Severe Disease Symptoms Research Articles

Berkeleyomyces rouxiae—A Pathogen Causing the Black Root Rot of Tobacco

Black root rot is a dangerous disease affecting many crops. It is caused by pathogens formerly known as Thielaviopsis basicola and then reclassified as two cryptic species, Berkeleyomyces basicola and B. rouxiae. The aim of this study was to perform species identification, morphological characterization, and pathogenicity tests for fungal isolates obtained from tobacco roots with black root rot symptoms in Poland. DNA sequences of the three regions (ITS, ACT, MCM7) were highly similar to the sequences of B. rouxiae deposited in the NCBI database. Phylogenetic analysis confirmed the assignment of the obtained isolates to this species. The cultures of four representative isolates (namely OT2, OT3, WPT7, WPT8) showed a similar structure and gray/brown color of the mycelium, although their growth rate varied from 3.8 to 5.1 mm/day depending on the isolate. The sizes of the endoconidia and chlamydospores showed a considerable variation, although they fit within ranges previously described for B. rouxiae. Pathogenicity tests performed on young tobacco plants grown in the inoculated peat substrate revealed differences among the four isolates. WPT7 demonstrated the lowest level of aggressiveness for tobacco. In contrast, the remaining three isolates caused severe disease symptoms and significantly reduced shoot and root dry weights of the susceptible cultivar Virginia Joyner. A parallel pathogenicity test performed on cultivar VRG 10TL confirmed the effectiveness of black root rot resistance derived from Nicotiana debneyi.

Occurrence of atypical Pseudomonas viridiflava strains on different host plants in southern Italy

AbstractSince 1997, severe bacterial disease symptoms were observed during surveys carried out in farms with field‐grown Molfettese Catalogna chicory (Cichorium intybus var. sylvestre, Catalogna group), sugarloaf chicory (C. intybus var. porphyreum), curly type lettuce (Lactuca sativa var. crispa) cvs Langero and Aleppo, and safflower (Carthamus tinctorius) located in the Apulia and Basilicata regions of southern Italy. Convex colonies with yellowish mucoid material on hypersucrose medium (5% sucrose nutrient agar), producing fluorescent pigments on King's medium B, were isolated from all symptomatic plants. Based on conventional biochemical and nutritional tests, Biolog assays, and analysis of partial 16S rDNA and rpoB sequences, these atypical fluorescent Pseudomonas isolates were identified as Pseudomonas viridiflava. The pathogenicity of the isolates was ascertained by artificial inoculation on their respective original hosts. The analysis of rpoB gene sequences and RAPD‐PCR profiles showed a high genetic variability among the P. viridiflava isolates. To the best of our knowledge, this is the first report of bacterial diseases on horticultural crops caused by atypical strains of P. viridiflava in Italy and the first report of the bacterium on safflower. In addition, P. viridiflava is reported for the first time as a causal agent of leaf spot on potato (Solanum tuberosum). The economic importance of chicory and curly type lettuce in southern Italy and recent spread of atypical and highly virulent P. viridiflava strains require more extensive and careful phytosanitary surveillance, as well as an adjustment of sustainable crop protection management to cope with this new challenge.

Reevaluating Diabetes and COVID-19 outcomes using national-level data

PurposeUsing a US nationally representative survey of adults, we aimed to evaluate the association between prevalent diabetes and the uptake of COVID-19 testing, rate of positive testing and symptom severity. MethodsData were sourced from the 2020-2021 National Health Interview Survey. COVID-19 outcomes were defined as: (1) test uptake (2) test positivity (3) diagnosis of COVID-19 and (4) severe disease symptoms with a positive COVID-19 test result. We compared the prevalence of COVID-19 outcomes by diabetes status and examined their associations using multivariate adjusted logistic and ordered logistic regression models. ResultsThe prevalence of test uptake and test positivity were 50.7% and 9.4% in the US population, respectively. 10.3% were diagnosed with COVID-19 infection by health professionals. There were no statistically significant differences in the outcomes by diabetes status. However, individuals with diabetes were more likely to have severe symptoms. In adjusted regression model, we found no significant associations of diagnosed diabetes with all outcomes. ConclusionsOur findings contrast with prior evidence derived from hospitalized patients. Researchers and policy makers are encouraged to review the properties of data sources and their impact on public health recommendations, particularly in response to future pandemics.

Single-Nucleus and Spatial Transcriptomics Revealing Host Response Differences Triggered by Mutated Virus in Severe Dengue.

Dengue virus (DENV) infection causes various disease manifestations ranging from an asymptomatic state to severe, life-threatening dengue. Despite intensive research, the molecular mechanisms underlying the abnormal host responses and severe disease symptoms caused by evolved DENV strains is not fully understood. First, the spatial structure of mutant DENV was compared via in silico molecular modeling analysis. Second, employing single-nucleus and spatial RNA sequencing, we analyzed and verified transcriptome samples in uninfected, mild (NGC group), and severe (N10 group) liver tissues from murine models. In this study, we obtained a cumulatively mutated DENV-2 N10 with enhanced capability of replication and pathogenicity post 10 serial passages in Ifnra-/- mice. This variant caused severe damage in the liver, as compared with other organs. Furthermore, mutated DENV infection elicited stronger responses in hepatocytes. The critical host factor Nrg4 was identified. It dominated mainly via the activation of the NRG/ErbB pathway in mice with severe symptoms. We report on evolved N10 viruses with changes observed in different organisms and tissue. This evolutionary variant results in high replicability, severe pathogenicity, and strong responses in murine. Moreover, the host responses may play a role by activating the NRG/ErbB signaling pathway. Our findings provide a realistic framework for defining disturbed host responses at the animal model level that might be one of the main causes of severe dengue and the potential application value.

Influence of sleep quality, excessive daytime sleepiness, circadian features and motor subtypes on depressive symptoms in Parkinson's disease

ObjectivesThe diagnosis of Parkinson's disease (PD) is mainly based on the assessment of motor symptoms, although the influence of non-motor symptoms sometimes may be more significant on the patient's disability than the cardinal clinical signs of the disease. The predominant subtype of postural instability and gait disturbance is known to be associated with more severe non-motor symptoms of Parkinson's disease. Yet, the association between motor subtypes and specific mood symptoms remains understudied. The study aimed to analyze an association between sleep and chronotype signs, motor subtypes, with the severity of depressive symptoms in PD patients. MethodsWe have included 64 patients in the clinical study. The studied population was divided into the following groups: PIGD group – patients with PD and dominance of postural instability and gait disorders; non-PIGD group – patients with PD and dominance of tremor or intermediate motor subtype. We used the Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Munich Chronotype Questionnaire. ResultsPatients with the PIGD subtype have higher levels of depressive symptoms and excessive daytime sleepiness, poorer sleep quality, later sleep onset and mid-sleep, longer sleep latency, and sleep inertia. PIGD motor subtype (p < 0.001), poor sleep quality (p < 0.001), mid-sleep (p = 0.016), and sleep latency (p = 0.025) had a significant impact on the level of depression in univariate regression analysis. Still, only mid-sleep (p = 0.019) and poor sleep quality (p = 0.003) increased the probability of higher severity of depression in the multivariate model. ConclusionPoor sleep quality and later mid-sleep may be predictors of more severe depressive symptoms in PD.

The FERONIA-RESPONSIVE TO DESSICATION 26 module regulates vascular immunity to Ralstonia solanacearum.

Some pathogens colonize plant leaves, but others invade the roots, including the vasculature, causing severe disease symptoms. Plant innate immunity has been extensively studied in leaf pathosystems; however, the precise regulation of immunity against vascular pathogens remains largely unexplored. We previously demonstrated that loss of function of the receptor kinase FERONIA (FER) increases plant resistance to the typical vascular bacterial pathogen Ralstonia solanacearum. Here, we show that upon infection with R. solanacearum, root xylem cell walls in Arabidopsis thaliana become highly lignified. FER is specifically upregulated in the root xylem in response to R. solanacearum infection, and inhibits lignin biosynthesis and resistance to this pathogen. We determined that FER interacts with and phosphorylates the transcription factor RESPONSIVE TO DESICCATION 26 (RD26), leading to its degradation. Overexpression and knockout of RD26 demonstrated that it positively regulates plant resistance to R. solanacearum by directly activating the expression of lignin-related genes. Tissue-specific expression of RD26 in the root xylem confirmed its role in vascular immunity. We confirmed that the FER-RD26 module regulates lignin biosynthesis and resistance against R. solanacearum in tomato (Solanum lycopersicum). Taken together, our findings unveil that the FER-RD26 cascade governs plant immunity against R. solanacearum in vascular tissues by regulating lignin deposition. This cascade may represent a key defense mechanism against vascular pathogens in plants.

Population-level whole-genome sequencing of Ascochyta rabiei identifies genomic loci associated with isolate aggressiveness.

Ascochyta blight caused by the ascomycete Ascochyta rabiei poses a major biotic threat to chickpea (Cicer arietinum) industries worldwide and incurs substantial costs to the Australian multimillion-dollar chickpea industry in both disease control and yield loss. The fungus was introduced to Australia in the 1970s from an unknown source population and, within a few decades, successfully established in all Australian agroecological chickpea-growing regions. Although genetically highly clonal, a broad range of phenotypic variation in terms of aggressiveness exists among the Australian A. rabiei isolates. More recently, highly aggressive isolates capable of causing severe disease symptoms on moderate to highly resistant chickpea cultivars have increased in frequency. To identify genetic loci potentially associated with A. rabiei aggressiveness on Australian chickpea cultivars, we performed deep genome sequencing of 230 isolates collected from a range of agroecological chickpea-growing regions between 2013 and 2020. Population genetic analyses using genome-wide SNP data identified three main clusters of genetically closely related isolates in Australia. Phylogenetic analyses showed that highly aggressive phenotypes developed multiple times independently throughout the phylogeny. The results point to a minor contribution of multiple genetic regions and most likely epigenomic variations to aggressiveness of A. rabiei isolates on Australian chickpea cultivars.

Comparison between 1.5 and 3-Tesla MRI findings in Ménière's disease.

Introduction3 T-MRI of the inner ear has been used to identify the endolymphatic hydrops (EH) phenomenon, and less frequently 1.5 T-MRI. The aim of this study was to assess whether there was agreement between findings of EH at 1.5 T MRI and those obtained at 3.0 T MRI in patients clinically diagnosed with definite Meniere disease (MD).MethodsCross-sectional, blinded study was conducted in a tertiary neurotology ambulatory practice. Thirty patients with clinical diagnosis of unilateral definite MD was included. Two MRI exams (1.5 T and 3.0 T) were performed for each patient and were evaluated by two examiners (E1, E2) who were blinded to the symptomatic ear. An analysis of intra-and inter-examiner agreement was performed. It was determined whether there was an association between MRI findings and disease duration, symptom severity, and MD clinical stage.ResultsE1 found EH at 3 T-MRI in 26 (86.66%) patients and at 1.5 T-MRI in 25 (83.33%). E2 found EH in 25 (83.33%) patients in 3 T-MRI and in 22 (73.33%) at 1.5 T-MRI. The agreement between the examiners’ assessments in relation to the EH was high (0.844) for the 3 T MRI and substantial for the 1.5 T, both statistically significant. There was no statistically significant relationship between EH imaging findings and clinical disease severity and course.Discussion1.5 T and 3.0 T MRI images agreed regarding the findings of absence or presence of cochlear hydrops (CH) and vestibular hydrops (VH). The degrees of CH and VH found at 3.0 T MRI in symptomatic ear were not associated with clinical aspects and the stage of disease.

Oral Health Related Factors Predicting Severe COVID-19 Disease in Elderly Swedes.

To analyse different background factors that may serve as predictors for acquiring symptoms of severe COVID-19 disease. A postal questionnaire was sent to the total population of individuals born between 1942 (80 years, n = 6299) and 1932 (90 years, n = 1904) living in the Örebro and Östergötland counties, Sweden, in 2017 and repeated in 2022. Tentative predictive factors for self-reported severe COVID-19 disease were based on the responses from the 2017 questionnaire related to general and oral health and prior to the outbreak of the COVID-19 pandemic. Response rate to the main questionnaire in 2022 was 66% (5375/8203), and 577 reported having been sick with COVID-19 out of which 359 agreed to answer a separate questionnaire on COVID-19. This questionnaire was returned by 278/359 of the participants corresponding to a response rate of 77%. Information gleaned from the 2017 pre-COVID-19 survey revealed a relatively large number of associations between severity of subsequently self-reported COVID-19 disease and several diverse tentative related factors found in unadjusted regression analyses. Based on statistically significant correlations in the adjusted regression analysis, significant predictive factors (based on self-reports from 2017) for contracting severe COVID-19 were in decreasing order of odds ratios (OR): reported removable partial or complete denture usage (OR 6.2, CI 2.2-17.2); reported periodontal problems in the past year (OR 3.4, CI 1.1-10.4); and reported daytime dry mouth (OR 2.5, CI 1.2-5.2). Removable dentures, periodontal problems and daytime dry mouth were predictors for developing symptoms of severe COVID-19 disease.

Virome Characterization of Native Wild-Rice Plants Discovers a Novel Pathogenic Rice Polerovirus With World-Wide Circulation.

Pandemics originating from zoonotic viruses have posed significant threats to human health and agriculture. Recent discoveries have revealed that wild-rice plants also harbour viral pathogens capable of severely impacting rice production, a cornerstone food crop. In this study, we conducted virome analysis on ~1000 wild-rice individual colonies and discovered a novel single-strand positive-sense RNA virus prevalent in these plants. Through comprehensive genomic characterization and comparative sequence analysis, this virus was classified as a new species in the genus Polerovirus, designated Rice less tiller virus (RLTV). Our investigations elucidated that RLTV could be transmitted from wild rice to cultivated rice via a specific insect vector, the aphid Rhopalosiphum padi, causing less tiller disease symptoms in rice plants. We generated an infectious cDNA clone for RLTV and demonstrated systemic infection of rice cultivars and induction of severe disease symptoms following mechanical inoculation or stable genetic transformation. We further illustrated transmission of RLTV from stable transgenic lines to healthy rice plants by the aphid vector, leading to the development of disease symptoms. Notably, our database searches showed that RLTV and another polerovirus isolated from a wild plant species are widely circulating not only in wild rice but also cultivated rice around the world. Our findings provide strong evidence for a wild plant origin for rice viruses and underscore the imminent threat posed by aphid-transmitted rice Polerovirus to rice cultivar.

Ralstonia solanacearum (phylotype II) isolated from Rosa spp. in the Netherlands is closely related to phylotype II isolates from other sources in the Netherlands and is virulent on potato

AbstractIn 2018, during an annual survey in the Netherlands, Ralstonia solanacearum phylotype II (phy II) was found in asymptomatic greenhouse rose plants at three geographic locations. These findings were remarkable, since previous findings of Ralstonia sp. in rose always concerned Ralstonia pseudosolanacearum phylotype I (phy I). Therefore, no information was available on the virulence of R. solanacearum phy II on rose. In this study, R. solanacearum phy II isolates PD 7421 and PD 7394, isolated in 2018 from asymptomatic ornamental rose (Rosa spp.), were assessed for their virulence in two rose cultivars (“Armando” and “Red Naomi”) at two temperatures. No typical symptoms were observed for PD 7421 and PD 7394 on the two rose cultivars, irrespective of the temperature. However, latent infections upon inoculation of these isolates on rose did occur. R. solanacearum phy II is known as a major potato pathogen, where it causes brown rot. Whole genome multilocus sequence typing analysis demonstrated that the isolates from rose were closely related to R. solanacearum phy II isolates previously found in seed potato and surface water in the Netherlands. Because of this close genetic relatedness, the virulence of PD 7421 and PD 7394 was also assessed in potato plants, where both isolates caused severe disease symptoms on the shoots as well as the daughter tubers. This implies that rose can act as a reservoir for R. solanacearum phy II and, in this way, can potentially be involved in spreading this bacterium.

The identification of a key gene highlights macrocyclic ring’s role in trichothecene toxicity

Trichothecenes are toxins produced by certain species from several fungal genera, including Aspergillus, Fusarium, Isaria, Paramyrothecium, Stachybotrys, Trichoderma, and Trichothecium. These toxins are of interest because they contribute to the toxigenicity, plant pathogenicity, and/or biological control activities of some fungi. All trichothecenes have the same core (12,13-epoxytrichothec-9-ene or EPT) structure but can differ from one another by the presence or absence of a macrocyclic ring formed from polyketide and isoprenoid substituents esterified to carbon atoms 4 and 15 of EPT, respectively. Genes required for formation and some modifications of EPT have been elucidated, but almost nothing is known about genes specific to the formation of the macrocyclic ring. Therefore, we used genomic, transcriptomic, metabolomic, and gene deletion analyses to identify genes that are required specifically for the formation of the macrocyclic ring. These analyses identified one gene, TRI24, that is predicted to encode an acyltransferase and that is required for macrocyclic ring formation during biosynthesis of macrocyclic trichothecenes by the fungus Paramyrothecium roridum. In addition, a TRI24 deletion mutant of P. roridum caused less severe disease symptoms on common bean and had less antifungal activity than its wild-type progenitor strain. We propose that the reduced aggressiveness and antifungal activity of the mutant resulted from its inability to produce trichothecenes with a macrocyclic ring. To our knowledge, this is the first report of a gene required specifically for the formation of the macrocyclic ring of trichothecenes and that loss of the macrocyclic ring of trichothecenes can alter the biological activities of a fungus.Key points• TRI24 gene is found in all known macrocyclic trichothecene-producing fungi.• A tri24-deletion mutant exhibits a reduction in antifungal and plant disease activities.• TRI24 is the first described gene specific to macrocyclic trichothecene biosynthesis.Graphical abstract

Bacterial co-infection in COVID-19: a call to stay vigilant.

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.

Prevalence of and risk factors for infectious disease syndromic symptoms among pilgrimage to Arba'een mass gathering religious in 2023

BackgroundThere is a growing participation of Shia Muslims, in the Arba'een pilgrimage every year. It is imperative to conduct a comprehensive study on the transmission of diseases among Arba'een pilgrims in order to identify and promptly respond to potential epidemics effectively. We aimed to assess the syndromic symptoms associated with infectious diseases and the prevalence of mask usage among patients visiting outpatient clinics during the Arba'een pilgrimage in Ira, in 2023. MethodsIn this descriptive-analytical study, 300 outpatients who sought medical care at outpatient clinics during the Arba'een pilgrimage were randomly selected. The study data and infectious disease syndromic symptoms were assessed using trained healthcare professionals. A multiple logistic regression analysis was carried out to estimate the crude and Adjusted odds ratios (AORs) of symptoms and risk factors associated with respiratory syndrome and flu-like symptoms with 95 % confidence intervals. ResultsThe mean age of the participants was 39 years and 61 % of those were male. Out of 72 (24 %) of mask users, 41.6 % had changed masks in less than 8 h. The most common syndromic symptoms was Flu-like illness (53 %). In the final analysis, not wearing a mask AOR = 1.40 (1.1–9.8) and smoking AOR = 3.25 (1.1–9.5) both elevated the risk of the flu-like syndrome and severe respiratory disease symptoms. ConclusionsPilgrims are especially vulnerable to the flu and other respiratory illnesses. Therefore, performing a differential diagnosis in these people, including flu and COVID-19, is essential to prevent an outbreak during the Arba'een pilgrimage.

A Randomized Placebo-Controlled Trial of Leronlimab in Mild-To-Moderate COVID-19

PurposeEarly in the course of the SARS-CoV-2 pandemic it was hypothesised that host genetics played a role in the pathophysiology of COVID-19 including a suggestion that the CCR5-Δ32 mutation may be protective in SARS-CoV-2 infection. Leronlimab is an investigational CCR5-specific humanized IgG4 monoclonal antibody currently in development for HIV-1 infection. We aimed to explore the impact of leronlimab on the severity of disease symptoms among participants with mild-to-moderate COVID-19. MethodsThe TEMPEST trial was a randomized, double-blind, placebo-controlled study in participants with mild-to-moderate COVID-19. Participants were randomly assigned in a 2:1 ratio to receive subcutaneous leronlimab (700 mg) or placebo on days 0 and 7. The primary efficacy endpoint was assessed by change in total symptom score based on fever, myalgia, dyspnea, and cough, at end of treatment (day 14). FindingsOverall, 84 participants were randomized and treated with leronlimab (n = 56) or placebo (n = 28). No difference was observed in change in total symptom score (P = 0.8184) or other pre-specified secondary endpoints between treatments. However, in a post hoc analysis, 50.0% of participants treated with leronlimab demonstrated improvements from baseline in National Early Warning Score 2 (NEWS2) at day 14, compared with 20·8% of participants in the placebo group (post hoc; p = 0.0223). Among participants in this trial with mild-to-moderate COVID-19 adverse events rates were numerically but not statistically significantly lower in leronlimab participants (33.9%) compared with placebo participants (50.0%). ImplicationsAt the time the TEMPEST trial was designed although CCR5 was known to be implicated in COVID-19 disease severity the exact pathophysiology of SARS-CoV-2 infection was poorly understood. Today it is well accepted that SARS-CoV-2 infection in asymptomatic-to-mild cases is primarily characterized by viral replication, with a heightened immune response, accompanied by diminished viral replication in moderate-to-severe disease and a peak in inflammatory responses with excessive production of pro-inflammatory cytokines in critical disease. It is therefore perhaps not surprising that no differences between treatments were observed in the primary endpoint or in pre-specified secondary endpoints among participants with mild-to-moderate COVID-19. However, the results of the exploratory post hoc analysis showing that participants in the leronlimab group had greater improvement in NEWS2 assessment compared to placebo provided a suggestion that leronlimab may be associated with a lower likelihood of people with mild-to-moderate COVID-19 progressing to more severe disease and needs to be confirmed in other appropriately designed clinical trials.ClinicalTrials.gov number, NCT04343651 https://classic.clinicaltrials.gov/ct2/show/NCT04343651

Perception of fecal microbiota transplantation in patients with ulcerative colitis in Korea: a KASID multicenter study.

Fecal microbiota transplantation (FMT) is a promising therapy for inducing and maintaining remission in patients with ulcerative colitis (UC). However, FMT has not been approved for UC treatment in Korea. Our study aimed to investigate patient perceptions of FMT under the national medical policy. This was a prospective, multicenter study. Patients with UC ≥ 19 years of age were included. Patients were surveyed using 22 questions on FMT. Changes in perceptions of FMT before and after education were also compared. A total of 210 patients with UC were enrolled. We found that 51.4% of the patients were unaware that FMT was an alternative treatment option for UC. After reading the educational materials on FMT, more patients were willing to undergo this procedure (27.1% vs. 46.7%; p < 0.001). The preferred fecal donor was the one recommended by a physician (41.0%), and the preferred transplantation method was the oral capsule (30.4%). A large proportion of patients (50.0%) reported that the national medical policy influenced their choice of FMT treatment. When patients felt severe disease activity, their willingness to undergo FMT increased (92.3% vs. 43.1%; p = 0.001). Education can increase preference for FMT in patients with UC. When patients have severe disease symptoms or their quality of life decreases their willingness to undergo FMT increases. Moreover, national medical policies may influence patient choices regarding FMT.

Quality of life in SCN1A-related seizure disorders across the lifespan.

This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other SCN1A-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a SCN1A-related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [β = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (β = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (β = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, P < 0.05), mediated by a lower prevalence of behavioural problems (β = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (β = -0.1, 95%CI (-0.2 to -0.0)) and older age (β = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.

Improvement in signs and symptoms of severe dry eye disease after dual therapy with high-potency steroids and 0.05% cyclosporine

Objective To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). Materials and methods This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. Results In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). Conclusions Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.

Risk Factors and Distribution of Infectious Diseases among the Older Adults on a Pilgrimage to Arba’een Mass Gathering

Objectives: To determine the syndromic symptoms associated with infectious diseases in the older adults attending the Arba’een pilgrimage mass gathering. Design: A cross-sectional study. Setting(s): Outpatient clinics during the Arba’een pilgrimage. Participants: A total of 200 subjects were randomly chosen among the older adults attending outpatient clinics during the Arba’een pilgrimage in Iraq in 2022. Outcome measures: The syndromic symptoms of infectious diseases, including acute fever and rash, influenza-like syndrome, severe acute respiratory syndrome (SARS), food poisoning, acute diarrhea, bloody diarrhea, and chronic cough were evaluated using a valid checklist provided by the Center for Disease Control and Prevention (CDC) and the Ministry of Health (Iran). Multiple logistic regression analysis was carried out to estimate the crude and adjusted odds ratios (AORs) with 95% confidence intervals. Results: The mean age of the participants was 68.3 years, with nearly 60% of the participants being men. Among 72 (29.4%) mask users, 71% changed masks in less than 8 hours. The most common syndromic symptom was flu-like illness (42%). In the final analysis, not using a mask (AOR=1.5, 1.1 – 4.7), diabetes (AOR=3.01, 1.4 – 7.7), and smoking (AOR=1.75, 1.02 – 3.8) increased the risk of the flu-like syndrome and severe respiratory disease symptoms. Conclusions: Flu and respiratory illnesses are common among the aging population attending Arba’een mass gatherings. To prevent potential outbreaks, it is necessary to perform a differential diagnosis of respiratory diseases such as influenza and coronavirus disease 2019 (COVID-19).

Association Between Periodontal Diseases and Hypothyroidism: A Case-Control Study.

Periodontal diseases are chronic inflammatory disorders influenced by systemic health of the individual. This study aimed to investigate the association between hypothyroidism and periodontal disease in a cohort of adult Saudi population. This case-control study included 201 adults with hypothyroidism on hormone replacement therapy and 188 healthy controls. The medical files of patients were reviewed to check thyroid stimulation hormone (TSH) and free thyroxine (FT4) levels. Participants completed a questionnaire on demographic and health information, followed by a comprehensive periodontal examination. Pearson chi-square and binary logistic regression analyses determined associations, with a significance set at p ≤0.05. Gingivitis was found in 20.9% of cases and 58% of controls. Periodontitis stages I, II, III and IV were in general higher in cases compared to controls (23.4%, 27.9%, 21.9%, 6% in cases versus 13.8%, 17%, 9.6%, 1.6% in controls, respectively). Mean PPD and CAL values were higher in cases (5.54 ± 2.5 and 3.88 ± 3.1) than in controls (4.03 ± 1.6 and 1.72 ± 2.4). Significant associations between periodontal status and hypothyroidism were found (p < 0.0001). The periodontal status in hypothyroid cases correlated significantly with hormone replacement therapy dose and duration (p < 0.0001). The findings of the current study showed that, in a cohort of adult Saudi subjects, patients with hypothyroidism have higher prevalence and more severe periodontal disease symptoms compared to controls, suggesting significant association.