were previous participants in a randomized placebo controlled trial of an 11 valent conjugate pneumococcal vaccine administered in infancy

The WHO estimates that close to 1.7 billion people worldwide have hearing loss; 34 million of whom are children, with 90% residing in low- and middle-income countries. While the effects of ear disease and hearing loss on language, academic, and behavioral development are established, there is remarkably little data on intellectual and other cognitive differences. Here we report results from an extension of a randomized controlled vaccination trial originally carried out between 2000 and 2004. Primary caregivers completed demographic and household questionnaires. Beginning in 2016, children were followed up for a hearing and ear disease evaluation. Participants also completed extensive cognitive testing, which included the domains of IQ, language, attention and processing speed, visual and visuospatial skills, and learning and memory. The association between ear disease and hearing loss and each of the cognitive outcomes was examined using multivariate linear regression models. We followed up 8926 children ages 14-19 years old. Children with hearing loss or ear disease had lower socioeconomic status compared to children without. However, even after controlling for a high number of covariates, all levels of ear disease or hearing loss were associated with clinically relevant reductions across all cognitive domains, though effect sizes were small. Even mild ear disease or hearing loss was associated with a-0.15 (95% CI:-0.20,-0.11) and a-0.23 (95% CI:-0.32,-0.14) standard deviation reduction, respectively, in IQ. The effects of ear disease and hearing loss were additive as children with both had the lowest cognitive scores. Untreated ear disease and hearing loss exert measurable effects on cognition that are able to be detected into the teenage years. Early identification of hearing loss and chronic ear disease may have lifelong benefits. Individuals with ear disease and/or hearing loss may require supports and services in addition to those related to speech and language therapy. The Bill and Melinda Gates Foundation OPP1142570.

Colombia's Armed Conflict and Dental Caries among Adults.

This study aimed to determine the association between residing in municipalities with armed conflict and dental caries among adults in Colombia. Data from 9,194 individuals aged 18-79 years, who participated in the Fourth National Oral Health Survey in 2014, were linked with information on the presence and intensity of the armed conflict experienced in their municipality of residence between 2000 and 2012 (extracted from the Resource Centre for Conflicts Analysis). Dental caries was determined through clinical examinations and summarised using the numbers of decayed teeth (DT), decayed and filled teeth (DFT), and decayed, missing, and filled teeth (DMFT). Two-level negative binomial regression models were fitted, with adults nested within municipalities, to test the association between armed conflict indicators and caries outcomes after adjustment for covariates. The mean DT, DFT, and DMFT scores were 1.75 (SD = 2.36), 6.03 (SD = 4.53), and 10.27 (SD = 7.11), respectively. Of the 197 municipalities included in the analysis, 12.2% experienced conflict permanently and 18.3% experienced high-intensity conflict. In crude analysis, adults living in municipalities with more presence and intensity of armed conflict had lower DT and DMFT, but not DFT scores. After adjustment for covariates, only the (high) intensity of conflict was associated with lower DT (rate ratio: 0.64; 95% confidence interval [CI]: 0.47-0.87), DFT (RR: 0.82; 95% CI: 0.71-0.95), and DMFT scores (RR: 0.81; 95% CI: 0.74-0.89). This study found that Colombian adults residing in municipalities with high intensity of conflict had lower levels of untreated disease and caries experience.

Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. Tomivosertib treatment also decreased action potential amplitude and produced alterations in the magnitude of after hyperpolarizing currents, suggesting modification of Na+ and K+ channel activity as a consequence of drug treatment. Parallel to the effects on electrophysiology, eFT508 treatment led to a profound loss of eIF4E serine 209 phosphorylation in primary sensory neurons, a specific substrate of MNK, within 2 min of drug treatment. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.

Innovative Approaches to Clinical Diagnosis: Transfer Learning in Facial Image Classification for Celiac Disease Identification

Background: Celiac disease arises from gluten consumption and shares symptoms with other conditions, leading to delayed diagnoses. Untreated celiac disease heightens the risk of autoimmune disorders, neurological issues, and certain cancers like lymphoma while also impacting skin health due to intestinal disruptions. This study uses facial photos to distinguish individuals with celiac disease from those without. Surprisingly, there is a lack of research involving transfer learning for this purpose despite its benefits such as faster training, enhanced performance, and reduced overfitting. While numerous studies exist on endoscopic intestinal photo classification and a few have explored the link between facial morphology measurements and celiac disease, none have concentrated on diagnosing celiac disease through facial photo classification. Methods: This study sought to apply transfer learning techniques with VGG16 to address a gap in research by identifying distinct facial features that differentiate patients with celiac disease from healthy individuals. A dataset containing a total of 200 facial images of adult individuals with and without celiac condition was utilized. Half of the dataset had a ratio of 70% females to 30% males with celiac condition, and the rest had a ratio of 60% females to 40% males without celiac condition. Among those with celiac condition, 28 were newly diagnosed and 72 had been previously diagnosed, with 25 not adhering to a gluten-free diet and 47 partially adhering to such a diet. Results: Utilizing transfer learning, the model achieved a 73% accuracy in classifying the facial images of the patients during testing, with corresponding precision, recall, and F1 score values of 0.54, 0.56, and 0.52, respectively. The training process involved 50,178 parameters, showcasing the model’s efficacy in diagnostic image analysis. Conclusions: The model correctly classified approximately three-quarters of the test images. While this is a reasonable level of accuracy, it also suggests that there is room for improvement as the dataset contains images that are inherently difficult to classify even for humans. Increasing the proportion of newly diagnosed patients in the dataset and expanding the dataset size could notably improve the model’s efficacy. Despite being the first study in this field, further refinement holds promise for the development of a diagnostic tool for celiac disease using transfer learning in medical image analysis, addressing the lack of prior studies in this area.

Pro-inflammatory cytokines and antioxidative enzymes as salivary biomarkers of dentofacial infections in children.

Dentofacial infection resulting from untreated dental caries or periodontal disease is a serious disease that can spread to deeper tissues of the face and neck. The present study aimed to analyze the salivary cytokine profile and oxidative stress parameters as potential biomarkers of acute odontogenic infections in children. The prospective study group (DI) consisted of 28 children aged 3-17 years with acute dentofacial infections, and the control group (CG) comprised 52 children aged 4-17 years with uncomplicated dental caries. The cytokine profile was analyzed using the Bio-Plex Pro™ Human Cytokine 27-plex kit. In addition, oxidative stress parameters, such as catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), manganese SOD (Mn-SOD), copper-zinc SOD (CuZn-SOD), total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA), in the saliva of children in both groups were compared. The levels of interleukin 6 (IL-6), macrophage inflammatory protein 1 alpha (MIP-1α) and tumor necrosis factor alpha (TNF-α) were significantly increased in children with dentofacial infections as compared to CG. In contrast, the levels of other pro-inflammatory cytokines, such as IL-1β, IL-1 receptor agonist (IL-Ra), IL-8, monocyte chemoattractant protein 1 (MCP-1), and MIP-1β, did not show statistically significant differences between the 2 groups. Among the measured oxidative stress and antioxidative parameters, only CAT and GR were elevated in children with dentofacial infections as compared to controls. IL-6, MIP-1α, TNF-α, CAT, and GR can serve as selective biomarkers of oral cavity inflammation in children. These biomarkers can be useful in identifying and monitoring the progress and treatment of bacterial infections resulting in dentofacial inflammation.