Search Results (43)

Scrub typhus, caused by Orientia tsutsugamushi, remains a neglected cause of acute febrile illness. Molecular testing of blood supports early diagnosis, yet once doxycycline is started, blood qPCR positivity can drop rapidly, complicating short-term follow-up and relapse surveillance. We compared detection across multiple clinical specimens and evaluated nasopharyngeal swabs (NPSs) as noninvasive supplementary specimens during treatment initiation. In a prospective single-center cohort from Hainan, China, we enrolled 20 patients with scrub typhus. Blood, NPS, urine, and stool were collected before doxycycline administration 24 h after the first dose and on day 5. qPCR was performed for the analysis of Orientia tsutsugamushi. qPCR-positive specimens were subjected to nested PCR targeting TSA56, and nested PCR-positive amplicons were Sanger sequenced for genotyping. Before treatment, O. tsutsugamushi DNA was detected in 15/20 blood samples (75.00%) and 5/20 NPS samples (25.00%), but 0/20 urine samples (0%) and 0/20 stool samples (0%). At 24 h after treatment, detection in blood was 0/20 (0%) while NPS samples were positive in 3/20 (15.00%). All specimens were negative by day 5 after treatment. Across sequenced NPS positives (n = 3), Karp 2/3 (66.77%) and Gilliam 1/3 (33.33%) predominated. In paired blood–NPS positives, inter-specimen homology was high (percentage nucleotide identity 100% for Karp and 100% for Gilliam). NPS is not sensitive enough for primary diagnosis; however, within the first 24 h after doxycycline it offers a practical, noninvasive supplementary specimen to support short-term follow-up and community-based sampling when venipuncture or transport are constrained. Larger, multi-center studies are warranted to refine sampling windows and diagnostic performance. Full article

Background: Patients with inflammatory rheumatic diseases (IRD) are susceptible to influenza infections and their complications. However, they may avoid vaccination for fear of exacerbating their IRD. This study evaluates the 2023/24 influenza vaccine in IRD patients, aiming to provide recommendations for this group in the upcoming season. Methods: In this prospective, longitudinal study, we assessed the self-reported impact of influenza vaccination on patients with IRD. Participants were recruited nationwide between October and December 2023 and completed an online questionnaire after vaccination as well as at three and six months of follow-up. Results: Among 633 patients, 87.5% were female, with a median age of 50.4 (18–84) years. Post-vaccination, 50% experienced injection site pain; 41% reported no side effects. IRD flares occurred in 5%, with 1% requiring changes to immunomodulation. Among 428 patients with follow-up, influenza infections were reported in 38 patients (8.9%), including 10 (2.3%) with reinfections. No severe cases requiring hospitalization were reported. Spondyloarthritis patients had higher susceptibility to influenza (p = 0.002), accounting for 55.3% of infections. IRD flare-ups in the 12 months before vaccination predicted infections (p = 0.002). Conclusions: The 2023/24 vaccine was well tolerated by IRD patients, with no impact on the course of the disease in 95% of cases. Only 9% of patients reported influenza infections, none of which were severe. In light of these findings, physicians are advised to recommend vaccination to eligible IRD patients prior to or in the respective season. Full article

Scrub typhus, caused by Orientia tsutsugamushi (Ot), is a re-emerging public health concern across Southeast Asia. Although multiple Ot strains have been identified in endemic regions, their genetic characterization in India remains limited. We analyzed Ot strains from humans by targeting the GroEL and 56-kDa TSA genes. A total of 105 serum samples were subjected to PCR amplification and phylogenetic analysis for the GroEL gene, of which 33 (31.4%) were positive. Phylogenetic reconstruction revealed four major clades: Karp, Kato, Ot-TJTN (novel Ot-Thanjavur-Tamil Nadu), and the Gilliam group. Among the 33 PCR positives, 11 sequences clustered into a distinct monophyletic clade within the Gilliam group but diverged significantly from known classical Gilliam strains. The overall mean nucleotide diversity (π) was 0.02 (2%), while the divergence between these 11 sequences and the Gilliam strain was 0.039 (3.9%). The observed divergence indicates that these sequences represent the first identified Indian Gilliam variant (IG-v), showing marked genetic distinction from classical Gilliam and other related strains. Further analysis of the 56-kDa gene from the 11 IG-v samples revealed phylogenetic incongruence between the GroEL and 56-kDa genes, indicating antigenic reassortment involving three clades: Karp-like (n = 7), Ot-TJTN-like (n = 3), and Gilliam (n = 1). Similarity plot and recombination analyses, using 56-kDa Ot-TJTN and Karp-like clades as queries, against Ot reference strains revealed preliminary evidence of genetic exchange. These findings highlight the possible role of recombination and antigenic shift in driving the evolutionary dynamics and genetic diversity of Ot in this region. Notably, the identification of an IG-v marks a significant advancement in our understanding of the circulating Ot strains. This finding holds important implications for refining molecular diagnostics, enhancing serological assays, and developing broadly protective vaccines targeting region-specific variants. Full article

This paper presents a comprehensive strategy for addressing tracking and disturbance rejection for both lumped and distributed parameter systems, focusing on infinite-dimensional input and output spaces. Building on the geometric theory of regulation, the proposed methodology employs a cascade algorithm coupled with Tikhonov regularization to derive control laws that improve tracking accuracy iteratively. Unlike traditional optimal control approaches, the framework minimizes the limsup in time of the tracking error norm, rather than with respect to a quadratic cost function. It is important to note that this work also includes applicability to over- and under-determined systems. We provide theoretical insights, detailed algorithmic formulations, and numerical simulations to demonstrate the effectiveness and generality of the method. Results indicate that the cascade controls asymptotically approximate the classical optimal control solutions, with limitations addressed through rigorous error analysis. Applications include diverse scenarios with both finite and infinite-dimensional input and output spaces, showcasing the versatility of the approach. Full article

Conventional vibrational systems associated with proprioception are mostly equipped with a single standard frequency and amplitude. This feature often fails to show kinesthetic illusion on different subjects, as different individuals respond to different frequencies and amplitudes. Additionally, different muscle groups may also require the flexibility of frequencies and amplitudes. We developed a custom vibrational system that is equipped with flexible frequency and amplitude, adapted to a custom graphical user interface (GUI). Based on the user’s criteria, the proposed vibrational system enables a wide range of frequencies and amplitudes that can be swept under a single platform. In addition, the system uses small linear actuators that are wearable and attach to the subject without the need for restrictive straps. The vibrational system was used to model trunk proprioceptive impairment associated with low back pain. Low back pain is the leading cause of disability worldwide. It is mostly associated with impaired postural control of the trunk. For postural control, the somatosensory system transmits proprioceptive (position sense) information from the sensors in the skin, joints, muscles, and tendons. Proprioceptive studies on trunk muscles have been conducted where the application of vibration at a set amplitude and frequency across all participants resulted in altered proprioception and a kinesthetic illusion, but not in all individuals. To assess the feasibility of the system, we manipulated the trunk proprioception of five subjects, demonstrating that the vibrational system is capable of modulating trunk proprioception and the value of customizing parameters of the system to obtain maximal deficits from individual subjects. Full article

Introduction: Scrub typhus is caused by Gram-negative bacteria, Orientia tsutsugamushi. Humans are the dead-end host of scrub typhus. Currently, there is no vaccine available. The disease can be fatal without appropriate treatment. Here, we present the circulating OT genotypes in Malaysia and a tsa56-based single PCR to detect and determine OT genotypes, which is an approach to replace the time-consuming traditional nested PCR. Methods: The patients’ blood or tissue samples (n = 1200), received from all hospitals in Malaysia from December 2022 to November 2024, were screened for rickettsial infections. Both htrA qPCR and nested PCR were performed to detect the presence of OT DNA. Simultaneously, a selection of DNA was evaluated for the new single PCR protocol and confirmed with Sanger sequencing. Results: We report that Pahang state of Peninsular Malaysia presents the highest number of acute scrub typhus infections in Malaysia within the 24 months period. There are four genotypes circulating in the Malaysian population. OT genotype Gilliam (n = 31, 29.2%) and Karp (n = 31, 29.2%) are the predominant OT genotypes in Malaysia, followed by TA763 (n = 22, 20.8%) and Kato (n = 22, 20.8%). The single-run PCR presents longer sequence size and similar results with the nested PCR. Conclusions: Acute scrub typhus infection is not rare in Malaysia and should be considered for undifferentiated febrile illness. The single-run PCR protocol is time-saving and a promising approach for OT detection and genotype analysis in a single run to complement a clinical diagnostic setting and surveillance. Full article

Antioxidants are critical components of the body’s defense system, providing protection against cell-damaging free radicals responsible for oxidative damage of biomolecules. Humans benefit from the consumption of plants with high antioxidant content, which have been shown to positively impact health. In plant physiology, antioxidants provide protection from biotic and abiotic stress, particularly during the development of seeds and germination. Peanut seeds and seed coats have been shown to contain several beneficial antioxidants and are a good source of phytonutrients. Seed coat color can vary greatly and impact the antioxidant capacity of the edible portion of the peanut. Additionally, the seed coat can provide bitter notes in products, affecting their palatability and potentially negating the beneficial properties of the antioxidants present. A total of 42 accessions from the Germplasm Resource Information Network (GRIN) with a variety of seed coat colors were obtained and analyzed for total antioxidant capacity to provide a baseline assessment of the distribution of antioxidants in kernel versus seed coats. The results demonstrated that seed coat color somewhat impacts antioxidant capacity, and 56–88% of the total antioxidant capacity resides in the seed kernel. Three control samples, not part of the germplasm collection, were roasted and prepared for analysis by the descriptive sensory panel. Seed coats were added back to the roasted paste in increasing proportion for analysis by the panel, and perceptions regarding bitterness and overall organoleptic properties were noted. Based on the results of this study, several accessions were selected and then planted for increase and potential crossbreeding with appropriate commercial cultivars. This information could be used to selectively add antioxidant capacity to peanut breeding programs to provide additional health benefits to consumers without compromising the sensory perception and desirability and peanut products in nutrition. Full article

Objective: Cholesin is a recently discovered gut-derived hormone secreted by enterocytes upon dietary cholesterol uptake via the transmembrane sterol transporter Niemann–Pick disease C1-like intracellular cholesterol transporter 1 (NPC1L1). In the liver, cholesin activates G protein-coupled receptor 146 (GPR146), causing reduced cholesterol synthesis. In this exploratory, hypothesis-generating study based on post hoc analysis, human data on the cholesin system are presented. Methods: Mucosal biopsies were collected throughout the intestinal tract from 12 individuals with type 2 diabetes (T2D) and 12 healthy, matched controls. Upper small intestinal mucosal biopsies were collected from 20 individuals before and after Roux-en-Y gastric bypass (RYGB) surgery. Liver biopsies were collected from 12 men with obesity and 15 matched controls without obesity. Subcutaneous abdominal adipose tissue biopsies were collected from 20 men with type 1 diabetes (T1D). All biopsies underwent full mRNA sequencing. Results: Cholesin mRNA expression was observed throughout the intestinal tracts of the individuals with T2D and the controls, in the livers of men with and without obesity, and in adipose tissue of men with T1D. NPC1L1 mRNA expression was robust throughout the small intestines but negligible in the large intestines of both individuals with and without T2D. RYGB surgery induced the expression of NPC1L1 mRNA in the upper small intestine. GPR146 mRNA was expressed in the livers of men, both with and without obesity, and in the adipose tissue of men with T1D, but not in the intestines. Conclusions: Our results suggest a role of the cholesin system in human physiology, but whether it is perturbed in metabolic diseases remains unknown. Clinical trial registration numbers: NCT03044860, NCT03093298, NCT02337660, NCT03734718. Full article

Scrub typhus is a mite-borne, re-emerging public health problem in India, particularly in Tamil Nadu, South India. More than 40 serotypes of Orientia tsutsugamushi have been documented worldwide. However, the information on the circulation of its molecular sub-types in India is scanty. A retrospective study was conducted among serologically confirmed cases of scrub typhus. DNA isolated from blood was screened by a nested polymerase chain reaction (nPCR) targeting the GroEL and the 56 kDa type-specific antigen (TSA) genes. Out of 59 samples, 14 partial fragments of GroEL and the twelve 56 kDa genes were PCR-amplified and DNA-sequenced. The neighbor-joining (NJ) analysis indicated three distinct phylogenetic clades, including a novel genotype designated as Ot-Thanjavur-Tamil Nadu (Ot-TJTN, 9 nos. 64.3%); Karp-like (4 nos. 28.6%); and Kuroki-Gilliam type (1 no. 7.1%). Also, phylogenetic analysis of twelve 56 kDa variable domains (VDΙ-ΙΙΙ) of TSA gene sequences revealed a distinctive new genotypic cluster of eight samples (66.6%), and the remaining four (33.4%) were Karp-like genotypes. The Simplot analysis for the similarity and event of recombination testing elucidated the existence of the new genotype of the Ot-TJTN cluster, which was undescribed so far, in the Kato and TA716 lineages. The significant findings recommend further studies to understand the ongoing transmission dynamics of different O. tsutsugamushi strains in vector mites, rodent hosts, and humans in this region. Full article

This study examined the impact of personalizing muscle vibration parameters on trunk control. We assessed how altered trunk extensor muscle (TEM) proprioception affects seated trunk control in healthy controls (HCs). To explore the link between altered TEM proprioception and impaired trunk control in chronic low back pain (cLBP), we performed equivalence testing between HCs undergoing TEM vibration and cLBP without vibration. Twenty HCs performed active joint reposition error (AJRE) testing to determine personalized vibration parameters. Each participant maintained balance on an unstable chair with eyes open and closed, with and without TEM vibration. We compared trunk control between HCs and twenty age- and sex-matched cLBP participants, using mean velocity and 95% confidence ellipse area of center-of-pressure changes to quantify trunk postural control. Equivalence was examined by comparing mean difference scores to minimal detectable change values and calculating between-group effect sizes. Personalized vibration parameters led to larger lumbopelvic repositioning errors (d = 0.89) than any single vibration frequency (d = 0.31–0.36). In healthy adults with no back pain, vision had large effects on postural control (η_p² = 0.604–0.842), but TEM vibration had no significant effects (p > 0.105) or interactions with vision (p > 0.423). Between-group effect sizes (d = 0.32–0.51) exceeded our threshold for performance equivalence (d < 0.2). Muscle vibration altered position sense during AJRE testing, and personalizing parameters amplified this effect. However, TEM vibration had minimal impact on seated trunk postural control in adults with no back pain and did not lead to performance degradation comparable to that in cLBP. Full article

Physiological maturity impacts seed quality through various mechanisms including vigor, desiccation tolerance, dormancy induction, synthesis of raw materials (including seed storage proteins), and the reorganization of metabolisms. Peanut seed development can be classified into seven classes with four incremental stages per class. Based on the mesocarp color, the final three stages are commonly referred to as “orange”, “brown”, and “black”. In 2017, freshly harvested pods from one genotype of runner market-type peanuts grown under conventional practices were obtained from the University of Georgia research facility. The pods were removed from the plant material and ‘pod blasted’ to reveal the mesocarp. After separation, the remainder of the pod outer layer was removed, and the seeds were segregated for proteomic analysis. The raw peanuts were analyzed by bottom-up LC-MS/MS proteomics, which was conducted by the Proteomics Resource Center at the Rockefeller University, to identify the significant protein composition differences in each maturity class. The proteomic data revealed differentially expressed proteins as a function of maturity class with multiple functions including plant defense, metabolism, cell signaling, nutrient accumulation, and packaging. Understanding the processes needed for seed maturation will enable peanut scientists to evaluate the traits needed for robust germination, hardiness of the seed in response to disease, and nutrient quality. Full article

Autism spectrum disorder (ASD) exhibits diverse manifestations influenced by demographic factors. This study evaluates these variations within Saudi Arabia, aiming to investigate language, speech and behaviour characteristics across different demographics in Saudi Arabia using the Arabic Version of the Gilliam Autism Rating Scale—Third Edition (A-GARS-3). Employing a cross-sectional design, 178 participants were stratified by developmental status (n = 124 school settings, n = 54 clinical setting), sex (Females = 77, Males =101), age (range = 3–22), and geographical region (different provinces in Saudi Arabia). The A-GARS-3 measured ASD manifestations across six subscales. The study identified significant differences in ASD manifestations by developmental status, with higher ASD likelihood and severity in clinical settings. Younger children showed more pronounced ASD characteristics, and males were slightly more likely to be diagnosed with ASD. Geographical analysis revealed regional differences in severity. The findings underline the importance of demographic considerations in ASD assessment and diagnosis, suggesting the need for age-specific and culturally sensitive approaches. The A-GARS-3 is a reliable tool for the Saudi context. Regional disparities in ASD prevalence and severity indicate a need for tailored health policies and resources across Saudi provinces. Full article

Scrub typhus is a re-emerging disease caused by Orientia tsutsugamushi, transmitted by mites belonging to the family Trombiculidae. Humans and rodents acquire the infection by the bite of larval mites/chiggers. Suncus murinus, the Asian house shrew, has been reported to harbor the vector mites and has been naturally infected with O. tsutsugamushi. The present study aimed to localize and record O. tsutsugamushi in the tissues and the host response in shrews naturally infected with O. tsutsugamushi. Sheehan’s modified May–Grunwald Giemsa staining was carried out in 365 tissues from 87 animals, and rickettsiae were documented in 87 tissues from 20 animals. Immunohistochemical (IHC) staining, using polyclonal antibodies raised against selected epitopes of the 56-kDa antigen, was carried out, and 81/87 tissue sections were tested positive for O. tsutsugamushi. By IHC, in addition to the endothelium, the pathogen was also demonstrated by IHC in cardiomyocytes, the bronchiolar epithelium, stroma of the lungs, hepatocytes, the bile duct epithelium, the epithelium and goblet cells of intestine, the tubular epithelium of the kidney, and splenic macrophages. Furthermore, the pathogen was confirmed by real-time PCR using blood (n = 20) and tissues (n = 81) of the IHC-positive animals. None of the blood samples and only 22 out of 81 IHC-positive tissues were tested positive by PCR. By nucleotide sequencing of the 56-kDa gene, Gilliam and Karp strains were found circulating among these animals. Although these bacterial strains are highly virulent and cause a wide range of pathological alterations, hence exploring their adaptive mechanisms of survival in shrews will be of significance. Given that the pathogen localizes in various organs following a transient bacteremia, we recommend the inclusion of tissues from the heart, lung, intestine, and kidney of reservoir animals, in addition to blood samples, for future molecular surveillance of scrub typhus. Full article

Bovine viral diarrhea virus (BVDV) induces immunosuppression and thymus depletion in calves. This study explores the impact of prior BVDV-2 exposure on the subsequent immune response to influenza D virus (IDV). Twenty 3-week-old calves were divided into four groups. Calves in G1 and G3 were mock-treated on day 0, while calves in G2 and G4 received BVDV. Calves in G1 (mock) and G2 (BVDV) were necropsied on day 13 post-infection. IDV was inoculated on day 21 in G3 calves (mock + IDV) and G4 (BVDV + IDV) and necropsy was conducted on day 42. Pre-exposed BVDV calves exhibited prolonged and increased IDV shedding in nasal secretions. An approximate 50% reduction in the thymus was observed in acutely infected BVDV calves (G2) compared to controls (G1). On day 42, thymus depletion was observed in two calves in G4, while three had normal weight. BVDV-2-exposed calves had impaired CD8 T cell proliferation after IDV recall stimulation, and the α/β T cell impairment was particularly evident in those with persistent thymic atrophy. Conversely, no difference in antibody levels against IDV was noted. BVDV-induced thymus depletion varied from transient to persistent. Persistent thymus atrophy was correlated with weaker T cell proliferation, suggesting correlation between persistent thymus atrophy and impaired T cell immune response to subsequent infections. Full article

Antivenom is currently the standard-of-care treatment for snakebite envenoming, but its efficacy is limited by treatment delays, availability, and in many cases, species specificity. Many of the rapidly lethal effects of envenoming are caused by venom-derived toxins, such as phospholipase A2 (sPLA2); therefore, small molecule direct toxin inhibitors targeting these toxins may have utility as initial and adjunct therapies after envenoming. Varespladib (intravenous, IV) and varespladib-methyl (oral) have been shown to potently inhibit sPLA2s from snake venoms in murine and porcine models, thus supporting their further study as potential treatments for snakebite envenoming. In this pilot study, we tested the ability of these compounds to reverse neurotoxic effects of venom from the Australian and Papuan taipan (Oxyuranus scutellatus) subspecies in juvenile pigs (Sus domesticus). The mean survival time for control animals receiving Australian taipan venom (0.03 mg/kg, n = 3) was 331 min ± 15 min; for those receiving Papuan taipan venom (0.15 mg/kg, n = 3) it was 178 ± 31 min. Thirteen pigs received Australian taipan venom and treatment with either IV or oral varespladib (or with IV to oral transition) and all 13 survived the duration of the study (≥96 h). Eight pigs received Papuan taipan venom followed by treatment: Briefly: Two animals received antivenom immediately and survived to the end of the study. Two animals received antivenom treatment delayed 45 min from envenoming and died within 4 h. Two animals received similarly delayed antivenom treatment and were rescued by varespladib. Two animals were treated with varespladib alone after a 45-min delay. Treatment with varespladib only was effective but required repeat dosing over the course of the study. Findings highlight both the importance of early treatment and, as well, a half-life for the investigational inhibitors now in Phase II clinical trials for snakebite. Varespladib rapidly reversed weakness even when administered many hours post-envenoming and, overall, our results suggest that varespladib and varespladib-methyl could be efficacious tools in the treatment of sPLA2-induced weakness from Oxyuranus envenoming. Further clinical study as initial therapy and as potential method of rescue from some types of antivenom-resistant envenomings are supported by these data. Full article