Severe Reduction Research Articles

Macular vascular density alteration patterns in paediatric optic neuritis patients with serum MOG antibody positivity detected by optic coherence tomography angiography

PurposeThe retinal microvascular network plays a crucial role in inflammatory injury in paediatric optic neuritis (PON) with serum MOG antibody positivity (MOG + PON). This study compared retinal microvascular densities and structural alterations in MOG + PON eyes with paediatric isolated optic neuritis (PION) eyes and followed up with the final best-corrected visual acuity (BCVA) after 6 months. MethodsA total of 29 children (52 eyes) with PON, including 15 MOG + PON cases (28 eyes), 6 PION cases (10 eyes), 2 neuromyelitis optica spectrum disorders associated PON(NMOSD-PON) cases (4 eyes), 6 MOG-associated disease (MOGAD) patients without ON-affected eyes (MOG + NPON) cases (10 eyes) and age- and gender-matched healthy controls (HCs) underwent superficial/deep retinal angiography density (SAD/DAD) by optical coherence tomography angiography (OCTA). Their BCVAs were followed up until 6 months after PON onsets. ResultsMOG + PON cases had better final BCVAs than PION and NMOSD-ON. MOG + PON (35.7 ± 10.3 %) and PION (40.1 ± 10.3 %) eyes experienced severe SAD reductions in contrast to MOGAD+NPON (48.7 ± 5.2 %) and HCs eyes (55.6 ± 8.2 %). However, DAD in MOG + PON eyes (48.5 ± 9.2 %) and MOG + NPON eyes (53.1 ± 3.3 %) increased compared to HC eyes (45.7 ± 9.6 %; p = 0.028 and 0.009, respectively). SAD reduction occurred in acute PON and was detected as early as 2 weeks after PON onset. ConclusionsMOG + PON eyes had better final BCVAs than PION eyes, which displayed superficial retinal microvascular perfusion reductions and deep microvascular perfusion increases. SAD could be a sensitive surrogate for PON attacks in children with MOGAD.

Combination of trehalose and botulinum toxin type A in REVITOX skin treatment protocols

This article presents the REVITOX protocol, developed by the author, which includes the combination of REVI products (native hyaluronic acid + trehalose) and botulinum toxin type A (BTA) for the treatment of rosacea and correction of age-related changes. A plethora of studies has demonstrated that trehalose, an exceptional stabilizer of proteins, contributes to maintaining cellular integrity, exhibits antioxidant and angioprotective effects, and has been shown to induce autophagy. In combination with the proven effects of hyaluronic acid and BTA, these properties facilitate the optimal environment for cellular structure functioning, influencing the basic mechanisms of rosacea pathogenesis and mitigating the severity of age-related changes through the balanced elimination of dynamic and static rhytides, stimulation of neocollagenesis and improvement of the mechanical properties of the dermis. By targeting the multifactorial processes of facial aging, improving skin hydration and elasticity, the REVITOX Beauty protocol has ensured the balanced rejuvenation of the perioral and periorbital skin, resulting in a significant improvement in skin quality, as confirmed by the results of 3D diagnostics. After 3 treatment sessions of the REVITOX Derma program, the patients showed a general improvement of facial skin, a visible reduction in erythema and telangiectasia severity, regression of papulopustular elements, enhanced skin hydration and elasticity, and no recurrences at the follow-up. Further studies on the combined use of BTA and REVI will investigate the potential for using these protocols in the treatment of other dermatological conditions, including in combination with energy-based devices and beauty injections.

Microbiome- and Host Inflammasome-Targeting Inhibitor Nanoligomers Are Therapeutic in the Murine Colitis Model.

Autoimmune and autoinflammatory diseases account for more than 80 chronic conditions affecting more than 24 million people in the US. Among these autoinflammatory diseases, noninfectious chronic inflammation of the gastrointestinal (GI) tract causes inflammatory bowel diseases (IBDs), primarily Crohn's and ulcerative colitis (UC). IBD is a complex disease, and one hypothesis is that these are either caused or worsened by compounds produced by bacteria in the gut. While traditional approaches have focused on pan immunosuppressive techniques (e.g., steroids), low remission rates, prolonged illnesses, and an increased frequency of surgical procedures have prompted the search for more targeted and precision therapeutic approaches. IBD is a complex disease resulting from both genetic and environmental factors, but several recent studies have highlighted the potential pivotal contribution of gut microbiota dysbiosis. Gut microbiota are known to modulate the immune status of the gut by producing metabolites that are encoded in biosynthetic gene clusters (BGCs) of the bacterial genome. Here, we show a targeted and high-throughput screening of more than 90 biosynthetic genes in 41 gut anaerobes, through downselection using available bioinformatics tools, targeted gene manipulation in these genetically intractable organisms using the Nanoligomer platform, and identification and synthesis of top microbiome targets as a Nanoligomer BGC cocktail (SB_BGC_CK1, abbreviated as CK1) as a feasible precision therapeutic approach. Further, we used a host-directed immune target screening to identify the NF-κB and NLRP3 cocktail SB_NI_112 (or NI112 for short) as a targeted inflammasome inhibitor. We used these top two microbe- and host-targeted Nanoligomer cocktails in acute and chronic dextran sulfate sodium (DSS) mouse colitis and in TNFΔARE/+ transgenic mice that develop spontaneous Crohn's like ileitis. The mouse microbiome was humanized to replicate that in human IBD through antibiotic treatment, followed by mixed fecal gavage from 10 human donors and spiked with IBD-inducing microbial species. Following colonization, colitis was induced in mice using 1 week of 3% DSS (acute) or 6 weeks of 3 rounds of 2.5% DSS induction for a week followed by 1 week of no DSS (chronic colitis model). Both Nanoligomer cocktails (CK1 and NI112) showed a strong reduction in disease severity, significant improvement in disease histopathology, and profound downregulation of disease biomarkers in colon tissue, as assessed by multiplexed ELISA. Further, we used two different formulations of intraperitoneal injections (IP) and Nanoligomer pills in the chronic DSS colitis model. Although both formulations were highly effective, the oral pill formulation demonstrated a greater reduction in biochemical markers compared to IP. A similar therapeutic effect was observed in the TNFΔARE/+ model. Overall, these results point to the potential for further development and testing of this inflammasome-targeting host-directed therapy (NI112) and more personalized microbiome cocktails (CK1) for patients with recalcitrant IBD.

The Link between Endogenous Pain Modulation Changes and Clinical Improvement in Fibromyalgia Syndrome: A Meta-Regression Analysis.

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients.

Treatment of Neuropsychiatric Symptoms in Alzheimer’s Disease with a Cannabis-Based Magistral Formulation: An Open-Label Prospective Cohort Study

Plain Language SummaryThere is a need for an alternative treatment to significantly improve NPS in AD and decrease the caregiver’s stress as well as the financial burden resulting from polypharmacy and institutionalization. Any promising treatment should be safe and reduce the risk of adverse effects. This study evaluated the efficacy of a CBD-rich oil in treating NPS in a cohort of 59 patients with AD over a follow-up of more than 1 year, with a specific focus on its impact on caregiver burden. The study showed a significant reduction in the NPI-Q severity and caregiver’s distress scores after 3 months of intervention, and sustained for up to 24 months of follow-up. Notably, the effectiveness was independent of age, sex, years with AD, type of acetylcholinesterase inhibitors, and NPI-Q severity score before CBD treatment. A low CBD dose and a slow dose titration improve tolerance. These results may indicate that alleviating NPS in people with AD facilitates daily caregiving and improves caregivers’ emotional and physical distress.

Jiawei Xionggui Decoction promotes meningeal lymphatic vessels clearance of β-amyloid by inhibiting arachidonic acid pathway

BackgroundAlzheimer's disease (AD) is an aging-associated form of dementia characterized by the pathological deposition of toxic misfolded proteins in the central nervous system (CNS), which is closely related to the clearance impairment of meningeal lymphatic vessels (mLVs). Thus, enhancement dural meningeal lymphatic drainage to remove amyloid-β (Aβ) is usually considered as a potential therapeutic target for AD. PurposeThis study aimed to investigate the mechanisms of Jiawei Xionggui Decoction (JWXG) to attenuate cognitive dificits in APP/PS1 mice with impaired meningeal lymphatic drainage. MethodsLigation of deep cervical lymph nodes (dcLNs) was performed to establish the mice model of the impaired meningeal lymphatic drainage in APP/PS1 mice. Cognitve behaviors and pathological morphology of mice were assessed. Cerebral blood flow (CBF) of mice was determined using Laser speckle contrast imaging analysis. Serum non-targeted metabolomics analysis was applied to decipher the mechanisms of JWXG in rescuing the impairment of mLVs, and C8-D1A cells were employed to validate in vitro. ResultsDisruption of mLVs in APP/PS1 mice deteriorated cognitive dysfunction, accelerated Aβ burden and glia activation, accompanied by more severe neuropathological damage, CBF reduction and neuroinflammation exacerbation. Serum non-targeted metabolomics analysis indicates the increase of arachidonic acid (AA) metabolic pathway was the key contributor to the neuropathological exacerbation of dcLNs ligation APP/PS1 mice. Interestingly, clinically equivalent dose of JWXG was sufficient to restore mLVs drainage and rescue cognitive performance by inhibiting neuroinflammation depended by AA metabolic pathway in dcLNs ligation APP/PS1 mice. ConclusionOur findings establish a novel mechanism that rescue mLVs by inhibiting AA metabolic pathway to clear brain Aβ, and support JWXG as a feasible treatment strategy for AD by suppressing AA metabolic pathway to improve mLVs drainage efficiency.

The association between slow-wave sleep and choroid plexus calcifications in older adults. Results from the sleep disorders substudy of the Atahualpa Project cohort.

ObjectiveIt has been suggested that choroid plexus calcifications (CPC) may be associated with glymphatic system dysfunction and with disturbed slow-wave (N3) sleep. If this is the case, volumetric analysis of CPC could be used to estimate the functional ability of the glymphatic system. However, data on this association is limited. This study aims to assess the association between percentages of N3 sleep – used as a putative marker of glymphatic system activity – and the volume of CPC in older adults. Patients and methodsCommunity-dwelling individuals aged ≥60 years enrolled in the Atahualpa Project Cohort received head CTs (for automated determinations of CPC volume) and a single-night polysomnography (PSG) for quantification of N3 sleep percentages. Multivariate linear regression and non-parametric models were fitted to assess the association between these variables. ResultsA total of 125 older adults (median age: 65 years; 32 % males) were included. The mean percentage of N3 sleep was 12.4±9.1 %, and the mean volume of CPC was 655±345.3 µL. Non-parametric locally weighted scatterplot smoothing showed that the volume of CPC increased as the percentage of N3 sleep increased, but only when N3 sleep is reduced (up to 12 % of total sleep time). The significance disappeared when PSG parameters were included in the model as well as in participants with normal N3 sleep percentages. ConclusionsStudy results suggest that in the presence of severe reductions in N3 sleep, increased CPC volume may be a manifestation of choroid plexus compensation or adaptation, and not necessarily dysfunction.

Oral inoculation of Fusobacterium nucleatum exacerbates ulcerative colitis via the secretion of virulence adhesin FadA

ABSTRACT Fusobacterium nucleatum (F. nucleatum), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of F. nucleatum are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral F. nucleatum in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of F. nucleatum strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with F. nucleatum facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen F. nucleatum and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.

Social‐ecological systems modeling for drought‐food security nexus

AbstractDroughts pose severe threats to social systems, particularly to food security which is one of the priority targets in the UN's sustainable development goals (SDG 2). The drought‐food insecurity nexus entails the complex social‐ecological systems (SES) relationships (e.g., feedback) that underpin food insecurity, leading to disastrous consequence to society. To advance the knowledge on capturing the SES relationships of the drought‐food insecurity nexus, an SES model was employed (first attempt) to simulate these relationships to inform policies on food security in the context of climate change in Bangladesh. Different “what if” scenarios were examined determining the possible future trajectories of the system under socio‐economic and climate scenarios. Findings revealed that (i) with business‐as‐usual scenario, crop production and food security continue to increase at the expense of declining water resources over the simulation period; (ii) temperature changes (3.5–5.7°C) and surface water reduction due to dam and sustained groundwater decline may reduce food security (~55%); (iii) tipping risk increases due to severe reduction of food security when increasing temperature (>3.5°C) is combined with upstream water withdrawal (30%–50%), subsidy reduction (50%–100%), population growth and political instability. These indicate the need for an SES system perspective for increasing crop production and food security, simultaneously ensuring sustainable water resources and climate change adaptation. The model and findings are useful to achieve food security, and other related SDGs (1&6) in the context of climate change in Bangladesh and similar areas (e.g., Kenya), informed by the consequences of plausible alternative futures.

Anti-Inflammatory Effect of Dietary Pentadecanoic Fatty Acid Supplementation on Inflammatory Bowel Disease in SAMP1/YitFc Mice.

Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn's disease (CD). This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properties in different mouse models of experimental IBD using the SAMP1/YitFc (SAMP) mouse line (14- or 24-week-old), including chronic ileitis and DSS-induced colitis. To quantitively assess the effect of C:15, we tested two dosages of C:15 in selected experiments in comparison to control mice. Intestinal inflammation and intestinal permeability were used as primary outcomes. In ileitis, C:15 supplementation showed an anti-inflammatory effect in SAMP mice (e.g., a reduction in ileitis severity vs. control p < 0.0043), which was reproducible when mice were tested in the DSS model of colitis (e.g., reduced permeability vs. control p < 0.0006). Of relevance, even the short-term C:15 therapy prevented colitis in mice by maintaining body weight, decreasing inflammation, preserving gut integrity, and alleviating colitis signs. Collectively, the findings from both ileitis and colitis in SAMP mice indicate that C:15 may have therapeutic effects in the treatment of IBD (colitis in the short term). This promising effect has major translational potential for the alleviation of IBD in humans.

Exploring the Biocontrol Potential of Phanerochaete chrysosporium against Wheat Crown Rot.

The worldwide occurrence of wheat crown rot, predominantly caused by the pathogen Fusarium pseudograminearum, has a serious impact on wheat production. Numerous microorganisms have been employed as biocontrol agents, exhibiting effectiveness in addressing a wide array of plant pathogens through various pathways. The mycelium of the white-rot fungus Phanerochaete chrysosporium effectively inhibits the growth of F. pseudograminearum by tightly attaching to it and forming specialized penetrating structures. This process leads to the release of intracellular inclusions and the eventual disintegration of pathogen cells. Furthermore, volatile organic compounds and fermentation products produced by P. chrysosporium exhibit antifungal properties. A comprehensive understanding of the mechanisms and modalities of action will facilitate the advancement and implementation of this biocontrol fungus. In order to gain a deeper understanding of the mycoparasitic behavior of P. chrysosporium, transcriptome analyses were conducted to examine the interactions between P. chrysosporium and F. pseudograminearum at 36, 48, and 84 h. During mycoparasitism, the up-regulation of differentially expressed genes (DEGs) encoding fungal cell-wall-degrading enzymes (CWDEs), iron ion binding, and mycotoxins were mainly observed. Moreover, pot experiments revealed that P. chrysosporium not only promoted the growth and quality of wheat but also hindered the colonization of F. pseudograminearum in wheat seedlings. This led to a delay in the development of stem base rot, a reduction in disease severity and incidence, and the activation of the plant's self-defense mechanisms. Our study provides important insights into the biocontrol mechanisms employed by P. chrysosporium against wheat crown rot caused by F. pseudograminearum.

In vivo overexpression of the avian interleukin-17 in a necrotic enteritis disease model modulates the expression of antimicrobial peptides in the small intestine of broilers

In humans and mice, the induction of interleukin (IL)-17 expression enhances epithelial barrier integrity through the secretion of antimicrobial peptides (AMP), thereby improving antibacterial defense. However, it is unclear whether IL-17 has similar antibacterial effects in chickens by modulating the expression of AMPs, such as avian beta-defensins (also known as gallinacins) and cathelicidins. This study evaluated the in vivo effects of inoculating 20-day-old broiler chickens with two doses of a plasmid encoding chicken IL-17 (pCDNA3.1/rchIL-17-V5-HIS TOPO plasmid [pCDNA3.1-IL-17]; 5 or 10 μg/bird). On day 23 of age, all broilers, except those in the negative control group, were orally challenged with a virulent Clostridium perfringens strain for three days. To investigate IL-17-mediated effects against C. perfringens infection, the expression of avian beta-defensin 1 (avBD1), avBD2, avBD4, avBD6, cathelicidins, and inducible nitric oxide synthase (iNOS) genes were quantified, and gross necrotic enteritis (NE) lesion scores were assessed in the small intestine. The results showed that broilers receiving the higher dose of pCDNA3.1-IL-17 (10 μg) had significantly lower NE lesion scores compared to those receiving the lower dose (5 μg), the vector control, and the positive control groups. Furthermore, the expression of all avian beta-defensins and cathelicidin genes was detectable across all groups, regardless of treatment and time points. IL-17 treatment led to significantly higher expression of avBD1, avBD2, avBD4, avBD6, cathelicidin, and iNOS in the duodenum, jejunum, and ileum compared to control chickens. In C. perfringens-infected chickens, the expression of avBD1, avBD2, avBD4, cathelicidin, and iNOS in the ileum was significantly higher than in control chickens. Pre-treatment with the higher dose of pCDNA3.1-IL-17 (10 μg) in infected chickens was associated with reduced NE lesion severity and increased expression of avBD1, avBD2, cathelicidin, and iNOS in the ileum, but not avBD4 and avBD6. These findings provide new insights into the potential effect of IL-17 and reduction in NE lesion severity by modulating AMP expression which may be involved in mediating protective immunity against intestinal infection with C. perfringens.

Matrine protects against experimental autoimmune encephalomyelitis through modulating microglial ferroptosis

Multiple sclerosis (MS) is an inflammatory demyelination neurodegenerative disease of the central nervous system (CNS). Ferroptosis has been implicated in a range of brain disorders, and iron-loaded microglia are frequently found in affected brain regions. However, the molecular mechanisms linking ferroptosis with MS have not been well-defined. The present study seeks to bridge this gap and investigate the impact of matrine (MAT), a herbal medicine with immunomodulatory capacities, on the regulation of oxidative stress and ferroptosis in the CNS of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. CNS of EAE mice contained elevated levels of ferroptosis-related molecules, e.g., MDA, LPCAT3 and PTGS2, but decreased expression of antioxidant molecules, including GSH and SOD, GPX4 and SLC7A11. This pathogenic process was reversed by MAT treatment, together with significant reduction of disease severity and CNS inflammatory demyelination. Furthermore, the expression of PTGS2 and LOX was largely increased in microglia of EAE mice, accompanied with increased production of IL-6 and TNF-α, indicating a proinflammatory phenotype of microglia that undergo oxidative stress/ferroptosis, and their expression was significantly reduced after MAT treatment. Together, our results indicate that ferroptosis/inflammation plays an important role in the pathogenesis of CNS autoimmunity, and inhibiting ferroptosis-induced microglial activation/inflammation could be a novel mechanism underlying the therapeutic effects of MAT on CNS inflammatory demyelination in EAE.

The efficacy of adding some antioxidant compounds in alleviating strawberry fruit rots during storage

BACKGROUND: Postharvest decay caused by Botrytis cinerea (gray mold) and Fusarium solani (fruit decay) negatively affects strawberry fruits during handling and marketing. OBJECTIVE: The effect of cinnamon oil, sodium benzoate, potassium sorbate and/or pomegranate peel powder were estimated on the growth of the two pathogenic fungi and their fruit decay incidence under in vitro and in vivo conditions. METHODS: The isolated fungi from decayed strawberry fruits were identified as Botrytis cinerea and Fusarium sp. The isolated Fusarium sp. was identified molecularly as Fusarium solani and registered in GenBank under accession number ON248575.1 (https://www.ncbi.nlm.nih.gov/nuccore/ON248575.1). RESULTS: Complete fungal growth suppression was observed at a concentration of 3% for all tested materials, Additionally the same (100%) effect was achieved at 2% of a combination of essential oil, salts and pomegranate peel powder. Significant reduction in decay incidence and severity was observed in inoculated strawberry fruits treated with the same concentrations of the tested materials after 10 and 15 days of storage. CONCLUSIONS: The results demonstrate that cinnamon oil, sodium benzoate, potassium sorbate and/or pomegranate peel powder have potency as eco-friendly products, for safe postharvest treatments against strawberry fruit rots during storage. They could be recommended for use in packing-houses due to their wide utilization as safe food preservatives.

Optimization of the intake system for the Setra NS 913 bus

Abstract The paper presents the implementation on buses of a dynamic air transfer system (SDTA) brand Air by Corneliu. That system is the subject of a patent entitled Dynamic Air Transfer Device RO 200900028. At the initiative of the Alba Iulia public Transport society, with a fleet of about 100 buses, we started a study on the efficiency of air intake in the internal combustion engine by implementing an SDTA. Since the air filter location on this bus model, Setra NS 913, is behind the rear axle wheels, the filter is exposed to dust, water and other particles thrown by the drive wheels, which leads to premature clogging and blockage of the filtration area, in the context in which the bus runs mainly on asphalt-free roads. The gas-dynamic resistance (filter permissiveness) would increase considerably, resulting in a severe reduction in the degree of filling of the engine cylinders. In order to eliminate the disadvantages mentioned above, respectively to increase the life of the air filter with implications on the performance of the engine, we have designed a dynamic system consisting of the following components: the air collector, located on the top of the bus; the grid housing, located on the suction grid; tubing, connecting element between the air collector and the grid housing. In order to realize the 3D model of SDTA, the specialized software VISI - CAD / CAM was used.

T-Cell Receptors Cross-Reactive to Coronaviral Epitopes Homologous to the SPR Peptide.

The COVID-19 pandemic caused by the rapid spread of the novel coronavirus SARS-CoV-2, has promoted an interest in studying the T-cell immune response. It was found that the polyclonal and cross-reactive T-cell response against seasonal coronaviruses and other SARS-CoV-2 strains reduced disease severity. We investigated the immunodominant T-cell epitope SPRWYFYYYL from the nucleocapsid protein of SARS-CoV-2. The immune response to this epitope is characterized by the formation of highly homologous (convergent) receptors that have been found in the T-cell receptor (TCR) repertoires of different individuals. This epitope belongs to a group of highly conserved peptides that are rarely mutated in novel SARS-CoV-2 strains and are homologous to the epitopes of seasonal coronaviruses. It has been suggested that the cross-reactive response to homologous peptides contributes to the reduction of COVID-19 severity. However, some investigators have questioned this hypothesis, suggesting that the low affinity of the cross-reactive receptors reduces the strength of the immune response. The aim of this study was to evaluate the effect of amino acid substitutions in the SPR epitope on its binding affinity to specific TCRs. For this, we performed antigen-dependent cellular expansions were performed using samples from four COVID-19-transfected donors and sequenced their TCR repertoires. The resulting SPR-specific repertoire of β-chains in TCRs had a greater sequence diversity than the repertoire of α-chains. However, the TCR repertoires of all four donors contained public receptors, three of which were cloned and used to generate the Jurkat E6-1 TPR cell line. Only one of these receptors was activated by the SPR peptide and recognized with the same affinity by its mutant homologue LPRWYFYYY from seasonal coronaviruses. This indicates that the presence of the mutation did not affect the strength of the immune response, which may explain why the cross-reactive response to the SPR epitope is so frequent and contributes positively to COVID-19 infection.

Prospective prediction of treatment outcomes in adolescents: A head-to-head comparison of alternative model for personality disorder versus borderline personality disorder.

Despite substantial evidence in support of the alternative model for personality disorder (AMPD) that has accumulated over the last decade, a gap remains in terms of head-to-head comparisons of the predictive power of Section II categorical diagnoses versus Section III AMPD diagnoses for clinical outcomes. The current study uses archival data from a naturalistic treatment outcome study in an adolescent psychiatric inpatient sample to compare the predictive power of the Section III AMPD (combined Criterion A and B assessment) versus Section II borderline personality disorder (BPD) in predicting treatment outcomes from admission to discharge. Outcomes in general psychiatric severity and emotion dysregulation were assessed in a sample of 59 adolescents (76.3% female, Mage = 15.27, SD = 1.17) at admission and at discharge on average about a month later. Results showed that, on average, predictive power of both AMPD measures and BPD were relatively modest. However, the AMPD, operationalized through combined measures of identity diffusion and maladaptive traits, was a stronger predictor of reduction in general psychiatric severity than a measure of BPD. The findings of the study add to a growing body of literature pointing to the advantages of Section III AMPD over Section II categorical diagnosis for clinical utility in predicting treatment response. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age.

There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.

Harnessing Abiotic Defence Inducers for Effective Management of Pod Rot of Mungbean

Pod rot is a significant issue for mung bean plants, causing substantial reductions in yield and quality. In this study, several defence inducers, including salicylic acid (SA), nicotinic acid (NA), indole butyric acid (IBA), chitosan, and benzothiadiazole (BTH), were applied as foliar sprays to assess their effectiveness in enhancing resistance to pod rot in field conditions. The results indicated that benzothiadiazole -treated plants experienced a marked reduction in disease severity of 18.667% compared to untreated plants (control) with 36.177%. This indicated that benzothiadiazole has antifungal properties, decreases disease severity, and stimulates defence mechanisms in Mung bean against pod rot.

Outcomes of mitral transcatheter edge to edge repair with MitraClip™ – An Indian single center experience

ObjectiveTo evaluate the outcomes of transcatheter edge-to-edge repair (TEER) with MitraClip™ (Abbott Vascular) in symptomatic high surgical risk Indian patients with significant mitral regurgitation (MR). MethodsPatients with moderately severe or severe primary or secondary MR and deemed high surgical risk were treated with MitraClip™. The data were collected retrospectively from medical records. The primary outcome was technical success, and secondary outcomes were ≤2+ MR reduction and improvement in functional capacity at 30 days. ResultsBetween November 2018 and August 2023, 64 patients were treated with MitraClipTM. The mean age was 70.0 ± 12.1 years and 64 % were males. The mean EuroScore II and STS score predicted mortality for mitral valve repair were 5.8 ± 4.5 % and 4.0 ± 3.8 % respectively. MR etiology was primary in 56.3 %, secondary in 40.6 % and mixed in 3.1 %. The device was implanted successfully in all but one patient with technical success rate of 98.4 %. The average number of clips per patient was 1.5 ± 0.6 and 42.2 % patients received more than one clip. The mean mitral valve gradient was 3.5 ± 1.6 mmHg. The MR severity of ≤2+ was achieved in 91.8 % of the subjects and similar proportion were in New York Heart Association Functional Class I or II at 30 days. ConclusionIn high-risk Indian patients with symptomatic significant MR, TEER with MitraClip™ was achieved with a high technical success rate. It was associated with significant reduction in MR severity and improvement in functional capacity in >90 % of the subjects.