Hereditary Hemochromatosis Unmasked by Yersiniosis: Report of Three CasesKaram Karam1, Elias Fiani2*[1] Department of Gastroenterology, University of Balamand, Beirut, Lebanon. Email: [email protected][2] Associate Professor, Department of Gastroenterology, University of Balamand, Beirut, Lebanon. Email: [email protected] *CORRESPONDING AUTHORKey Clinical Message: Yersiniosis has a causal relationship with hereditary hemochromatosis (HH). Physicians should have a high index of suspicion for the diagnosis of HH when approaching a patient with yersiniosis in the setting of high ferritin levels and increased iron saturation. Yersiniosis serves as a precursor for the diagnosis of HH.Keywords: Hereditary Hemochromatosis; Yersinia Enterocolitica ; HFE Genetic Testing; Phlebotomy; Case Series.

Consider the nonlinear difference equations of the form L u = f m ( u ) , m ∈ Z , where L is a Jacobi operator given by L u m = a m u m + 1 + a m − 1 u m − 1 + b m u m for m∈Z, { a m } and { b m } are real valued T-periodic sequences, and f:Z×R→R. Applying critical point theory and a new analytical method, we obtain that the above problem has ground state solutions and infinitely many geometrically distinct solutions under the local superlinear condition lim | x | → ∞ ∫ 0 x f m ( t ) dt | x | 2 = ∞ uniformly in m∈ D for some set D⊂Z instead of the global superlinear condition lim | x | → ∞ ∫ 0 x f m ( t ) dt | x | 2 = ∞ uniformly in m∈Z.

Purpose: Pulmonary hypertension (PH) is a chronic complications of sickle cell disease (SCD) with limited known biomarkers, beyond increases in plasma brain natriuretic peptide levels. Experimental Design: We conducted a proof-of-concept study to identify serum protein biomarkers that were differentially expressed in SCD patients with elevated tricuspid regurgitation velocity (TRV – a noninvasive marker of PH). Results: We found 41 out of 92 target proteins that were significantly different between the non-elevated (TRV≤2.6 m/sec; N = 35) and highly elevated TRV group (TRV≥2.9 m/sec; N = 35, p<0.05). Six of them passed a Bonferroni correction (p value < 0.0005) including T-cell surface glycoprotein, lymphotactin, SLAM family member 7, galectin-9, TNF-related apoptosis-inducing ligand receptor 2, and tumor necrosis factor receptor superfamily member 11A . We observed up to a 1.2-fold increase in the high TRV group for these six proteins. These six proteins had strong positive correlation with serum NT-proBNP levels (a positive control marker elevated in PH (r >= 0.44). Additionally, these markers correlated with other clinical parameters of PH in SCD. Conclusion: Circulatory protein markers of the immune response are increased in SCD patients with elevated TRV as compared to those without elevated TRV.

Background Nirsevimab, a novel monoclonal antibody, provides passive immunity against RSV-infections in infants. In October/2023, Spain adopted immunization for children <6 months and those born during the epidemic season. Our main goal was to compare clinical, epidemiological and virological characteristics of respiratory infections in hospitalized infants before and after nirsevimab introduction. Methods. A prospective study was conducted in two Madrid hospitals during the 2022-23 and 2023-24 epidemic seasons. Infants <12 months admitted with lower respiratory tract infections were included. Clinical, epidemiological, and virological characteristics were compared based on admission before or after nirsevimab introduction and whether they received it. Results A total of 717 infants were included: 526 before October/2023 and 191 thereafter. Admissions from October-March 2023/24 decreased by 59% (95%CI:58.7-62.3%) compared to October-March 2022/23. ICU admissions dropped by 74% (95%CI:70.7-77.3%). Of those hospitalized after October/2023, 55(28.8%) received nirsevimab, with 11(20%) contracting RSV. The RSV-detection rate was lower after October/2023 (39% vs. 65%, P<0.001), as was the detection of other respiratory viruses, except rhinovirus and human bocavirus. Patients admitted after October/2023 were older (P=0.002), included fewer infants under 1 month (P=0.005), and had shorter hospital stays (P=0.001). For infants under 3 months, the likelihood of needing a stay > 5 days was 70% lower compared to those admitted before October/2023 (P<0.001;OR:0.39, 95%CI:0.22-0.66). Conclusions Nirsevimab has shown considerable effectiveness in shielding young infants from severe outcomes linked to RSV-infection. Furthermore, our study observed a notable decrease in hospitalizations for infections caused by other respiratory viruses after the introduction of nirsevimab.

Models of infectious disease dynamics suggest that treatment, vaccination, and isolation are required for the control of infectious diseases. Considering that vaccination is one of the most effective methods to control infectious diseases, it is often not possible to rapidly vaccinate all susceptible populations in the early stages of the spread of infectious diseases due to the limitation of the number of vaccines, insufficient medical personnel, or the slow progress of vaccination efforts. Our simulation analysis by building an SVIWRD model found that the degree of negative impact of infectious diseases shown when young and old people were divided into two populations and vaccinated at different rates was different.Therefore, for the current problem of continued spread of COVID-19, we consider the infectious disease dynamics model to achieve the goal of making the risk of infection of COVID-19 lower by controlling the proportion of vaccination of elderly and young people. In this paper, we divided young and old people into two groups, established an SVIWRD model, performed single-objective optimization using Pontryagin's maximum principle, and used the Runge-Kutta method for numerical calculation and simulation, so as to arrive at a certain vaccination ratio that plays the effect of reduced negative impact of COVID-19.

Guerbet alcohol (GA) is β-branched primary alcohol having excellent physiochemical properties like lower pour point (PP) and higher kinematic viscosity (KV) in comparison to linear alcohol. Although different aspects of the synthesis of GA, such as methods of synthesis, catalytic systems, and reaction conditions, have been studied, but statistical modeling and optimization of the synthesis of GA have not been carried out. In the present work, the optimization of the synthesis of GA using a mixture of lauryl and myristyl alcohol was carried out with the aid of response surface methodology (RSM) considering the conversion of the reaction, PP and KV at 40˚C & 100˚C as dependent variables. The optimal reaction conditions were temperature, pressure, and time of 220˚C, 300 mbar, and 10 hours respectively. The optimum conversion was 99.141%, including dimer yield of 81.755%, PP of -3˚C, KV at 40˚C & 100˚C of 34.12 cSt & 7.22 cSt, respectively. The results obtained by the RSM were then authenticated, applying artificial neural networks (ANN) generated with the help of MATLAB. The ability of the generated model to predict the response variables was validated by less than 5% error for almost all the models, confirming the statistical significance. Also, the tribological potential for linear Ginol-12,14 (FA) and synthesized branched GA as lubricant additive was evaluated by determining its physiochemical, thermal and tribological properties.

Robots have a profound impact on human production and life, which have been developed by leaps and bounds in recent decades. The original robot is large and requires a wired power supply to drive, whose working space and functions are limited. As the higher and higher requirements for operations in complex environments, researchers continue to develop wireless driven miniature robots. In this paper, the ratio and deformation properties of PNIPAM and PEGDA hydrogels were researched, and the microcrawls and microgrippers with 3D structure were prepared. They have light stimulus response and magnetic response characteristics, and can be reversibly transformed from 3D to two-dimensional structure to complete crawling and transportation functions. Highlights: 1. PNIPAM-PEGDA bilayer structure with photo-magnetic response was prepared based on secondary curing technology. 2. The optimal ratio and thickness of PNIPAM hydrogel were studied. 3. Crawler and gripper were made based on the bilayer structure for transport.

A document by Maryam Sahibqran. Click on the document to view its contents.

A document by Francisco-J Renero-C. Click on the document to view its contents.

The incidence of multiple primary malignancies (MPMs) associated with colorectal cancer (CRC) varies, ranging from 3.0% to 17.0%, with synchronous MPMs occurring at rates of 1.0% to 4.41%. The incidence of MPMs was found to be higher in male and older CRC patients. However, age-related findings are inconsistent, with some studies indicating a higher risk in younger CRC patients, possibly linked to genetic aberrations and carcinogen exposure. The field cancerization theory, chemotherapy, and radiotherapy demonstrated associations with the occurrence of MPMs. Genetic analyses emphasizing microsatellite instability (MSI), CpG island methylation phenotype (CIMP), chromosomal translocations, and p53 mutations as potential contributors to the development of MPMs associated with CRC. Prognostically, MPMs associated with CRC, especially synchronous cases, are linked to lower survival rates, primarily attributed to postoperative complications.

Background Study on the effect of hydroxychloroquine (HCQ) in treating children with chronic immune thrombocytopenia (ITP) is limited. The association between ANA positivity and its efficacy is not clear. Methods This was a retrospective cohort study on chronic ITP children. We compared the clinical characteristics of patients who received HCQ with those who didn’t, as well as patients who responded to HCQ at 3 months with those who didn’t. Mixed-effects models were performed to assess the effect of HCQ on platelet counts and the association between ANA and its efficacy. Records of side effects associated with HCQ were reviewed. Results A total of 191 children with chronic ITP were included in this study, involved 42 patients who received HCQ. In patients who received HCQ, 69.0% of patients achieved complete response /response at the last follow-up, with a higher frequency than in patients who didn’t (69.0% vs. 48.3%). The overall response rate was 56.8% at 3 months and 40.5% at 1 year. Our results showed no difference in ANA positivity between patients with response to HCQ and those without. HCQ was effective for increasing platelet counts (mean difference: 23.82×109/L; 95% CI: 7.44 ~ 40.21), but the association between ANA positivity and its efficacy was not found. Side effects were recorded in 6 of 42 patients (14.3%). Conclusions HCQ was associated with increased platelet counts in chronic ITP children. The baseline ANA level was not found to have an interaction effect on this efficacy. Side effects of HCQ should be concerned.

Pan-tilt-zoom (PTZ) cameras, which dynamically adjust their field of view (FOV), are pervasive in large-scale scenes, such as train stations, squares, and airports. In real scenarios, PTZ cameras are required to quickly make decisions informed about where to direct its focus through contextual cues from the surrounding environment. To achieve this goal, some researches project camera videos into three-dimensional (3D) models or panoramas and allow operators to perceive spatial relationships. However, these works face several challenges in terms of real-time processing, localization accuracy, and realistic reference. To address this problem, we propose a visual expansion and real-time calibration for PTZ cameras assisted by panoramic models. We attempt to meet the demand for real-time processing with a motion estimation model for a PTZ camera, to improve calibration performance of PTZ images with only two feature point pairs, and to provide a realistic environmental context through a panoramic model. We verify our methods on both public and our self-built test scene. It can be seen from the experimental results that our method can exhibit impressive accuracy and efficiency.

Background and aim: The reflux symptoms score -12 (RSS-12) is a validated questionnaire with good sensitivity and specificity for diagnosing laryngopharyngeal reflux disease (LPRD). However, the correlation between RSS-12 and reflux finding score (RFS) in patients with clinical symptoms suggestive of LPR has not been investigated. In this study, we examined such correlation. Patients and methods: We conducted cohort cross sectional study over 6 months duration in total of 105 patients with typical gastroesophageal reflux disease (GERD ) symptoms associated with LPR symptoms based on RSS-12.We excluded patients with any medical problems or lifestyle habits that could induce similar symptoms. The study participants underwent a telescopic laryngeal examination and the RFS was calculated. Results: The prevalence of LPRD (RFS > 7) in patients with clinical symptoms of GERD and LPR was 14.2% (15 patients). Laryngoscopic abnormalities unrelated to LPRD were present in 16 patients (15.2%). RSS-12 had strong positive correlation with RFS. Conclusion: In patients with clinical symptoms of LPR, RSS-12 strongly predicts the diagnosis of LPRD.

cyber resilience is an interdisciplinary topic of study that aims to maintain security and stability in digital environments. This paper examines the increasing complexity and vulnerability of socio-technical systems to assaults, underscoring the necessity for robust cyber resilience strategies. The study highlights the need of cybersecurity for business resilience due to the increasing security risks posed by digital transformation and emerging technologies like big data, block chain, and artificial intelligence. It explores the fundamental concepts of operational and organizational resilience in addition to the stages of the cyber resilience cycle. The paper also delves into data resiliency and data recovery, emphasizing their importance in mitigating the impact of data breaches, natural disasters, and human errors. Key strategies for resilient data recovery are outlined, including automated backups, encryption, continuous data protection, and the integration of Disaster Recovery as a Service (DRaaS). A disaster recovery model for CRM using cloud computing and SaaS is proposed, addressing latency and data loss issues while ensuring continuous service availability. The study underscores the significance of proactive data security measures and collaboration between IT teams and executives to safeguard organizational data and maintain business continuity.

Viral accessory proteins play critical roles in viral escape form host innate immune responses and in viral inflammatory pathogenesis. Here we show that the SARS-CoV-2 accessory protein, ORF9b, but not other SARS-CoV-2 accessory proteins (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome-dependent caspase-1 in A549 lung carcinoma cells and THP-1 monocyte-macrophage cells. Exposure to lipopolysaccharide (LPS) and ATP additively enhanced the activation of caspase-1 by ORF9b, suggesting that ORF9b and LPS follow parallel pathways in the activation of the inflammasome and caspase-1. Following rational in silico approaches, we have designed small molecules capable of inhibiting the homodimerization of ORF9b, which experimentally inhibited ORF9b-ORF9b homotypic interactions, caused mitochondrial eviction of ORF9b, inhibited ORF9b-induced activation of caspase-1 in A549 and THP-1 cells, cytokine release in THP-1 cells, and restored type I interferon (IFN-I) signaling suppressed by ORF9b in both cell models. These small molecules are first-in-class compounds targeting a viral accessory protein critical for viral-induced exacerbated inflammation and escape from innate immune responses, with the potential of mitigating the severe immunopathogenic damage induced by highly pathogenic coronaviruses and restoring antiviral innate immune responses curtailed by viral infection.

Worry and rumination are common forms of perseverative cognition (PC) and repetitive negative thinking towards stressors. PC can generate psychophysiological stress before or after exposure to stressors and is linked to chronic stress, diseases, and adverse health outcomes. PC has been associated with vagally-mediated heart rate variability (vmHRV). In the present meta-analytic review, effect sizes for the relationship between PC and vmHRV were computed for baseline, stressor, and recovery conditions vmHRV among studies using within-subject and between-subject analyses. A total of 55 effect sizes were extracted from 24 eligible articles (17 for baseline, 15 for reactivity, 8 for recovery). Small to medium effect sizes were observed for the correlations between PC and baseline vmHRV (g = .40, SE = .10), within-subject reactivity vmHRV (g = .27, SE = .07), and between-subject recovery vmHRV (g = .44, SE = .18). The other meta-analyses did not yield statistically significant effect sizes. High heterogeneity was detected across the meta-analyses and statistical tests suggested the absence of publication biases. Overall, PC in laboratory studies was observed to differentially associate with baseline, reactivity, and recovery vmHRV. The scarcity of vmHRV recovery studies was discussed.

The cortical somatostatin interneuron population includes several diverse cell types, among them the Martinotti cells. Layer-specific differences in connectivity and function between different subtypes of Martinotti cells are becoming apparent, which require contemporary studies to investigate cortical interneurons in a layer and subtype specific manner. In this study, we investigate the connectivity of a subtype of Chrna2+ layer 5 Martinotti cells in the primary motor cortex, using a monosynaptic retrograde rabies viral tracer. We found direct input from pyramidal cells and local parvalbumin interneurons. In addition, we found long-range direct inputs from the motor thalamus, substantia innominata of the basal forebrain and globus pallidus. Based on the observed input pattern, we tested and found an increased number of falls in the hanging wire test upon temporary overexcitation of Chrna2+ layer 5 Martinotti cells. These results suggest that Chrna2+ Martinotti cells in the motor cortex are involved in sensorimotor integration.

Spinal cord stimulation is a functional neurosurgery proposed for treating motor symptoms in patients with Parkinson’s disease, yet the mechanisms underlying motor symptom relief have not been elucidated. While preclinical studies suggest that long-term motor improvements may be due to neuroprotection of the nigrostriatal pathway, this evidence is limited to neurotoxic models. To evaluate the effect of spinal cord stimulation on nigrostriatal pathway neuroprotection in a genetic model of Parkinson’s disease, male Sprague-Dawley rats were unilaterally injected into the substantia nigra with empty or α-synuclein-coding adeno-associated viruses. Thirty-two days later, the rats were treated with 300 Hz spinal cord stimulation for ten weeks (two sessions/week). Ninety-one days post-injection treated α-synuclein rats had better motor performance than the untreated group, and no differences compared to the control group. However, spinal cord stimulation could not counteract the loss of dopaminergic neurons in the nigrostriatal pathway and did not cause changes in the total dopamine levels in the striatum, dopamine transporter, or tyrosine hydroxylase expression in the substantia nigra. The current study suggests that spinal cord stimulation prevents motor impairment in a genetic model of PD through a mechanism independent of the nigrostriatal pathway degeneration induced by α-synuclein overexpression.