Significant Disease Research Articles

Excess cement and peri-implant disease: A cross-sectional clinical endoscopic study.

Crown cementation is a common technique for implant-supported prosthodontics. However, for possible slipping of the cement below the mucosal margin, its thorough removal poses some issues. The objective of this study was to evaluate the presence of submucosal cement residues in patients with peri-implant disease by endoscopic visualization and to investigate the potential correlation between the pathological scenario and the spatial position of cement residues. The study sample comprised 46 consecutive patients exhibiting clinical and radiographic signs of peri-implant disease around cement-retained crowns. When at first visit bleeding on probing was the only pathological sign, the area was debrided and then treated with antiseptic agents for 30 days. Only those patients for whom bleeding was still found at re-evaluation were included in the study. All implants were therefore endoscopically evaluated to identify possible submucosal cement residues. For all implants showing residual cement, the spatial position of the residual cement was recorded with respect to predefined points. Cement residues were detected in 80.4% of the patients and were predominantly located in the vestibular and lingual areas (88%). Analysis of the distances between the apical portion of the residues and anatomical landmarks revealed significant differences between mucositis and peri-implantitis patients (p=0.001). In cases of peri-implantitis, the cement residue was more apically located than in mucositis. The presence of cement residue was associated with peri-implant disorders in the majority of patients. A potential correlation between the position of residues and the peri-implant disease scenario is here suggested. A common method for fixing the crown on the dental implant is the use of specific cements. However, these products can slip below the gum line resulting in difficulties in their removal, which could cause peri-implant disease. This study aimed to evaluate the presence and location of residual cement hidden under the gums in patients with peri-implant disease, characterized by symptoms such as bleeding gums and, in some cases, bone loss around the dental implant. Using a small fiber-optic camera (endoscope), 46 patients were examined for any cement residue under the gums. The study showed that more than 80% of patients had cement residues, especially in the areas facing the cheeks and tongue. It was also found that in patients with a more severe form of inflammation (peri-implantitis), the cement was placed deeper than in those with a milder form (mucositis). This confirms that residual cement is common in patients with peri-implant disease, but also suggests that its location could influence the severity of the pathological manifestation. This finding highlights the importance of carefully removing all cement to prevent such complications.

Mutations in chikungunya virus nsP4 decrease viral fitness and sensitivity to the broad-spectrum antiviral 4′-Fluorouridine

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that has re-emerged to cause large outbreaks of human infections worldwide. There are currently no approved antivirals for treatment of CHIKV infection. Recently, we reported that the ribonucleoside analog 4′-fluorouridine (4′-FlU) is a highly potent inhibitor of CHIKV replication, and targets the viral nsP4 RNA dependent RNA polymerase. In mouse models, oral therapy with 4′-FlU diminished viral tissue burdens and virus-induced disease signs. To provide critical evidence for the potential of 4′-FlU as a CHIKV antiviral, here we selected for CHIKV variants with decreased 4′-FlU sensitivity, identifying two pairs of mutations in nsP2 and nsP4. The nsP4 mutations Q192L and C483Y were predominantly responsible for reduced sensitivity. These variants were still inhibited by higher concentrations of 4′-FlU, and the mutations did not change nsP4 fidelity or provide a virus fitness advantage in vitro or in vivo. Pathogenesis studies in mice showed that the nsP4-C483Y variant caused similar disease and viral tissue burden as WT CHIKV, while the nsP4-Q192L variant was strongly attenuated. Together these results support the potential of 4′-FlU to be an important antiviral against CHIKV.

Behavioral Signature of Equine Gastric Discomfort? Preliminary Retrospective Clinical Observations.

Gastric ulcer disease and other potentially painful gastric conditions are among the most common afflictions adversely affecting the welfare of domestic equids. A large percentage of affected animals may not display the classic signs of gastric disease, such as unexplained weight loss, poor hair coat, and inappetence until the disease becomes severe. As a clinical service within our equine referral hospital, we routinely evaluate 24-h video recorded samples of horses to assist clinicians in identifying subtle discomfort and potential sources or to scan for infrequent neurologic or cardiac-related behavioral events. Empirically, we have recognized discomfort behaviors that appear to be uniquely associated with gastric disease. These include frequent attention to the cranial abdomen (nuzzling, swatting, nipping, and/or caudal gaze focused on the abdomen caudal to the elbow) and/or deep abdominal stretching, often within the context of eating, drinking, and/or anticipating feeding. To systematically evaluate the reliability of these purported gastric discomfort behaviors, we reviewed 30 recent 24-h video behavior evaluation cases for which (1) the clinical video behavior evaluation had been carried out without knowledge of the history and presenting complaint and (2) direct gastric examination had confirmed gastric disease status at the time. Twenty-four of the thirty cases showed gastric discomfort behavior, and all twenty-four had either gastric ulcers (n = 21) and/or gastric impaction (n = 3). Of the six cases not showing gastric discomfort behaviors, four were free of gastric disease, while two had mild lesions. Comparing horses with and without gastric disease, gastric discomfort behaviors were reported in 24 of the 26 (92%) with gastric ulcers or gastric impaction, compared to none of the four gastric disease-free horses. Although a larger prospectively designed study is needed to confidently estimate the sensitivity and specificity or the associations of behavior with the type or severity of gastric disease, these results confirm our long-held clinical impression of a behavioral signature for gastric discomfort in the horse.

Multimodal Longitudinal Optical Imaging Reveals Optic Neuritis Preceding Retinal Pathology in Experimental Autoimmune Encephalomyelitis.

Inflammatory demyelinating diseases of the CNS, chief among them multiple sclerosis (MS), are a major cause of disability in young adults. Early manifestations of MS commonly involve visual dysfunction, which is often caused by optic neuritis and is accompanied by quantifiable structural changes of the anterior visual pathway. Retinal optical coherence tomography (OCT) has emerged as an important tool for clinical assessment of these structural alterations, but the underlying pathobiological mechanisms and temporal dynamics are yet poorly understood at a cellular level. Using the experimental autoimmune encephalomyelitis (EAE) model of MS in fluorescent reporter mouse strains for neuronal function and innate immune cells, we use a unique combination of retinal intravital 2-photon microscopy (2PM) and OCT. In this fashion, we elucidate the spatiotemporal interplay of functional and structural retinal changes over the course of 1 month after EAE induction, with histopathologic imaging validating main results. While all mice display histologic signs of optic neuritis early after EAE induction and independently of motor symptom severity, retinal signs of neuronal stress and parenchymal immune activation spike well after clinical peak of disease, with no signs of lasting structural damage appearing within 1 month after EAE induction. Thus, local retinal endpoints appear to be functions of downstream axonal damage rather than of immediate immune activation directed at the retina. However, as early as 1 week after EAE induction, retinal 2PM can detect recruitment of perivascular immune cells towards the optic nerve (ON), providing the earliest sign of disease activity in otherwise clinically inconspicuous mice. Our work identifies the recruitment of CX3CR1+ cells to the ON as an early sign of disease underlining the importance of combined structural and functional retinal imaging for the spatiotemporal characterization of neuroinflammatory and neurodegenerative processes. It further proposes retinal phagocyte orientation, morphology, and abundance as potential surrogate markers for neurodegenerative activity.

Application of data mining for diagnosis of ENT diseases using the Naïve Bayes method with genetic algorithm feature selection

Ear, nose, and throat (ENT) disease is a disorder that occurs in the eustachian tube in one of the organs, be it the ear, nose, or throat. Early signs of ENT disease include sore throat, painful swallowing, swollen and red tonsils, runny nose, nosebleeds, blocked nose, discharge from the ears, and others. To determine the diagnosis, it is necessary to carry out a physical examination of the ears, nose, and throat as recommended by an expert, namely an ENT doctor. The research carried out was implementing data mining for the diagnosis of ENT diseases using the Naïve Bayes (NB) method. This method was chosen because it can increase the accuracy, efficiency, and accessibility of health services and is also easy to understand and apply to classify ENT disease symptom data. The NB method was used to build an ENT diagnosis classification model and the model performance was evaluated using accuracy, precision, and recall metrics. To increase the accuracy of the NB algorithm predictions, feature selection using a genetic algorithm can be used. Genetic algorithms can help select the most relevant and significant features, improving the accuracy of NB models by eliminating irrelevant or noisy features. By applying this method, predictions for ENT diseases can be produced with an accuracy of 95.67%.

Hepatitis B Care and Treatment in Zanzibar, Tanzania: A Demonstration Project Following 2015 WHO Treatment Guidelines, 2017-2021.

Zanzibar, a low-resource semiautonomous region of Tanzania, has an estimated prevalence of hepatitis B virus (HBV) infections of 3.6%. To assess the feasibility of care and treatment, a 5-year hepatitis B demonstration project was implemented in Zanzibar during January 2017-December 2021, following the 2015 WHO HBV care and treatment guidelines. Participants included adults (aged ≥ 18 years) who tested positive for HBV surface antigen and tested negative for HIV and hepatitis C antibody. Participants were examined for clinical signs of liver disease and testing was conducted at baseline to assess treatment eligibility and every 6-12 months thereafter. Tenofovir disoproxil fumarate (TDF) was provided at no cost to treatment-eligible participants. Clinical and laboratory data were analysed to assess improvement in proximal disease outcomes. Among 596 participants enrolled, the median age was 32 years (IQR 26-39) and 365 (61%) were male. Of those enrolled, 268 (45%) returned for ≥ 1 follow-up visit, with a median of 511 days of follow-up. Overall, 58 patients initiated treatment: 15 met treatment criteria based on liver cirrhosis alone; 13 by APRI > 1.5; among those with HBV DNA results, six met criteria based on HBV DNA levels and ALT activity; 24 met ≥ 2 criteria. Significant decreases in ALT activities, APRI scores and HBV DNA levels were observed among those treated. This hepatitis B care and treatment programme was demonstrated to be feasible in a low-resource setting. Despite challenges, testing and linkage to care is critical to decrease the global burden of hepatitis B.

The Art of Dermatology: Lessons Learned from Master Morphologist, Dr. Irwin Braverman.

In dermatology, the art and skill of morphologic assessment is key to generating logical differential diagnoses and understanding disease pathogenesis. Dr. Irwin M. Braverman, Professor Emeritus of Dermatology at the Yale School of Medicine, is a master morphologist and his book, Skin Signs of Systemic Disease, provided key insights into the relationships between cutaneous lesions and internal disease. In an interview with Dr. Braverman, he stressed the importance morphology plays in how dermatologists diagnosis skin disorders. From Dr. Braverman, we learned an approach to the study of morphology through the lens of an art connoisseur, in addition to how to appreciate subtle clues that suggest a diagnosis and how examination of the skin brings us closer to understanding our patient, what ails them, and how we can heal them.

Associations of Co-exposure to Polycyclic Aromatic Hydrocarbons and Vitamin D with Early Lung Dysfunction: Mediating Roles of Metabolic Score-Visceral Adiposity Index

BackgroundPreserved ratio impaired spirometry (PRISm) and airflow obstruction are recognized as critical early signs of chronic obstructive pulmonary disease (COPD). While these conditions arise from concurrent exposure to toxicants and essential nutrients, how vitamin D modifies the pulmonary toxicity induced by polycyclic aromatic hydrocarbons (PAHs) and the metabolic mechanisms involved is still unclear. MethodsBased on the National Health and Nutrition Examination Survey (NHANES) 2007-2012, data on urinary PAH metabolites (ΣOH-PAHs), serum vitamin D metabolite levels [Σ25(OH)D], and pulmonary function tests [forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC] from 2189 participants, including 369 subjects with early lung dysfunction, defined as PRISm or airflow obstruction. Multiple metabolic disorder indicators were calculated using biochemical markers. The interaction effects between vitamin D and PAHs were evaluated using multiple linear and logistic regression models. Causal mediation analyses and structural equation modeling were employed to investigate the mediating roles of metabolic indicators. ResultsPAHs and vitamin D had opposite effects on lung function parameters [FEV1: β (95 CIs) = -0.01 (-0.02, -0.01) vs. 0.01 (0.01, 0.04); FVC: β (95 CIs) = -0.01 (-0.02, 0.01) vs. 0.04 (0.01, 0.06)] and risk of early lung dysfunction [OR (95 CIs) = 1.22 (1.06, 1.40) vs. 0.52 (0.37, 0.73)]. Decreased associations of ΣOH-PAHs with FEV1, FVC, and early lung dysfunction, as well as with metabolic score-visceral adiposity index (MSV) were visualized with increased Σ25(OH)D among subjects with body mass index (BMI) < 28kg/m2. Furthermore, 2.18%, 18.20%, 5.70%, and 4.70% of the associations of co-exposure to ΣOH-PAHs and Σ25(OH)D with FEV1, FVC, FEV1/FVC, and early lung dysfunction disease were mediated by MSV. ConclusionsOur findings indicated that vitamin D antagonizes the hazardous effects of PAHs on early lung dysfunction by metabolic alteration, providing new insight into the identification of the underlying high-risk populations and accessible prevention and intervention measures for attenuating PAH-induced lung dysfunction.

Evaluating gait and postural responses to subthalamic stimulation and levodopa: A prospective study using wearable technology.

The efficacy of subthalamic stimulation on axial signs of Parkinson's disease (PD) is debated in the literature. This study delves into the dynamic interplay of gait and posture, specifically probing their nuanced response to subthalamic stimulation and levodopa. We used wearable sensor technology to examine alterations in the spatiotemporal parameters of gait and posture in individuals with PD before and 6 months after subthalamic deep brain stimulation (STN-DBS) surgery. Thirty-three subjects with PD were evaluated in two pre-operative and four post-operative conditions comprising OFF/ON medication and stimulation states. Standardized response mean (SRM) values were calculated to assess treatment responsiveness. Significant improvements in spatiotemporal gait parameters, including speed, stride length, cadence, and turning, were observed following STN-DBS surgery. Quantitatively, stimulation outperformed levodopa in enhancing gait speed, stride length, and turning, as indicated by SRM. Levodopa moderately improved stride time variability and asymmetry, while stimulation alone demonstrated limited efficacy. Postural parameters exhibited minimal change following STN-DBS, although stimulation showed a slight benefit in certain postural aspects. Our findings suggest positive effects of stimulation and levodopa on gait and postural parameters, with STN-DBS demonstrating superior efficacy in enhancing gait speed, stride length, and turning. However, gait variability remains unaddressed by current therapies, highlighting the need for novel treatments targeting regions beyond the basal ganglia.

CHARACTERISTICS OF RELATIONSHIPS BETWEEN BIOCHEMICAL INDICATORS OF CORD BLOOD OF NEWBORNS FROM MOTHERS IN THE RISK GROUP FOR THE DEVELOPMENT OF HEMOLYTIC DISEASE OF NEWBORNS

A hemolytic disease of the newborn may occur when the mother and fetus are incompatible according to the AB0 system or the Rh factor. Hemolytic disease is primarily observed in instances where the mother has blood group 0(I) according to the AB0 system, and in the fetus or newborn, according to the degree and frequency of inheritance, it is A(II), B(III). It is the most prevalent manifestation of the newborn nosology, with the initial stage being growth itself, and the level of total bilirubin (its indirect fraction). It is probable that other clinical and biochemical indicators undergo direct metabolic changes in response not only to the state of progressive hyperbilirubinemia, but also as an adaptive mechanism even in the absence of hemolytic disease in children of this group. The aim of the study. To conduct an analysis of the relationships between the biochemical indicators of umbilical cord blood from mothers with 0(I) blood group and with a negative Rh(D) factor, regardless of the blood group, without signs of hemolytic disease (HDN). Research materials and methods. This work involved the analysis of 30 umbilical cord blood samples, as well as the determination of the infant group (according to the AB0 system) and rhesus blood affiliation. The objective was to assess the main biochemical indicators of the newborn's functional state. The analysis included total and direct bilirubin, total protein, albumin, the calculation of the albumin-globulin coefficient, glucose, urea, creatinine, and the activity of a group of enzymes (ALT, AST, γ-GT, AF, total LDH (LDHtotal)). The statistical calculation of the obtained results was carried out using the Pearson correlation test (rxy). Group comparisons were carried out using the Wilcoxon-Mann-Whitney-Test (for the coincidence of the Rhesus characteristics of maternal and cord blood) and the The Kruskal–Wallis test for comparing the average values ​​of three or more samples (for the coincidence of maternal and cord blood groups when inheriting this characteristic). The ratio of groups and rhesus was evaluated according to Fisher's comparative test (F-distribution). Research results and their discussion. In the correlation analysis of the obtained data, a positive correlation was noted according to the Pearson test between the level of albumin and total protein (rxy=0.867, p=0.000). In the format of nitrogenous exchange, probable changes are also observed between the concentration of urea and total protein (p=0.023), between urea and albumin (p=0.033), and between creatinine and urea (p=0.025). Our studies show positive correlations between the activity of AF and AST (rхy=0.914, р=0.000), between LDHtotal and AST (rхy=0.637, р=0.000), as well as between LDHtotal and AF (rхy=0.517, p=0.004). All these indicators are important for a comprehensive assessment of biochemical homeostasis. It was found that the inheritance from mother to child of the rhesus and group traits also affects the value of ALT, AST, creatinine. Concusions. The analysis of umbilical cord blood indicators in a small group of samples (30) indicates probable changes and correlational relationships between them. To enhance the reliability and significance of the data, we intend to expand the number of samples under study. This will enable us to either substantiate or invalidate the current findings and, in due course, establish reference values for the Bukovyna region.

ANALYSIS OF REGIONALLY METASTATIC CERVICAL CANCER ACCORDING TO DATA FROM THE SAMARKAND REGION OF THE REPUBLIC OF UZBEKISTAN

Today, cervical cancer is the most important global medical and social problem. Purpose of the study. To study the incidence of cervical cancer and analyze the results of treatment of stage III-IV disease in the Samarkand region. Material and methods. The study was conducted on the basis of the Samarkand branch of the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Republic of Uzbekistan. The collection of research data included analysis of outpatient cards and anamnesis of patients admitted with the diagnosis of regionally metastasized forms of cervical cancer, data of patients with malignant neoplasms and advanced cases of malignant neoplasms - an accounting and reporting form. Interpretation work was carried out by age categories. At the same time, data from histologic and cytologic reports in the control group of cervical cancer stages III - IV, treated between 2020 and 2022, were used and processed. Results of the study. The reason for the first visit to the gynecologist at the time of diagnosis is mainly pain in the lower abdomen and lower back, bloody discharge from the genital tract on non-menstrual days and after contact, which are signs of advanced disease. The obstetric history revealed that 56 (53.3%) women did not consult a gynecologist at all after their last childbirth, and all patients had one to five medical abortions. Thirty-eight (36.2%) patients of early reproductive age were registered with an endocrinologist with a diagnosis of diffuse goiter. In 46% of the patients the menarche occurred at the age of 12-13 years, in 50% of the patients at the age of 14-16 years, and in 4% at the age of 18-19 years. Conclusion. The main goal of modern radiotherapy for cervical cancer today is radiation therapy without complications, elimination of relapse, and prolongation of survival. Our research continues in this direction.

Subclinical myocardial dysfunction of the left ventricular in patients with systemic lupus erythematosus

The aim – to study the frequency of left ventricular (LV) myocardial dysfunction and its relationship with disease activity in patients with systemic lupus erythematosus (SLE).Materials and methods. The study included 100 patients with SLE who met the criteria of SLICC/ACR 2012, 87% were women, the average age was 33 [25; 40] years, the average duration of the disease was 1 [1; 9] year, patients with varying degrees of activity according to SLEDAI-2K (low/moderate/high) – 30/45/25 (30%/45%/25%). All the subjects had not previously received biological therapy and had no previously diagnosed cardiovascular diseases and other rheumatic diseases. All patients received glucocorticoids (GCs) and hydroxychloroquine therapy in different dosages depending on the severity of the disease, according to the standards recommended by the Association of Rheumatologists of Russia from 2021. Methotrexate was received by 6% of patients, azathioprine – 14%, cyclophosphamide – 3%, nonsteroidal anti-inflammatory drugs – 81.2%. The control group consisted of 20 healthy individuals, having no signs of rheumatic diseases and CVD comparable in age and gender. All the subjects underwent echocardiography (ECHO) with tissue dopplerography and left ventricle global longitudinal strain (LV GLS) assessment by speckle tracking.Results. Violation of LV GLS was observed in 65 (65%) patients with SLE. In the SLE group, compared with the control group, a significantly more damaged LV GLS was revealed. In all patients with impaired diastolic function of the left ventricular myocardium, deterioration of LV GLS parameters is observed. Impairment of LV GLS correlated with clinical and immunological parameters in patients with SLE: the degree of SLE activity according to SLEDAI-2K (r=0.219), the level of antibodies to double-stranded DNA (a/b to ds-DNA) (r=0.316), the C3 level of the complement component (r=–0.389), the C4 level of the complement component (r=–0.238), the hemoglobin level (r=–0.255), the number of red blood cells (r=–0.286), the level of C-reactive protein (r=–0.284) and CRP (r=–0.927). Also, patients with SLE with diagnosed nephritis (n=26) had a significant violation of LV GLS parameters.Conclusions. In patients with SLE, according to ECHO using the Speckle tracking technique, violation of LV GLS occurs with a high frequency (65%). Violation of LV GLS parameters is associated with SLE activity, immunological and hematological disorders. In all patients with impaired diastolic function of the left ventricular myocardium, LV GLS was obviously decreased. The presence of lupus nephritis is associated with a significant violation of the GLS parameters.

Sporadic Burkitt Lymphoma First Presenting as Painful Gingival Swellings and Tooth Hypermobility: A Life-Saving Referral

Background: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma (NHL), subdivided into endemic, sporadic, and immunodeficiency-associated forms. While jaw lesions are common in endemic BL, they are infrequent in sporadic cases, only rarely constituting the first manifestation of the disease. The aim of this study is to present a rare pediatric case of sporadic BL first manifesting as gingival swellings and tooth hypermobility and provide a review of all the published sporadic BL case reports as the first sign of disease. Case report: An 11-year-old Caucasian female was referred for the evaluation of hypermobility of posterior lower teeth, associated with painful gingival swellings of 20 days duration. Clinical examination revealed right facial asymmetry and bilateral prominent swellings of the posterior lower gingiva. A panoramic radiograph revealed ill-defined radiolucent lesions in the posterior mandible bilaterally. On computed tomography, soft-tissue masses were identified along the mandibular ramus extending into the maxillary sinus bilaterally. The histopathologic and immunohistochemical analyses of the lesions led to a diagnosis of Burkitt lymphoma (BL). The patient underwent a full staging work-up, revealing bone marrow involvement and widespread disease. A multi-chemotherapy regimen was initiated with the regression of oral lesions and symptoms within a few weeks and complete disease remission after nine chemotherapy cycles. The patient remains free of disease 11 years later. Conclusions: This case underscores the critical importance of the timely diagnosis and life-saving referral of rapidly growing jaw lesions, which may represent the first sign of an underlying lymphoreticular malignancy with aggressive course, such as BL.

Differential Immunological Responses of Adult Domestic and Bighorn Sheep to Inoculation with Mycoplasma ovipneumoniae Type Strain Y98

Bighorn sheep (BHS) populations have been reported to experience high levels of morbidity and mortality following infection with Mycoplasma ovipneumoniae. This contrasts with the subclinical presentation in domestic sheep (DS). Understanding this difference requires baseline knowledge of pre- and post-infection immune responses of both species. The present study identifies differences in leukocyte phenotypes between adult BHS and DS before and after intranasal inoculation with 1 × 108 Mycoplasma ovipneumoniae. Prior to inoculation, BHS were confirmed to have a higher abundance of leukocyte CD14 and serum concentrations of IL-36RA. In contrast, DS had a higher leukocyte abundance of CD16 in addition to previously observed integrin markers and CD172a, as well as greater serum TNF-α concentrations. Within 15 days of inoculation, BHS displayed signs of mild respiratory disease and M. ovipneumoniae DNA was detected on nasal swabs using a quantitative PCR; meanwhile, DS exhibited few to no clinical signs and had levels of M. ovipneumoniae DNA below the standard curve threshold. Immunologic markers remained relatively consistent pre- and post-inoculation in DS, while BHS demonstrated changes in the peripheral leukocyte expression of CD172a and CD14. Circulating serum IL-36RA decreased and CXCL10 increased within BHS. These findings highlight significant differences in cellular immunity between BHS and DS, raised and housed under similar conditions, prior to and following inoculation with M. ovipneumoniae.

Limbic system synaptic dysfunctions associated with prion disease onset

Misfolding of normal prion protein (PrPC) to pathological isoforms (prions) causes prion diseases (PrDs) with clinical manifestations including cognitive decline and mood-related behavioral changes. Cognition and mood are linked to the neurophysiology of the limbic system. Little is known about how the disease affects the synaptic activity in brain parts associated with this system. We hypothesize that the dysfunction of synaptic transmission in the limbic regions correlates with the onset of reduced cognition and behavioral deficits. Here, we studied how prion infection in mice disrupts the synaptic function in three limbic regions, the hippocampus, hypothalamus, and amygdala, at a pre-clinical stage (mid-incubation period) and early clinical onset. PrD caused calcium flux dysregulation associated with lesser spontaneous synchronous neuronal firing and slowing neural oscillation at the pre-clinical stage in the hippocampal CA1, ventral medial hypothalamus, and basolateral amygdala (BLA). At clinical onset, synaptic transmission and synaptic plasticity became significantly disrupted. This correlated with a substantial depletion of the soluble prion protein, loss of total synapses, abnormal neurotransmitter levels and synaptic release, decline in synaptic vesicle recycling, and cytoskeletal damage. Further, the amygdala exhibited distinct disease-related changes in synaptic morphology and physiology compared with the other regions, but generally to a lesser degree, demonstrating how different rates of damage in the limbic system influence the evolution of clinical disease. Overall, PrD causes synaptic damage in three essential limbic regions starting at a preclinical stage and resulting in synaptic plasticity dysfunction correlated with early disease signs. Therapeutic drugs that alleviate these early neuronal dysfunctions may significantly delay clinical onset.

Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS).

The Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR study showed that, despite not showing any clinical sign of disease, patients with Raynaud's and antinuclear antibodies and/or capillaroscopy abnormalities often progress to systemic sclerosis (SSc) within 5 years. We aimed to determine whether VEDOSS biosamples show biological SSc activity pre-clinically. Skin biopsies were histologically analysed. Dermal fibroblasts analysed by RT-qPCR and gel contraction assays. Sera were assayed by Luminex (CXCL10) or ELISA (ELF score). Healthy controls (HC) and SSc biosamples were used for controls. Overall, 114 consecutive VEDOSS patients were enrolled, of which 36 consented to have skin biopsies. Skin biopsies showed a variable but overall increased collagen staining and skin thickness, increased perivascular infiltrate of CD45 positive cells and CXCL10 expression. In vitro, VEDOSS dermal fibroblasts showed increased profibrotic gene expression and contractibility compared with HC. Increased serological CXCL10 (mean [SD]; 75.90 [107.80] vs HC 39.90 [26.27] pg/ml, p = 0.02) and ELF score was evident in VEDOSS compared with HC (8.19 [0.78] vs 8.55 [0.79], p = 0.04). In longitudinal analysis of a median of 27.5 (IQR 44.5) months, 14.9% of VEDOSS patients progressed to SSc. Baseline CXCL10 serum concentration was significantly higher in the VEDOSS patients that progressed (2-fold increase, p = 0.0071) and correlated with ELF score (R = 0.3096, p = 0.0065). Despite not fulfilling classification criteria, VEDOSS patients show SSc-linked fibrosis and immunity dysregulation both within the tissue and sera, supporting a biological diagnosis of disease and a window of opportunity to detect the biological pathways amenable for preventive intervention.

Stranded heavy fuel oil exposure causes deformities, cardiac dysfunction, and oxidative stress in marine medaka Oryzias melastigma using an oiled-gravel-column system.

Heavy fuel oil (HFO) stranded on the coastline poses a potential threat to the health of marine fish after an oil spill. In this study, an oiled-gravel-column (OGC) system was established to investigate the toxic effects of stranded HFO on marine medaka Oryzias melastigma. HFO 380# (sulfur content 2.9%) was chosen as one type of high sulfur fuel oil for acute toxicity tests. The marine medaka larvae were exposed to the OGC system effluents with oil loading rates of 0 (control), 400, 800, 1600, and 3200µg HFO/g gravel for 144h, respectively. Results showed that a prevalence of blue sac disease signs presented teratogenic effects, including decreased circulation, ventricular stretch, cardiac hemorrhage, and pericardial edema. Moreover, the treatments (800, 1600, and 3200µg oil/g gravel) induced severe cardiotoxicity, characterized by significant bradycardia and reduced stroke volume with an overt decrease in cardiac output. Additionally, the antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST) were significantly upregulated at 800-3200µg oil/g gravel except for a marked inhibition of CAT activity at 3200µg oil/g gravel. Furthermore, significantly elevated protein carbonyl (PCO) levels were detected, suggesting that the organisms suffered severe protein oxidative damage subjected to the exposure. Overall, stranded HFO 380# exposure activated the antioxidant defense system (up-regulated POD and GST activities) of marine medaka and disrupted CAT activity, which could result in an oxidative stress state (elevated PCO levels) and might further contribute to cardiac dysfunction, deformities, and mortality.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques.

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical-pathological changes associated with EBOV disease in this model.

Cribra orbitalia and Porotic hyperostosis on bone remains of the Bronze Age population from the Lower Volga region (search for the proliferation causes)

This study is devoted to defining the occurrence frequency of Cribra orbitalia and Porotic hyperostosis signs based on the data obtained and establishing the reasons for the spread of these pathological conditions in the study groups. The material for the study is series dating back to the Early, Middle and Late Bronze Ages from the Lower Volga region kurgan mounds. When analyzing bone remains, the occurrence of porotic hyperostosis on the skull and cribra orbitalia was taken into account. To identify significantly significant differences in the incidence of pathological abnormalities, the groups were compared using non-parametric mathematical criteria. Statistical calculations were carried out in the StatSoft, Inc. shell. (2011) STATISTICA. As a result of the study, it was estab-lished that the factors influencing the occurrence of signs of hemolytic diseases in the study group could be en-demic malaria, helminths, as well as nutritional stress caused by systematic starvation, lack of vitamin C, folic acid, cobalamin and iron.

Investigating Clinical Risk Factors Contributing to the Recurrence of Idiopathic Granulomatous Mastitis

Background: Granulomatous mastitis (GM) is a chronic inflammatory disorder affecting breast tissue, with a high recurrence rate. Objectives: Regarding this impotence, this paper aims at proposing a retrospective approach to compile an extensive dataset of clinical information as well as to identify potential risk factors associated with GM recurrence. Methods: For this purpose, data on pathologically-confirmed cases of GM were retrospectively collected from the medical archives of the Shahid Beheshti Cancer Research Center, Iran, from March 2020 to February 2023. Then, the descriptive statistics were utilized to analyze demographic information, disease-related variables, patient-related variables, and details regarding treatment modalities. Evaluation of disease recurrence occurred 24 months following the initial GM diagnosis through clinical assessments, ultrasound, or mammography. Among the 100 accessible patients, 33 experienced recurrences within 24 months. Results: According to the obtained results, factors significantly associated with recurrence included body mass index (28.31 vs. 26.05), history of breastfeeding and its duration (22.44 months vs. 16.95 months) (90.9% vs. 72.7%), abortion, pain (72.7% vs. 46.3%), erythema nodosum (51.5% vs. 16.4%), hypertension (18.2% vs. 3%), thyroid disease (33.3% vs. 14.9%), rheumatologic disease (69.7% vs. 13.4%), dermal involvement (51.5% vs. 10.9%), joint involvement (85.9% vs. 39.4%), and the combined treatment modalities (45.5% vs. 11.9%). Moreover, the predictive model exhibited an overall accuracy of 83.3%. Conclusions: Finally, it can be concluded that abortion history, breastfeeding and its duration, combined treatment, pain, erythema nodosum, hypertension, thyroid or rheumatologic disease, dermatologic or joint signs, and Body Mass Index (BMI) could be the significant factors related to the recurrence of GM. Thus, special attention to these factors and management of baseline disease may have a predictive effect on the relapse of idiopathic granulomatous mastitis (IGM).