Lower Disease Severity Research Articles

Evaluation of Stem Rust Disease in Wheat Fields by Drone Hyperspectral Imaging.

Detecting plant disease severity could help growers and researchers study how the disease impacts cereal crops to make timely decisions. Advanced technology is needed to protect cereals that feed the increasing population using fewer chemicals; this may lead to reduced labor usage and cost in the field. Accurate detection of wheat stem rust, an emerging threat to wheat production, could inform growers to make management decisions and assist plant breeders in making line selections. A hyperspectral camera mounted on an unmanned aerial vehicle (UAV) was utilized in this study to evaluate the severity of wheat stem rust disease in a disease trial containing 960 plots. Quadratic discriminant analysis (QDA) and random forest classifier (RFC), decision tree classification, and support vector machine (SVM) were applied to select the wavelengths and spectral vegetation indices (SVIs). The trial plots were divided into four levels based on ground truth disease severities: class 0 (healthy, severity 0), class 1 (mildly diseased, severity 1-15), class 2 (moderately diseased, severity 16-34), and class 3 (severely diseased, highest severity observed). The RFC method achieved the highest overall classification accuracy (85%). For the spectral vegetation indices (SVIs), the highest classification rate was recorded by RFC, and the accuracy was 76%. The Green NDVI (GNDVI), Photochemical Reflectance Index (PRI), Red-Edge Vegetation Stress Index (RVS1), and Chlorophyll Green (Chl green) were selected from 14 SVIs. In addition, binary classification of mildly diseased vs. non-diseased was also conducted using the classifiers and achieved 88% classification accuracy. This highlighted that hyperspectral imaging was sensitive enough to discriminate between low levels of stem rust disease vs. no disease. The results of this study demonstrated that drone hyperspectral imaging can discriminate stem rust disease levels so that breeders can select disease-resistant varieties more efficiently. The detection of low disease severity capability of drone hyperspectral imaging can help farmers identify early disease outbreaks and enable more timely management of their fields. Based on this study, it is also possible to build a new inexpensive multispectral sensor to diagnose wheat stem rust disease accurately.

Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens.

We investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity. We used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and an S- and N-IgG antibody ELISA to screen for SARS-CoV-2-specific cross-reactivity. HCoV-OC43-, HCoV-229E-, and SARS-CoV-2-specific IFN-γ occurred in 23, 15, and 17 of 104 specimens, respectively. Cross-reactive IgG was more common against the nucleoprotein (7/110, 15.5%; p = 0.0016, Fishers' Exact) than the spike (3/110, 2.72%). Specimens lacking anti-HuCoV antibodies had higher rates of pre-epidemic SARS-CoV-2-specific IFN-γ cross-reactivity (p-value = 0.00001, Fishers' exact test), suggesting that exposure to additional factors not examined here might play a role. SARS-CoV-2-specific cross-reactive antibodies were significantly less common in HIV-positive specimens (p=0.017; Fishers' Exact test). Correlations between SARS-CoV-2- and HuCoV-specific IFN-γ responses were consistently weak in both HIV negative and positive specimens. These findings support the existence of pre-epidemic SARS-CoV-2-specific cellular and humoral cross-reactivity in this population. The data do not establish that these virus-specific IFN-γ and antibody responses are entirely specific to SARS-CoV-2. Inability of the antibodies to neutralise SARS-CoV-2 implies that prior exposure did not result in immunity. Correlations between SARS-CoV-2 and HuCoV-specific responses were consistently weak, suggesting that additional variables likely contributed to the pre-epidemic cross-reactivity patterns. The data suggests that surveillance efforts based on the nucleoprotein might overestimate the exposure to SARS-CoV-2 compared to inclusion of additional targets, like the spike protein. This study, while limited in scope, suggests that HIV-positive people are less likely than HIV-negative people to produce protective antibodies against SARS-CoV-2.

Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain)

ABSTRACT The emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher’s exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p = 2.89 × 10−25; vs. BA.1 p = 5.17 × 10−11; vs. BA.2 p = 0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] = 0.45, 95% Confidence Interval [CI] = 0.23-0.87, p = 0.02), BA.2 (OR = 0.38, 95% CI = 0.22-0.63, p = 1.91 × 10−4), and BA.5 (OR = 0.30, 95% CI = 0.16-0.55, p = 1.05 × 10−4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern.

Estrogen ameliorates sepsis-induced vascular hyporeactivity in thoracic aorta of female rats via permissive effect of GRα expression

ObjectiveEstrogen is correlated to the lower mortality and disease severity of female than that of male, which indicates the potential therapeutic role of estrogen supplement therapy in sepsis. The structure of Daidzein is similar to that of 17β estradiol (E2), an estrogen in human body, causing the exogenous Daidzein can interact with estrogen receptor as well as E2 in the body. We aim to explore the therapeutic role of estrogen in sepsis-induced vascular dysfunction. Also, we wonder if estrogen regulates blood pressure via glucocorticoid-mediated vascular reactivity. MethodsFemale SD rats received ovariectomy (OVX) to induce estrogen deficiency. After 12 weeks of administration, cecal ligation and puncture (CLP) was used to establish the in vivo model of sepsis. Lipopolysaccharide (LPS) was used to construct the in vitro model of sepsis in vascular smooth muscle cells (VSMCs). E2 and Daidzein were used for estrogen supplement therapy. ResultsE2 and Daidzein significantly inhibited inflammation infiltration and histopathological injury in thoracic aorta in the rat model with CLP. E2 and Daidzein improved carotid pressure and vascular hyporeactivity in sepsis rats with OVX. Importantly, E2 and Daidzein promoted glucocorticoid permissive action and increased glucocorticoid receptor α (GRα) expression in thoracic aorta smooth muscle cells. E2 and Daidzein upregulated GRα, and inhibits cytokine production, proliferative phenotype and cell migration in LPS-induced VSMCs. ConclusionEstrogen improved vascular hyporeactivity in thoracic aorta induced by sepsis via permissive effect of GRα expression.

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome.

The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70-80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, "Why this variation?" remains largely unanswered.

A54 THE IMPACT OF NON-INVASIVE TRANSCUTANEOUS AURICULAR VAGUS NERVE STIMULATION (NITAVNS) ON THE DEVELOPMENT OF EXPERIMENTAL COLITIS IN MICE

Abstract Background The anti-inflammatory impacts of stimulating the vagus nerve as a part of the gut-brain axis on intestinal macrophage activity and inflammatory cytokine production have been documented. While vagus nerve stimulation until now has been chiefly invasive, non-invasive auricular vagus nerve stimulation (NitaVNS) has no adverse effects associated with invasive stimulation. The NitaVNS-mediated activation of brainstem nuclei can exert anti-inflammatory effects directly on the colon or indirectly through the spleen via a macrophage-acetylcholine-dependent pathway. Purpose To examine the effects of NitaVNS on the development of acute colitis in mice using a preclinical model. Method Thirty C57BL/6 mice aged 11 to 12 weeks were divided into four groups: control (CTRL)-NitaVNS, CTRL-Sham, dextran sulphate sodium (DSS)-NitaVNS and DSS-Sham. Pre-set stimulation parameters (10 minutes duration, 10 V voltage, 500 s pulse width, and 20 Hz frequency) were applied for NitaVNS or sham-paw stimulation. 5% DSS was administered to induce colitis for five consecutive days, whereas CTRL mice received regular water. Weight loss, stool consistency, blood in the feces, and disease activity index were evaluated daily. Rectal bleeding, colon bleeding, and fecal consistency were determined as a composite macroscopic score upon sacrifice. Collected colon and blood samples were assessed for pro-inflammatory parameters such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, C-reactive protein (CRP), matrix metalloproteinase (MMP)-2, macrophage inflammatory protein (Mip)-1α and β, and anti-inflammatory cytokine tumor growth factor (TGF)-β using qRT-PCR and ELISA. Result(s) Compared to colitic-sham mice, colitic NitaVNS mice demonstrated a delayed onset and a significantly lower clinical disease severity. Colitis induced significant weight loss, rectal bleeding, and stool consistency loss, and NitaVNS significantly abolished these effects. In colitic conditions, NitaVNS decreased the disease activity index significantly compared to the colitic sham group. Colitis increased the macroscopic scores, and NitaVNS decreased them significantly. Conversely, colon length was significantly reduced in colitic conditions, but NitaVNS abrogated that deleterious effect. mRNA expression levels of IL-1β and TNF-α were significantly increased in colitic mice and NitaVNS decreased them significantly. Whereas Mip-1α and 1β were not modified in colitic conditions, NitaVNS significantly decreased these markers. MMP2 mRNA expression and colonic IL-6 and IL-1β protein levels were not altered in all conditions. However, colitis induced a significant decrease in colonic TGF-β levels, but NitaVNS did not amplify that effect. Interestingly, in the serum of colitic mice, NitaVNS significantly increased and decreased TGF-β and CRP levels, respectively. Conclusion(s) These findings suggest that NitaVNS possess some spatial anti-inflammatory effects in acute colitis through the up or downregulation of anti- or pro-inflammatory markers. Disclosure of Interest F. Hesampour: None Declared, D. Tshikudi: None Declared, A. Veysel Özden Employee of: Company providing the stimulator, C. N. Bernstein: None Declared, J.-E. Ghia: None Declared

Genotype-Phenotype Associations of Children With Familial Mediterranean Fever in a Cohort Consisting of M694V Mutation and Implications for Colchicine-Resistant Disease.

The aim of this study was to investigate the clinical associations of the second allele mutations and the effect of genotype and presenting features on colchicine resistance in children with familial Mediterranean fever (FMF), carrying at least one M694V variant. The medical records of the patients diagnosed with FMF, in whom at least one allele M694V mutation was detected, were reviewed. Patients were grouped according to the genotype as M694V homozygotes, compound heterozygote M694V with an exon 10 mutation, compound heterozygote M694V with a variant of unknown significance (VUS), and M694V heterozygotes. Disease severity was assessed with the International Severity Scoring System for FMF. Among the 141 patients included, homozygote M694V (43.3%) was the most frequent MEFV genotype. Clinical manifestations of FMF at diagnosis were not significantly different according to genotypic alterations except homozygote M694V. Besides, homozygous M694V was associated with a more severe disease, with more frequent comorbidities and colchicine-resistant disease. A lower disease severity score was observed in compound heterozygotes with VUS than in M694V heterozygotes (median 1 vs 2, p = 0.006). Regression analysis revealed that homozygous M694V, arthritis, and frequency of attacks were associated with an increased risk of colchicine-resistant disease. Clinical manifestations of FMF at diagnosis with a M694V allele were predominantly influenced by the M694V rather than the second allele mutations. Although homozygous M694V was associated with the most severe form, the presence of compound heterozygosity with a VUS did not affect disease severity or clinical features. Homozygous M694V confers the highest risk of colchicine-resistant disease.

Determination of the severity of soft rot and blackleg caused by Pectobacterium brasiliense in some potato genotypes from Turkey

Pectobacterium species are one of the main bacterial agents of soft rot and blackleg diseases that cause economic damage to potato crops. Farmers around the world suffer losses from both diseases and use different strategies to control. In this study, local potato genotypes were evaluated for disease severity of soft rot and blackleg. We discovered putative genotypes with low disease severity for both diseases. In the tuber experiment, the lowest soft rot was determined for genotype 18 with 34% disease severity. The highest soft rot was found in the cultivars Natasha, Laperla and Sultanecem. In the plant experiment, the lowest lesion length was measured in the cultivars Sultannur, Orchestra and Marabel. The 33% disease severity for these cultivars was also calculated for genotypes 18 and 32. With regard to soft rot and blackleg of potato, this is the first study to determine disease severity of Turkish local potato genotypes.

Influence of Physical Attractiveness and Gender on Patient Preferences in Digital Doctor Consultations: Experimental Study.

The rise of digital health services, particularly digital doctor consultations, has created a new paradigm in health care choice. While patients traditionally rely on digital reviews or referrals to select health care providers, the digital context often lacks such information, leading to reliance on visual cues such as profile pictures. Previous research has explored the impact of physical attractiveness in general service settings but is scant in the context of digital health care. This study aims to fill the research gap by investigating how a health care provider's physical attractiveness influences patient preferences in a digital consultation setting. We also examine the moderating effects of disease severity and the availability of information on health care providers' qualifications. The study uses signal theory and the sexual attribution bias framework to understand these dynamics. Three experimental studies were conducted to examine the influence of health care providers' physical attractiveness and gender on patient preferences in digital consultations. Study 1 (n=282) used a 2×2 between-subjects factorial design, manipulating doctor attractiveness and gender. Study 2 (n=158) focused on women doctors and manipulated disease severity and participant gender. Study 3 (n=150) replicated study 2 but added information about the providers' abilities. This research found that patients tend to choose attractive doctors of the opposite gender but are less likely to choose attractive doctors of the same gender. In addition, our studies revealed that such an effect is more prominent when the disease severity is high. Furthermore, the influence of gender stereotypes is mitigated in both the high and low disease severity conditions when service providers' qualification information is present. This research contributes to the literature on medical information systems research and sheds light on what information should be displayed on digital doctor consultation platforms. To counteract stereotype-based attractiveness biases, health care platforms should consider providing comprehensive qualification information alongside profile pictures.

Occurrence Rate and Outcomes of Weaning Groups According to a Refined Weaning Classification: A Retrospective Observational Study.

The weaning according to a new definition (WIND) classification groups mechanically ventilated (MV) patients into "short weaning," "difficult weaning," "prolonged weaning," and "no weaning." The aims of the study were: 1) to describe the weaning group distribution, 2) to evaluate if "short weaning" patients can be divided into groups with distinct characteristics and outcomes depending on the MV duration, and 3) to study 1-year outcomes related to weaning groups. Retrospective observational study. Tertiary center with a mixed, mainly surgical ICU population. MV patients admitted between April 11, 2018, and April 10, 2019. None. A refined WIND classification was used, dividing "short weaning" patients into patients MV less than or equal to 24 hours, "short weaning a," and those MV greater than 24 hours, "short weaning b." Data were collected from electronic medical records. Of 1,801 MV patients, 65% were categorized as "short weaning a," 13% "short weaning b," 8% "difficult weaning," 6% "prolonged weaning," and 8% "no weaning." "Short weaning a" patients were older, more frequently male, and had lower disease severity compared with "short weaning b." Weaning duration (days: 0 [0-0] to 14 [10-21]), weaning success rate (99-69%), ICU length of stay (days: 2 [1-4] to 28 [19-48]), ICU mortality (1-37%), and hospital length of stay (days: 10 [7-18] to 48 [27-89]) and hospital mortality (4-42%; all p < 0.01) increasingly worsened from "short weaning a" to "prolonged weaning." One-year mortality increased from "short weaning a" (9%) to "short weaning b" (27%), "difficult weaning" (39%), and "prolonged weaning" (49%). In adjusted analyses, weaning groups remained independently associated with 1-year mortality. The high proportion of "short weaning" patients in this mainly surgical ICU population could be divided into two groups with distinct characteristics. This refined WIND classification allowed to enhance prognostication, also beyond hospitalization, highlighting the need to further optimize the weaning process.

Interstitial Lung Disease in Primary Biliary Cholangitis: A Cohort Prospective Study.

Interstitial lung disease (ILD) has been recognized as an extrahepatic manifestation ofprimary biliary cholangitis (PBC), althoughlimited data are available on its prevalence and clinical significance. Therefore, we evaluated the occurrence and clinical features of ILD in a cohort of PBC patients. Ninety-three individuals without concomitant rheumatic diseases were enrolled in our prospective cohort study. All patients underwent chest high-resolution computed tomography (HRCT). Liver-related and lung-related survival wereassessed. A lung-related outcome was defined as death from ILD complications; a liver-related outcome was defined as liver transplantation or death from liver cirrhosis complications. HRCT findings suggestive ofILD were detected in 38 patients (40.9%). A sarcoid-like pattern of PBC-associated ILD was the most frequent, followed by subclinical ILD and organizing pneumonia. Patients with ILD were less likely to have liver cirrhosis and liver-related symptoms and presented with higher serum immunoglobulin M(IgM) and M2 subtype antimitochondrial antibodies (AMA-M2) positivity rates. In a multivariate analysis, the absence of liver disease symptoms at the disease presentation (OR 11.509; 95% CI 1.210-109.421; p = 0.033), the presence of hepatic non-necrotizing epithelioid cell granulomas (OR 17.754; 95% CI 1.805-174.631; p = 0.014), higher serum IgM (OR 1.535; 95% CI 1.067-2.208; p = 0.020) and higher blood leukocyte count (OR 2.356; 95% CI 1.170-4.747; p = 0.016) were independent risk factors associated with ILD in PBC. More than a third of patients with ILD showed no respiratory symptoms, and only one ILD-related death occurred during a follow-up of 29.0 months (IQR 11.5; 38.0). Patients with ILD had better liver transplant-free survival.ILD in PBC had a benign course and was associated with a lower liver disease severity. PBC-associated ILD should be included in a list of differential diagnoses of ILD.

Diphenylcyclopropenone Treatment Outcomes for Alopecia Areata

Objective: To ascertain (1) Diphenylcyclopropenone (DCP)’s efficacy in treating alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in Thai patients; and (2) prognostic factors. Materials &amp; Methods: We retrospectively reviewed the medical records of patients with AA, AT, and AU who were administered DCP at Siriraj Hospital, Bangkok, Thailand. The median response and relapse times of the 3 groups were evaluated. Factors affecting outcomes were investigated. Results: Fifty-nine cases were enrolled (AA, 22; AT, 9; AU, 28), with women predominating in each group. The overall response was 61% (AA, 78.6%; AT, 66.7%; AU, 50%). The median response time was 58 weeks, with a significantly longer time for AU than AA (P = 0.006). Factors significantly influencing response to DCP, evaluated by multivariate analysis, were older age at onset (P = 0.02), disease duration before DCP initiation (P = 0.003), and treatment duration to initial hair regrowth (P = 0.001). The overall relapse rate was 63.9%, with a median of 39 weeks between response and relapse. The most common side effect was blistering (73.7%). Conclusion: DCP is effective and safe for treating extensive AA. Favorable prognostic factors are low disease severity, late disease onset, short duration before DCP treatment, and short duration to initial response. As the relapse rate is high, maintenance therapy should be considered.

P879 Clinical significance of plasma interleukin-22 as a biomarker of inflammation in patients with Crohn’s disease and ulcerative colitis

Abstract Background IL-22 is a key cytokine in the pathogenesis of inflammatory bowel disease (IBD). While evidence underpinning its central role as a biomarker of pathway activation, diagnosis, severity and activity for IBD has been accumulating, little is known about its application as a biomarker in IBD in real-world practice. Here, we characterize for the first time the relationship between IL-22 plasma concentrations and the clinical characteristics of a large, real-world population of patients with IBD. Methods This is a descriptive analysis of patients in the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus registry of the Crohn’s &amp; Colitis Foundation in the United States. The SPARC registry includes patients with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). This study evaluated baseline data collected within ± 30 days from consent date. Assessments included demographics, clinical characteristics and IL-22 plasma concentrations. Disease severity was assessed using short CD Activity Index (sCDAI; scores &amp;lt;150 define remission, 150–219 mild activity, ≥220 moderate-severe activity) or 6-point UC Disease Activity Index (UCDAI; scores ≤1 define remission, 2–3 mild activity, ≥4 moderate-severe activity) disease severity categories. Results A total of 2667 patients with CD and 1326 patients with UC were eligible for inclusion in the study. For patients with CD, median age was 39 years, 57% were female and median disease duration was 13 years (Table 1). For patients with UC, median age was 40 years, 51% were female and median disease duration was 9 years (Table 1). In total, 1604 patients with CD and 836 patients with UC had valid IL-22 samples at baseline, of which 33% and 25%, respectively, were above the lower limit of quantification (LLOQ; 7.8 pg/mL). There was a trend toward fewer patients with IL-22 levels below the LLOQ among patients with high disease severity compared with those with lower disease severity both in patients with CD and those with UC (Figure 1). Additionally, there was an increase in the percentage of patients with IL-22 levels greater than the third quartile (overall Q3 = 10.8 pg/mL in CD, and = 7.9 pg/mL in UC) with increased disease severity (Figure 2). Comparison of subgroups of patients with low and medium/high IL-22 levels showed a consistent pattern with fewer patients in remission and more moderate-severe patients in the medium/high IL-22 group than in the low IL-22 group (Table 2). Conclusion Higher IL-22 levels tended to be associated with higher disease activity in this real-world population of IBD patients.

High titers of neutralizing SARS-CoV-2 antibodies six months after symptom onset are associated with increased severity in COVID-19 hospitalized patients

BackgroundViral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020–2021.Materials and methodsProspective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 – 10), 37 (IQR 35 – 38), 97 (IQR 95 – 100), and 187 (IQR 185 – 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells.ResultsPatients with high disease severity had higher mean log2 NAb titers at day 37 (1.58, 95% CI [0.34 –2.81]), 97 (2.07, 95% CI [0.53–3.62]) and 187 (2.49, 95% CI [0.20– 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [− 0.627 – 0.728]), expressed as log10 SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission.ConclusionsWe document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity.Trial registration. The study is registered at https://clinicaltrials.gov/ (NCT05274373).

Involvement of salicylic acid against anthracnose disease in cassava

In this research, the involvement of salicylic acid (SA) as a plant growth regulator and a disease protector was investigated. SA at 9 concentrations was tested for their phytotoxicity, then 4 concentrations were selected for evaluating the effect of SA on root quantity and length as well as to study its inhibitory efficacy on mycelial growth and spore germination of Colletotrichum gloeosporioides, cassava anthracnose. The results showed that four low concentrations from 50–500 mg L−1 had no burns on leaf tissues. The SA at concentrations of 200 mg L−1 had high root number and length as well as effectively inhibited mycelial growth and spore germination of Colletotrichum. Subsequently, SA at 200 mg L−1 was tested under field conditions for two crop seasons. The plant height of SA treated-cassava was 178.36 ± 9.65 cm in the first crop season, and the height in the second crop season at 151.41 ± 5.55 cm, all effective when compared to the water control. For the anthracnose severity assessment, at 9 months old, plants treated with SA had lower disease severity.

Access of Syrian refugees to COVID-19 testing in Lebanon.

Polymerase chain reaction is a well-known method for testing COVID-19 infection, however, refugee populations often face difficulties in accessing testing. Several structural and cultural challenges have hindered access of Syrian refugees to COVID-19 testing in Lebanon, including financial barriers, stigma, and low perception of vulnerability. To explore barriers to accessing COVID-19 testing by Syrian refugees in Lebanon. This qualitative study conducted 10 focus group discussions among Syrian refugees and 21 individual semistructured interviews with healthcare workers. Ethical approval was obtained from the Institutional Review Board of the Lebanese International University, and the study followed the ethical principles of the Declaration of Helsinki. Syrian refugees in Lebanon did not consider COVID-19 testing to be important. Despite the availability of free testing services, psychological, cultural, environmental, and financial barriers hindered them from getting tested. Some of them relied on consultation with pharmacists, who were easy to access and provided symptomatic treatment without the need to test for COVID-19. Fear of stigma, deportation, and isolation were common cultural barriers. Testing was considered unnecessary because of the perception of low disease severity and an attitude of negligence towards preventive practices. The harsh economic and living conditions were of greater concern to the refugees. Findings from this study add to existing literature regarding the social and cultural barriers to COVID-19 testing among Syrian refugees and should be considered when tailoring health promotion campaigns to halt the spread of the COVID-19 pandemic.

Oral diseases in 12-year-old schoolchildren in a capital city in northeast Brazil: rise or decline?

This cross-sectional study aimed to analyze the distribution of oral diseases in 12-year-old schoolchildren in Fortaleza, Northeast, Brazil. Based on the SB Brasil 2010, 30 calibrated dentists evaluated 1,509 children. Data were submitted to Pearson's Chi-square or Fisher's Exact tests, considering p&lt;0.05. It was observed that 67.3% of the children were caries free and the mean DMFT-D was 0.86, with a predominance of the carious component (69.8%) in its composition. Main needs found: restorations (33.5%), pulp treatment (4.8%) and extractions (4.1%). The prevalence of fluorosis was 32.5%. As for periodontal disease, 56.6% of the students did not present bleeding and the presence of calculus in the examined sextants. The prevalence of malocclusion was 40.3%. It is concluded that the Municipality of Fortaleza has low caries severity and low prevalence of periodontal disease. Fluorosis is more prevalent in the very mild form. The total number of children with normal occlusion was greater than those with malocclusion. Regarding the severity of malocclusion detected, defined malocclusion prevailed. A decline in caries disease was observed, however, fluorosis and malocclusion showed an increase when compared to previous epidemiological surveys.

Potential use of Terasi, an Indonesian traditional fermented seafood paste, to provide healthy lettuce (Lactuca sativa L.) seedling

Terasi paste consists of plant nutrients and microorganisms that potentially improve the health of plant seedlings. We evaluated the effects of terasi paste on seed germination, seedling growth, and root rot disease severity caused by Fusarium oxysporum f.sp. lactucae (FOL) in lettuce. Terasi paste was tested at four different weights (i.e., 0.00 g [T0], 1.00 g [T1], 2.50 g [T2], and 5.00 g [T3]) in the 100 g nursery soil. The results showed that lettuce seeds from T1 and T2 treatments were fully germinated, as observed for the T0 treatment. However, 40.0% of lettuce seeds from T3 treatment failed to germinate. Thus, 1.00 g and 2.50 g terasi applications in the 100 g soil did not affect lettuce seed germination. Moreover, T1 and T2 treatments tended to improve the shoot and root biomass of lettuce seedlings over T0 treatment, while T3 treatment showed the opposite effects. Following FOL infection, the lettuce seedlings from T2 and T3 treatments had 31.1% significantly lower disease severity than those from the T0 treatment. Therefore, T2 treatment (i.e., 2.50 g terasi application in the 100 g soil) imparts maximum health-promoting benefits to lettuce seedlings.

Deletion induced splicing in RIC3 drives nicotinic acetylcholine receptor regulation with implications for endoplasmic reticulum stress in human astrocytes.

Nicotinic acetylcholine receptor (nAChR) dysregulation in astrocytes is reported in neurodegenerative disorders. Modulation of nAChRs through agonists confers protection to astrocytes from stress but regulation of chaperones involved in proteostasis with pathological implications is unclear. Resistance to inhibitors of cholinesterase 3 (RIC3), a potential chaperone of nAChRs is poorly studied in humans. We characterized RIC3 in astrocytes derived from an isogenic wild-type and Cas9 edited "del" human iPSC line harboring a 25 bp homozygous deletion in exon2. Altered RIC3 transcript ratio due to deletion induced splicing and an unexpected gain of α7nAChR expression were observed in "del" astrocytes. Transcriptome analysis showed higher expression of neurotransmitter/G-protein coupled receptors mediated by cAMP and calcium/calmodulin-dependent kinase signaling with increased cytokines/glutamate secretion. Functional implications examined using tunicamycin induced ER stress in wild-type astrocyte stress model showed cell cycle arrest, RIC3 upregulation, reduction in α7nAChR membrane levels but increased α4nAChR membrane expression. Conversely, tunicamycin-treated "del" astrocytes showed a comparatively higher α4nAChR membrane expression and upsurged cAMP signaling. Furthermore, reduced expression of stress markers CHOP, phospho-PERK and lowered XBP1 splicing in western blot and qPCR, validated by proteome-based pathway analysis indicated lowered disease severity. Findings indicate (i) a complex RNA regulatory mechanism via exonic deletion induced splicing; (ii) RIC-3 as a disordered protein having contrasting effects on co-expressed nAChR subtypes under basal/stress conditions; and (iii) RIC3 as a potential drug target against ER stress in astrocytes for neurodegenerative/nicotine-related brain disorders. Cellular rescue mechanism through deletion induced exon skipping may encourage ASO-based therapies for tauopathies.

Anosmia in COVID-19 Patients: Can We Predict the Severity of Chest Manifestations?

Introduction Anosmia is one of the common symptoms of COVID-19, the link between severity of chest infection and anosmia was investigated by few studies. Objectives To find an association between anosmia and severity of chest infection. Methods An analysis of patients admitted to isolation hospital of our university with confirmed polymerase chain reaction positive testing for COVID-19, between March 2021 until September 2021. We called all patients who reported anosmia during their time of illness and asked them about anosmia. We examined their chest CT. A statistical analysis was done. Results A total of 140 patients completed the study; 65% were female and 56.4% had complete anosmia. Anosmia was significantly associated with loss of taste. Smell returned in 92.5% of anosmic patients. Duration of smell loss was ∼ 2 weeks in 40.5%. The most common symptoms associated with anosmia were running nose, sore throat, fever, and cough. Loss of smell was significantly associated with mild chest disease. 73.4% of anosmic patients had mild chest infection, 21.5% of them had moderate infection, and 5.1% had severe chest infection. Conclusion The pattern of anosmia in COVID-19 patients has some common similarities in general; the way it starts, the associated symptoms, the time until smell returns and, the most important, the severity of chest infection. As anosmia is significantly associated with mild chest infection. the presence of anosmia could be an independent predictor of good COVID-19 outcome as reflected by a lower disease severity and less frequent ICU admissions.