Spectrum Of Disease Research Articles

Antibiotic Resistance in Morganella morganii Species: Mechanisms, Prevalence and Clinical Implication

: Morganella morganii, a member of the Enterobacteriaceae family, has gained increasing recognition as an important pathogen due to its multidrug resistance. In addition to its intrinsic resistance, it carries various resistance genes and mobile genetic elements, facilitating the spread of resistance genes. M. morganii develops its mechanisms of resistance through different genetic elements, and its pathogenicity is supported by several virulence factors. Its rate of resistance has attended high levels in a number of studies. The global prevalence of M. morganii-associated infections is observed with nosocomial and healthcare-associated infections. The spectrum of diseases caused by M. morganii is diverse, ranging from sepsis and urinary tract infections, abscess, purple urine bag syndrome, chorioamnionitis, and cellulitis to wound infections and bacteremia. Mortality rates associated with M. morganii infections remain high, emphasizing the need for effective treatment strategies. Thus, this article aimed to provide an overview of the evolving multidrug resistance, resistance genes, risk factors, spectrum diseases, and clinical significance of M. morganii, and the challenges associated with the diagnosis and treatment of M. morganii infections.

The impact of alternate-day fasting on the salivary gland stem cell compartments in non-obese diabetic mice with newly established Sjögren's syndrome.

Intermittent fasting exerts a profound beneficial influence on a spectrum of diseases through various mechanisms including regulation of immune responses, elimination of senescent- and pathogenic cells and improvement of stem cell-based tissue regeneration in a disease- and tissue-dependent manner. Our previous study demonstrated that alternate-day fasting (ADF) led to alleviation of xerostomia and sialadenitis in non-obese diabetic (NOD) mice, a well-defined model of Sjögren's syndrome (SS). This present study delved into the previously unexplored impacts of ADF in this disease setting and revealed that ADF increases the proportion of salivary gland stem cells (SGSCs), defined as the EpCAMhi cell population among the lineage marker negative submandibular gland (SMG) cells. Furthermore, ADF downregulated the expression of p16INK4a, a cellular senescence marker, which was concomitant with increased apoptosis and decreased expression and activity of NLRP3 inflammasomes in the SMGs, particularly in the SGSC-residing ductal compartments. RNA-sequencing analysis of purified SGSCs from NOD mice revealed that the significantly downregulated genes by ADF were mainly associated with sugar metabolism, amino acid biosynthetic process and MAPK signaling pathway, whereas the significantly upregulated genes related to fatty acid metabolic processes, among others. Collectively, these findings indicate that ADF increases the SGSC proportion, accompanied by a modulation of the SGSC property and a switch from sugar- to fatty acid-based metabolism. These findings lay the foundation for further investigation into the functionality of SGSCs influenced by ADF and shed light on the cellular and molecular mechanisms by which ADF exerts beneficial actions on salivary gland restoration in SS.

Future applications of host direct therapies for infectious disease treatment.

New and emerging pathogens, such as SARS-CoV2 have highlighted the requirement for threat agnostic therapies. Some antibiotics or antivirals can demonstrate broad-spectrum activity against pathogens in the same family or genus but efficacy can quickly reduce due to their specific mechanism of action and for the ability of the disease causing agent to evolve. This has led to the generation of antimicrobial resistant strains, making infectious diseases more difficult to treat. Alternative approaches therefore need to be considered, which include exploring the utility of Host-Directed Therapies (HDTs). This is a growing area with huge potential but difficulties arise due to the complexity of disease profiles. For example, a HDT given early during infection may not be appropriate or as effective when the disease has become chronic or when a patient is in intensive care. With the growing understanding of immune function, a new generation of HDT for the treatment of disease could allow targeting specific pathways to augment or diminish the host response, dependent upon disease profile, and allow for bespoke therapeutic management plans. This review highlights promising and approved HDTs that can manipulate the immune system throughout the spectrum of disease, in particular to viral and bacterial pathogens, and demonstrates how the advantages of HDT will soon outweigh the potential side effects.

Disease spectrum and short-term outcomes of obstetric patients with cardiac disease admitted to an obstetric critical care unit in South Africa

Disease spectrum and short-term outcomes of obstetric patients with cardiac disease admitted to an obstetric critical care unit in South Africa

NMOSD and MOGAD: an evolving disease spectrum.

Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG)-a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future.

Changes in the Spectrum of Kidney Diseases: A 14-Year Kidney Biopsy Study from a Single Center

Changes in the Spectrum of Kidney Diseases: A 14-Year Kidney Biopsy Study from a Single Center

Changes in Iridotrabecular Contact and Intraocular Pressure after Phacoemulsification in Primary Angle-Closure Disease Spectrum.

To compare changes in the swept-source (SS) anterior-segment optical coherence tomography (AS-OCT) parameters and intraocular pressure (IOP) control after lens extraction in various spectra of primary angle-closure disease (PACD). A total 92 eyes from 92 patients with PACD who underwent lens extraction were included in the study. All patients underwent IOP measurement preoperatively and at 1 day, 1 week, and 1, 3, and 6 months postoperatively. SS AS-OCT was performed in all subjects preoperatively and 1 month postoperatively. All participants were divided into two groups depending on the presence of glaucomatous optic disc or visual field damage (group A, PAC suspect or PAC; group B, PAC glaucoma). The changes in IOP and anterior chamber angle parameters of SS AS-OCT of each group were compared. Regression analysis was performed to find factors associated with the degree of IOP reduction after lens extraction. Preoperatively, there was no significant difference in IOP between the two groups (16.3 ± 2.5 mmHg vs. 16.9 ± 3.2 mmHg, p = 0.297), but the number of glaucoma medications used was greater in group B (0.6 ± 1.0 vs. 2.0 ± 0.9, p < 0.001). Postoperatively, IOP was not significantly different, but the number of medications used was greater in group B (0.2 ± 0.7 vs. 0.9 ± 0.8, p < 0.001). Anterior chamber angle parameters including angle opening distance and trabecular-iris angle had a greater increase in group B after lens extraction. However, the residual iridotrabecular contact (ITC) index was significantly greater in group B (5.6 ± 7.0 vs 10.7 ± 12.1, p = 0.014). A greater change in the ITC index was related to a greater degree of IOP reduction (β coefficient, 0.429; p < 0.001). Eyes with PAC glaucoma had a greater residual ITC index after lens extraction compared with eyes of other PACD spectrum and required a greater number of glaucoma medications to maintain a similar level of IOP.

Association between self-reported child maltreatment and risk of hospital-treated infectious diseases in middle-aged and older adults: A UK Biobank cohort study.

This study aimed to explore the association between child maltreatment and hospital-treated infectious diseases in middle-aged and older adults. 145,151 participants aged 38-72 years from the UK Biobank between 2006 and 2010 were enrolled and interviewed. Child maltreatment included five types: physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse. Patterns of maltreatment were identified using latent class analysis (LCA). Cox regression was employed to estimate the associations between child maltreatment (number of types, individual types, and patterns) and infectious diseases. Further, we evaluated potential mediators using mediation analysis. Over a median follow-up of 13.4 years, 22,688 participants (12.26 per 1000 person-years) were hospitalized for an infectious disease. Participants reporting any maltreatment had elevated infectious diseases risk (HR 1.18, 95 % CI: 1.15-1.21) than those without maltreatment. A dose-response relationship was observed between the number of maltreatment types and infectious disease (one, HR 1.09 [95 % CI 1.06-1.13]; two, HR 1.17 [95 % CI 1.12-1.23]; three to five, HR 1.48 [95 %CI 1.41-1.55]; Ptrend < 0.001). Each type of maltreatment was associated with increased infectious diseases risk. LCA identified four patterns (low maltreatment, child neglect, child abuse, and poly-maltreatment), with those experiencing poly-maltreatment exhibiting the highest infectious diseases risk (HR 1.51, 95 % CI: 1.43-1.59). The association between child maltreatment and infectious diseases was mediated by C-reactive protein, phenotypic age acceleration, loneliness, psychiatric disorders, and unhealthy lifestyles. Child maltreatment may increase susceptibility to a broad spectrum of infectious diseases in adulthood, highlighting the need for early-life maltreatment prevention policies.

Analysis of the epidemiology and clinical characteristics of Epstein-Barr virus infection.

The Epstein-Barr virus (EBV) is responsible for a spectrum of human diseases and demonstrates a considerable prevalence among various populations. Advances in molecular epidemiological research have enhanced our comprehension of EBV-related pathologies. In this study, our objective was to examine the epidemiological profile and clinical features of EBV infection in Chongqing, China. We enrolled patients suspected of EBV-related diseases who were admitted to the First Affiliated Hospital of Chongqing Medical University between May 2013 and November 2022. Inclusion criteria were based on those who underwent EBV-specific immunofluorescence or plasma EBV-DNA testing. Among 13 584 inpatients, the overall seropositivity rates for EBNA-1-IgG, EBV-VCA-IgM, EBV-EA-IgG, EBV-EA-IgA, EBV-VCA-IgA, and EBV-DNA were 91.89%, 7.22%, 18.00%, 16.19%, 30.78%, and 18.00%, respectively. The seropositivity rate for EBNA-1-IgG steadily increased with age. The seropositivity rate for VCA-IgM, an indicator of acute EBV infection, was highest in patients aged 11-20 years at 26.41%, decreasing to 2%-6% in older patients. Additionally, among 205 outpatients, the EBV-DNA positivity rate was 14.15%. In 3670 individuals from health check-up centers, the seropositivity rates for EBV-EA-IgA and EBV-VCA-IgA were 11.96% and 28.09%, respectively, and the EBV-DNA positivity rate was 11.92%, all of which were lower than those in inpatients. Among the 762 EBV-DNA positive inpatients, adults aged 31-40 years were the least affected, with a seropositivity rate of 12.00%, which increased with age. The most common diseases associated with primary EBV infection were infectious mononucleosis (IM) (35.49%), followed by EBV infection (14.15%) and pneumonia (7.19%). The most common diseases associated with EBV reactivation were pneumonia (16.80%), nasopharyngeal carcinoma (NPC) (11.02%), and autoimmune diseases (7.04%). Patients with hemophagocytic lymphohistiocytosis (HLH) had the highest viral load, significantly higher than those with NPC, pneumonia, and liver cirrhosis. This large-scale retrospective study explores the epidemiological characteristics and disease spectrum of EBV infection across all age groups. The findings contribute to the improvement of diagnostic and management strategies for EBV infection.

Successful generation of fully human, second generation, anti-CD19 CAR T cells for clinical use in patients with diverse autoimmune disorders

BackgroundB-cell targeting chimeric antigen receptor (CAR) T-cell therapies, which lead to profound B-cell depletion, have been well-established in hematology-oncology. This deep B-cell depletion mechanism has prompted the exploration of their use in B-cell driven autoimmune diseases. We herein report on the manufacturing of KYV-101, a fully human anti-CD19 CAR T-cell therapy, derived from patients who were treated across a spectrum of autoimmune diseases. MethodsKYV-101 was manufactured from peripheral blood-derived mononuclear cells of 20 patients across 7 autoimmune disease types (neurological autoimmune diseases, n=13; rheumatological diseases, n=7). Patients ranged from 18–75 years of age. Duration of disease ranged from <1–23 years since diagnosis. Patients were heavily pretreated, and most were refractory to prior immunosuppressive treatments. Apheresis was collected across 9 sites, cryopreserved, and shipped to the manufacturing facility. Healthy donor apheresis samples were collected for manufacturing comparison. Manufacturing was performed using the CliniMACS Prodigy system. Cells were enriched for CD4+/CD8+ T cells, transduced with a 3rd generation lentiviral vector encoding the CAR, expanded in vitro, and harvested. Percent cell viability, T-cell purity, cellular expansion, and transduction efficiency were assessed. Activity was assessed using cytokine release assays for KYV-101 CAR T cells co-cultured with different CD19+/– target cell lines. ResultsKYV-101 was successfully manufactured for 100% of patients. Transduced cell populations were highly viable, with expansion ranging from 11–66 fold at Day 8, and were comparable across disease types. Healthy donor-derived controls displayed similar expansion ranges. High CAR expression and transduction rates were observed, ranging between 37–84% with low variation in transgene copy number (2 to 4 per cell). Cell viability of the final KYV-101 drug product ranged from 87–97%. KYV-101 displayed robust CD19-dependent and effector dose-related release of the pro-inflammatory cytokine IFN-γ. ConclusionsKYV-101 manufacturing yielded a CAR T-cell product with high viability and consistent composition and functionality, regardless of disease indication, pre-treatment, and heterogeneity of the incoming material. Cryopreservation of the apheresis and final drug product enabled widespread distribution. These results support the robustness of the manufacturing process for the fully human KYV-101 anti-CD19 CAR T-cell therapy drug product for patients across diverse autoimmune disease types.

Harnessing RNA interference for the control of Fusarium species: A critical review.

Fusarium fungi are a pervasive threat to global agricultural productivity. They cause a spectrum of plant diseases that result in significant yield losses and threaten food safety by producing mycotoxins that are harmful to human and animal health. In recent years, the exploitation of the RNA interference (RNAi) mechanism has emerged as a promising avenue for the control of Fusarium-induced diseases, providing both a mechanistic understanding of Fusarium gene function and a potential strategy for environmentally sustainable disease management. However, despite significant progress in elucidating the presence and function of the RNAi pathway in different Fusarium species, a comprehensive understanding of its individual protein components and underlying silencing mechanisms remains elusive. Accordingly, while a considerable number of RNAi-based approaches to Fusarium control have been developed and many reports of RNAi applications in Fusarium control under laboratory conditions have been published, the applicability of this knowledge in agronomic settings remains an open question, and few convincing data on RNAi-based disease control under field conditions have been published. This review aims to consolidate the current knowledge on the role of RNAi in Fusarium disease control by evaluating current research and highlighting important avenues for future investigation.

The Spectrum of Biopsy-Proven Kidney Disease in People Living with HIV in Tertiary-Care Centers in Mexico City

The Spectrum of Biopsy-Proven Kidney Disease in People Living with HIV in Tertiary-Care Centers in Mexico City

Comparison of single shot and multishot diffusion-weighted imaging in 5-T magnetic resonance imaging for brain disease diagnosis.

Diffusion-weighted imaging (DWI) with single-shot echo-planar imaging (ssEPI) is a valuable tool for detecting acute brain lesions but does suffer from image distortions. Multishot echo-planar imaging (msEPI) is a technique for reducing such distortions. This study aimed to compare the image quality and diagnostic efficacy of ssEPI- and msEPI-DWI at 5.0 T for brain disease detection. This study retrospectively reviewed images of 107 consecutive patients with suspected brain diseases who underwent ssEPI- and msEPI-DWI at 5.0 T at the First Affiliated Hospital of University of Science and Technology of China from August 2023 to September 2023. Two radiologists independently graded image quality and measured the image distortion. Signal-to-noise ratio, contrast-to-noise ratio, and apparent diffusion coefficient (ADC) were calculated and compared between ssEPI- and msEPI-DWI. Image quality scores were compared using the Wilcoxon test and other continuous variables by the paired t-test. The diagnostic accuracy of ADC values in distinguishing lesions from normal-appearing tissues was measured with the area under the curve (AUC). Image quality evaluation and distortion analysis revealed that msEPI-DWI significantly outperformed ssEPI-DWI (two-sided P<0.001). No significant difference was observed in signal-to-noise ratio, contrast-to-noise ratio, or ADC values between msEPI- and ssEPI-DWI (two-sided P≥0.601). The ADC values of msEPI- and ssEPI-DWI showed strong correlations for both lesions (r=0.97) and contralateral normal tissues (r=0.91) (two-sided P<0.001). Compared to those of the contralateral white matter, ADC values of low-grade gliomas (LGGs) were significantly higher [ssEPI-DWI: 1,119.9±273.1 vs. 805.1±73.9; msEPI-DWI: 1,196.2±355.6 vs. 757.3±98.0 (unit: ×10-6 mm2/s)], while the ADC values of acute cerebral infarction (ACI) lesions were significantly lower [ssEPI-DWI: 603.9±273.2 vs. 888.9±212.0; msEPI-DWI: 538.0±281.2 vs. 905.0±188.9 (unit: ×10-6 mm2/s)] (two-sided P≤0.003). The AUCs for detecting LGGs were excellent for both ssEPI-DWI [AUC =0.934; 95% confidence interval (CI): 0.84-1.00] and msEPI-DWI (AUC =0.944; 95% CI: 0.86-1.00) (two-sided P<0.001; two-sided DeLong test: P=0.833). As compared to ssEPI-DWI, msEPI-DWI, when performed at 5.0 T, demonstrated superior image quality and less anatomical distortion in a wide spectrum of brain diseases and showed promising diagnostic performance for LGGs and ACI. In the future, msEPI-DWI at 5.0 T could become clinically routine in the diagnosis and grading of brain disorders.

681P A novel COL11A1 variant in a child with neuromuscular findings: expanding the genotypic and phenotypic spectrum of COL11A1-related disease

681P A novel COL11A1 variant in a child with neuromuscular findings: expanding the genotypic and phenotypic spectrum of COL11A1-related disease

In silico models for the screening of human transthyretin disruptors

The use of New Approach Methodologies (NAMs), such as Quantitative Structure-Activity Relationship (QSAR) models, is highly recommended by international regulations to speed up hazard and risk assessment of Endocrine Disruptors, which are known to be linked to a wide spectrum of severe diseases on humans and wildlife. A very sensitive target for these chemicals is the thyroid hormone system, which plays a key role in regulating metabolic and cognitive functions. Several chemicals have been demonstrated to compete with the thyroid hormone thyroxine (T4) for binding to human thyroid hormone distributor protein transthyretin (hTTR). In this work, we generated three new datasets composed by T4-hTTR competing potencies of more than 200 heterogeneous chemicals measured by three different in vitro assays. These datasets were used for the development of new regression QSAR models. The best models were thoroughly validated by internal and external validation procedures. The mechanistic interpretation of the selected molecular descriptors provided information on structural features which are relevant to characterise hTTR binders, such as the presence of hydroxylated and halogenated aromatic rings. PCA analysis was used to rank the studied chemicals according to their increasing T4-hTTR competing potency. Hydroxylated and halogenated bicyclic aromatic compounds are ranked as the strongest hTTR binders. The new QSARs are useful to screen potential Thyroid Hormone System-Disrupting Chemicals (THSDCs), and to support the identification of sustainable alternatives to hazardous chemicals.

Genetics behind the Phenotypic Spectrum of Polycystic Kidney Disease

Genetics behind the Phenotypic Spectrum of Polycystic Kidney Disease

Pathologic Spectrum of Kidney Disease Associated with Snake Bites

Pathologic Spectrum of Kidney Disease Associated with Snake Bites

Role of gut microbiota and immune cells in metabolic-associated fatty liver disease: clinical impact.

In 2020, a revised definition of fatty liver disease associated with metabolic dysfunction (MAFLD) was proposed to replace non-alcoholic fatty liver (NAFLD). Liver steatosis and at least one of the three metabolic risk factors, including type 2 diabetes, obesity, or signs of metabolic dysregulation, are used to diagnose MAFLD. MAFLD, similarly to NAFLD, is characterized by a spectrum of disease ranging from simple steatosis to advanced metabolic steatohepatitis with or without fibrosis, and may progress to cirrhosis and liver cancer, including increased risk of other critical extrahepatic diseases. Even though the pathophysiology of MAFLD and potential therapeutic targets have been explored in great detail, there is yet no Food and Drug Administration approved treatment. Recently, gut microbiome-derived products (e.g., endotoxins and metabolites) involved in intestinal barrier disruption, systemic inflammation, and modification of intrahepatic immunity have been associated with MAFLD development and progression. Therefore, different strategies could be adopted to modify the gut microbiome to improve outcomes in early and progressive MAFLD. Here, we provide an overview of mechanisms that may link the gut microbiome and immune response during the onset of liver steatosis and progression to steatohepatitis and fibrosis in patients with MAFLD. Finally, gut microbiota-based approaches are discussed as potential personalized treatments against MAFLD.

SYNDROME DE DENYS - DRASH : A PROPOS DUN CAS

Denys-Drash syndrome (DDS) consists of a triad of pseudo-hermaphroditism, Wilms tumor and nephropathy. The condition may manifest as a complete triad or an incomplete form, with any or a combination of the above features. The characteristic glomerular abnormality of DDS is diffuse mesangial sclerosis.DDS is a spectrum of diseases with phenotypic heterogeneity. The clinical course is unpredictable despite a similar genotype.There is no single clinical guideline for the optimal management of patients with DDS, due to the impossibility of accurately predicting the course of each affected individual. Similarly, there is no consensus on the advisability of removing native kidneys in DDS patients with nephropathy that has progressed to End Stage Renal Disease. Ultimately, clinical practice is guided by the availability of resources.We report in this work a suspected case of DDS, which was lost within 24 hours of hospitalization.

Risk Prediction in Diverticulitis

AbstractAcute diverticulitis is a common sequela of colonic diverticulosis that often poses a significant dilemma for surgeons and patients considering surgical management of the disease. Importantly, the decision to recommend surgery for patients with diverticular disease hinges on identifying those who will benefit most in terms of preventing future disease-related complications. This review focuses on identifying patient risk factors that are predictive of onset of diverticulitis, recurrence of disease, and progression to complicated disease, such as abscess, fistula, or stricture, and aims to assist clinicians with counseling patients who are considering surgery versus medical management. Specifically, a variety of modifiable and nonmodifiable risk factors have been identified across several studies that have strong associations with the development of diverticulitis, recurrence of uncomplicated disease, and progression to complicated disease. A handful of clinical scores have been described to guide surgeons and patients on their individual risk; however, none have been adopted into wider clinical practice. A novel polygenic risk score does show promise in potentially fulfilling this role. Nevertheless, there is significant room for innovation and development of new methods to risk-stratify patients presenting with the spectrum of diverticular disease.