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Background: Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by amyloid fibril deposition. The TTR c.148G > T mutation (V30L) in ATTR is rarely reported, and its biochemical properties are unknown. Methods: Seven patients and two asymptomatic carriers from two unrelated families diagnosed with V30L variant of ATTR were included. Data on clinical manifestations, laboratory examination, electrophysiology, ophthalmological corneal confocal microscopy (CCM), pathology and molecular biological experiments was collected and analyzed. Results: Most patients initially experienced paresthesia, with varying degrees of peripheral neuropathy, autonomic dysfunction, and cardiac involvement. Nerve conduction studies showed extensive motor and sensory nerve involvement in upper and lower limbs. CCM revealed reduced corneal nerve density and fiber length. Sural nerve biopsies indicated loss of myelinated nerve fibers, with neurogenic patterns in gastrocnemius muscle biopsies. Asymptomatic carriers had nearly normal electrophysiology but mild reductions in corneal nerve fiber density and length. Sural nerve biopsies in carriers showed mild reductions in small myelinated nerve fibers. V30L mutation impaired thermodynamic and kinetic stability of the mutant protein. Plasma TTR tetramer concentration was lower in ATTR V30L patients compared to healthy donors. Small molecule stabilizers failed to exhibit satisfactory inhibition on fibril formation of V30L mutation in vitro. Conclusion: This study highlights the multisystem involvement in ATTR V30L patients, including neuropathy and cardiac issues. Both patients and carriers showed abnormalities in nerve conduction, corneal microscopy, and pathology. The V30L mutation impaired protein stability and reduced plasma TTR tetramer levels. Small molecule stabilizers were ineffective, indicating a need for alternative treatments. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction/Aims Methods Results Discussion It is imperative to screen asymptomatic carriers of transthyretin (TTR) mutations to initiate treatment early. The protocol for repeated electrodiagnostic (EDX) assessments over time lacks standardization. Our aim was to report the electrophysiological evolution of a cohort of asymptomatic carriers and to determine which biomarkers were most sensitive to change.We performed a retrospective review of medical records of asymptomatic carriers identified by screening families with amyloid neuropathy. Carriers who underwent two EDX assessments with a minimum 1‐year interval between studies were selected. EDX included analysis of median, ulnar, tibial, fibular and sural nerves, motor unit number index (MUNIX), electrochemical skin conductance, sympathetic skin response, and heart rate variability on deep breathing. Measurements were compared at first and second examinations.Twenty‐three carriers were included with a median age of 49 years (interquartile range 37–58). Median time between examinations was 3 years (2–4). Compound muscle and sensory nerve action potential (CMAP and SNAP) amplitudes, nerve conduction velocities, autonomic small fiber testing and MUNIX remained stable except for motor distal latency of the median nerve (+0.07 ms/year) and CMAP duration of the ulnar (+0.10 ms/year) and fibular (+0.12 ms/year) nerves. The CMAP duration of the ulnar nerve was the most sensitive biomarker to change when performed within 10 years preceding the age of the youngest case in the family, with a standardized response mean of 0.91.Nerve conduction parameters remain relatively stable in asymptomatic TTR carriers. Changes can only be detected using multimodal and extensive electrophysiological tests. [ABSTRACT FROM AUTHOR]

Based on a systematic review of convolutional neural networks (CNN), this study explores the efficacy of small imaging sensors in monitoring the real-time presence of cyanotoxins and hazardous contaminants in urban ecosystems. To develop a machine learning-based CNN, this study first investigated the relationships between the prevalence of hazardous algal blooms (HABs) and faecal indicator bacteria (FIB) in waterways and aquifers of certain semi-arid zones of Sri Lanka, Sweden and New York (United States). By incorporating a popularly known AbspectroscoPY framework to effectively process the spectrophotometric data of the obtained samples, the formulation subsequently reveals strong positive correlations between FIB coliforms and nutrient loads (particularly nitrate and phosphate). A corroborative association with the incidence of chronic kidney disease of uncertain aetiology (CKDu) among the residents of the studied regions further affirms the reliability of the methodology. These findings underline the need for policymakers to consider the geographical and land-use traits of urban habitats in strategies aimed at reducing water-borne health hazards. [ABSTRACT FROM AUTHOR]

Asymptomatic carriers of Plasmodium falciparum represent important parasite reservoirs maintaining malaria transmission in the community. This study aimed on the one hand to screen the other household members living with children under seasonal malaria chemoprevention (SMC) coverage in order to determine the level of malaria infection in this population and on the other hand to determine the appropriate type of rapid diagnostic test (RDT) for this screening to detect these asymptomatic carriers in the community. During the 2022 SMC campaign (July to October), a cross-sectional survey was carried out in 745 participants who were screened by ultrasensitive rapid diagnostic test (usRDT), standard rapid diagnostic test (rRDT) and microscopy. Out of them, 395 had microscopy results available and were included in the data analysis. The prevalence of asymptomatic carriers of asexual forms of Plasmodium falciparum was 26.58% (105/395) while sexual forms were found in 5.32% (21/395) of the study population. Children from 5 to 15 years had the highest prevalence of P. falciparum asexual forms 35.76% (59/165) compared with older participants. Malaria positivity rate for rRDT and usRDT was 29.40% (219/745) and 40.49% (305/745) respectively. The usRDT had a higher sensitivity than the rRDT (72.38% (95% CI 62.8–80.66) vs. 60.95% (95% CI 50.94–70.33)). In terms of specificity, rRDT had a higher specificity 82.41% (95% CI 77.53–86.62) versus 69.66% (95% CI 64.01–74.89) for usRDT. This study reports a high prevalence of parasite carriers in household members of children under SMC coverage in Nanoro, Burkina Faso. In conclusion, usRDT seems more appropriate for strategies based on detection and treatment of parasite carriers within the community. [ABSTRACT FROM AUTHOR]

Abstract Background Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain. Methods National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected. Results The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group. Conclusions The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.

This study aimed to investigate the SARS-CoV-2 infection prevalence among >18-year-old students in the Faculty of Public Health and Faculty of Sciences at the Lebanese University in Tripoli, Northern Lebanon, in June 2023 and to characterize the circulating Omicron subvariants. Out of 357 participants, only 2 (0.56%) tested positive by qPCR, corresponding to 0.61% (2/326) of asymptomatic students. One case tested positive with a qPCR targeting the Omicron BA.2 variant. These findings indicate a low incidence at that time and emphasize the interest of SARS-CoV-2 surveillance among students. [ABSTRACT FROM AUTHOR]

Lymphatic filariasis is a leading cause of chronic and irreversible damage to human immunity. This paper presents deterministic and continuous-time Markov chain (CTMC) stochastic models regarding lymphatic filariasis dynamics. To account for randomness and uncertainties in dynamics, the CTMC model was formulated based on deterministic model possible events. A deterministic model's outputs suggest that disease extinction is feasible when the secondary threshold infection number is below one, while persistence becomes likely when the opposite holds true. Furthermore, the significant contribution of asymptomatic carriers was identified. Results indicate that persistence is more likely to occur when the infection results from asymptomatic, acutely infected, or infectious mosquitoes. Consequently, the CTMC stochastic model is essential in capturing variabilities, randomness, associated probabilities, and validity across different scales, whereas oversimplification and unpredictability of inherent may not be featured in a deterministic model. [ABSTRACT FROM AUTHOR]

It is acknowledged that dengue infection has a significant economic impact due to healthcare costs and lost productivity. Research can provide insights into the economic burden of the disease, guiding policymakers in their allocation of resources for prevention and control interventions. In this work, we structured a novel mathematical model that describes the spread of dengue with the effects of carriers, an index of memory and vaccination. To show the effect of treatment on the dynamics of dengue, we have incorporated medication-related treatment into the system. The proposed dynamics are represented by using fractional derivatives to capture the role of memory in the control of the infection. We introduced the fundamental principles and notions of non-integer derivatives for the analysis of the model; moreover, the existence and uniqueness results for the solution of the system have been established with the help of mathematical skills. The theory of fixed points has been utilized for the analysis and examination of the system. We have established Ulam-Hyers stability for the recommended system of dengue infection. Regarding the numerical findings, a numerical method is presented to highlight the solution pathways for the system of dengue infection. Several simulations have been performed to visualize the contribution of the input parameters of the system to the prevention and control of the infection. The index of memory, vaccination, and treatment are suggested to be attractive parameters which can reduce the level of infection while the biting rate, asymptomatic carriers and transmission rate are critical as they can increase the risk of the infection in society. Our findings not only provide information for the effective management of the infection they also possess valuable insights that can improve public health.

A significant proportion of malaria infections in humans exhibit no symptoms, but it is a reservoir for maintaining malaria transmission. A time periodic reaction-diffusion model for malaria spread is introduced in this paper, incorporating spatial heterogeneity, incubation periods, symptomatic and asymptomatic carriers. This paper introduces the concept of the basic reproduction number R 0 , which is defined as the spectral radius of the next generation operator, and we present some preliminary results by elementary analysis. The threshold dynamic behavior analysis shows that when R 0 < 1 , the disease is extinct, and when R 0 > 1 , the disease is persistent. We investigate the case of constant system parameters, focusing on the global asymptotic stability of the disease-free steady state when R 0 = 1 . In the numerical simulation section, we validate the theoretical results obtained, and then use elasticity analysis methods to explore the influence of parameters on the output solution. In addition, sensitivity analysis of the basic reproduction number under homogeneous conditions indicates direction of controlling malaria transmission. And several control measures are evaluated in the following steps. [ABSTRACT FROM AUTHOR]

This study presents a mathematical model to investigate the patterns of transmission in lymphatic filariasis. The model considers chronic, acute, and asymptomatic individuals and integrates key control strategies. Random synthetic data is generated robustly through numerical solutions to closely replicate real-world scenarios and encompass uncertainties. The synthetic data adheres to a Gaussian distribution to ensure validity and reliability. Following the derivation of the basic and effective reproduction number using the next generation matrix approach, Latin Hypercube Sampling (LHS) and the Partial Rank Correlation Coefficient (PRCC) algorithm is utilized to assess the parameters that significantly influence the model outputs. The study examine the trajectories of different population compartments through numerical simulations over time, with particular emphasis on the role played by asymptomatic individuals in the transmission of the disease. To assess the potential for disease elimination, the study introduces a range of strategies involving protective measures, treatment interventions, and mosquito control. These strategies are determined through sensitivity analysis. The findings demonstrate that the simultaneous implementation of all control measures has a noteworthy effect in managing lymphatic filariasis. In conclusion, the proposed model enhances understanding of lymphatic filariasis dynamics and informs effective control strategies.

This study aimed to investigate the SARS-CoV-2 infection prevalence among >18-year-old students in the Faculty of Public Health and Faculty of Sciences at the Lebanese University in Tripoli, Northern Lebanon, in June 2023 and to characterize the circulating Omicron subvariants. Out of 357 participants, only 2 (0.56%) tested positive by qPCR, corresponding to 0.61% (2/326) of asymptomatic students. One case tested positive with a qPCR targeting the Omicron BA.2 variant. These findings indicate a low incidence at that time and emphasize the interest of SARS-CoV-2 surveillance among students.

Background: Hepatitis B virus (HBV) infection in India has prevalence of around 40 million chronic HBV (CHB) carriers; 1 to 2 lakhs reported deaths annually due to its complications, such as cirrhosis and hepatocellular carcinoma. Most are asymptomatic, serving as the source of this highly transmissible infection. These patients must be evaluated and monitored regularly, for prediction of their prognosis to reduce their morbidity and mortality. Aims and Objectives: In this study, asymptomatic CHB carriers are evaluated, to assess the risk factors, and to determine replication markers of HBV and coinfection with hepatitis D virus. Materials and Methods: In this cross-sectional study, 123 asymptomatic CHB carriers were subjected to hepatitis B serological assays such as hepatitis B surface antigen, hepatitis B “e” antigen, anti-hepatitis B “e” antibody, and anti-HDV antibody by enzyme-linked immunosorbent assay. Results: Majority (70%) belonged to the age group of 21–50 years. Replicative carriers (HBeAg+) belonging to the age group below 40 years constituted 75% (P=0.04). The most common risk factor in the study group was frequent therapeutic injections (36.6%) followed by family contacts (33.3%). Significant part of family contacts was replicative carrier (P=0.025). Serological profile showed that 83.3% were HBe-seroconverted, with only16.2% showing HBeAg positivity. No patient showed co/super-infection with HDV. Conclusion: Preponderance of hepatitis B carrier status in young adult males and four fold increased incidence in family contacts than general population necessitates stringent screening of young adults and family contacts. Furthermore, this study mandates regular evaluation of chronic hepatitis B carriers by serological assays for better therapeutic management.

It is acknowledged that dengue infection has a significant economic impact due to healthcare costs and lost productivity. Research can provide insights into the economic burden of the disease, guiding policymakers in their allocation of resources for prevention and control interventions. In this work, we structured a novel mathematical model that describes the spread of dengue with the effects of carriers, an index of memory and vaccination. To show the effect of treatment on the dynamics of dengue, we have incorporated medication-related treatment into the system. The proposed dynamics are represented by using fractional derivatives to capture the role of memory in the control of the infection. We introduced the fundamental principles and notions of non-integer derivatives for the analysis of the model; moreover, the existence and uniqueness results for the solution of the system have been established with the help of mathematical skills. The theory of fixed points has been utilized for the analysis and examination of the system. We have established Ulam-Hyers stability for the recommended system of dengue infection. Regarding the numerical findings, a numerical method is presented to highlight the solution pathways for the system of dengue infection. Several simulations have been performed to visualize the contribution of the input parameters of the system to the prevention and control of the infection. The index of memory, vaccination, and treatment are suggested to be attractive parameters which can reduce the level of infection while the biting rate, asymptomatic carriers and transmission rate are critical as they can increase the risk of the infection in society. Our findings not only provide information for the effective management of the infection they also possess valuable insights that can improve public health. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy (LHON) using full-field electroretinography (FERG) and optical coherence tomography (OCT). METHODS: Individuals diagnosed with LHON at the Renmin Hospital of Wuhan University and their family members were included in this cross-sectional observational study. The FERG a-wave amplitude of affected patients and asymptomatic carriers was analyzed. The thickness of the outer nuclear layer (ONL), inner and outer segment (IS/OS) and total photoreceptors in the macular fovea and parafovea were measured. RESULTS: This study included 14 LHON patients (mean age: 20.00±9.37y), 12 asymptomatic carriers (mean age: 39.83±6.48y), and 14 normal subjects (mean age: 24.20±1.52y). The FERG results showed that the dark-adapted 3.0 electroretinography and light-adapted 3.0 electroretinography a-wave amplitudes of patients and carriers were significantly decreased (P0.05). CONCLUSION: Photoreceptors function is significantly impaired in LHON-affected patients and asymptomatic carriers. Meanwhile, photoreceptors morphology is slightly altered, mainly manifesting as a change in ONL thickness.

Abstract Background Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. Methods The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. Results Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29–1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. Conclusion Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite’s enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.

Pneumonia remains a significant global health concern, claiming millions of lives annually. This study introduces a novel approach by developing and analyzing a Caputo fractional order pneumonia infection model that incorporates pneumonia asymptomatic carriers. Through a qualitative lens, we establish the existence and uniqueness of model solutions by applying the well-known Picard–Lindelöf criteria. Employing a next-generation approach, we compute the model's basic reproduction number, determine equilibrium points, and probe their stabilities. The main objective of this study is to investigate the transmission dynamics of pneumonia infection with a focus on asymptomatic carriers using fractional order modeling. Our findings reveal innovative outcomes as we showcase numerical simulations, providing a practical verification of the qualitative results. Notably, we explore the fractional order model solutions in-depth, examining the influence of specific model parameters and fractional orders on the dynamics of pneumonia disease transmission. The significant contributions of this study lie in advancing the theoretical foundation of infectious disease modeling, particularly in the context of pneumonia. Through rigorous analysis and numerical simulations, we provide valuable insights into the behavior of the proposed fractional order model. These findings hold practical implications for understanding and managing pneumonia transmission in real-world scenarios. Our study serves as a vital resource for researchers, policymakers, and healthcare practitioners involved in combating and preventing the spread of pneumonia, ultimately contributing to global efforts in public health.

To describe the clinical phenotype of retinitis pigmentosa (RP) caused by PRPF31-variants and clinical characterization of asymptomatic PRPF31 carriers. We conducted a descriptive cross-sectional deep phenotyping study. We included subjects with PRPF31 variants predicted to be disease-causing, both individuals with RP and asymptomatic carriers. Participants underwent a comprehensive clinical examination of standard visual function parameters (visual acuity, contrast sensitivity, Goldmann visual field), full-field stimulus threshold (FST), full-field electroretinogram (ff-ERG), and a structural investigation with slit lamp and multimodal imaging. We used Spearman correlation analyses to evaluate associations between quantitative outcomes. We included 21 individuals with disease-causing PRPF31-variants: 16 symptomatic and 5 asymptomatic subjects. The symptomatic subjects demonstrated a typical RP phenotype with constricted visual fields, extinguished ff-ERG, and disrupted outer retinal anatomy. FST was impaired and correlated significantly with other outcome measures in RP subjects. Structure–function correlations with Spearman correlation analysis showed moderate correlation coefficients due to a few outliers in each analysis. The asymptomatic individuals had normal best-corrected visual acuity and visual fields, but showed reduced ff-ERG amplitudes, borderline FST sensitivity, and structural abnormalities on OCT and fundoscopy. RP11 has a typical RP phenotype but varies in terms of severity. FST measurements correlated well with other functional and structural metrics and may be a reliable outcome measure in future trials as it is sensitive to a broad range of disease severities. Asymptomatic carriers showed sub-clinical disease manifestations, and our findings underline that reported non-penetrance in PRPF31-related RP is not an all-or-none phenomenon. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection in India has prevalence of around 40 million chronic HBV (CHB) carriers; 1 to 2 lakhs reported deaths annually due to its complications, such as cirrhosis and hepatocellular carcinoma. Most are asymptomatic, serving as the source of this highly transmissible infection. These patients must be evaluated and monitored regularly, for prediction of their prognosis to reduce their morbidity and mortality. Aims and Objectives: In this study, asymptomatic CHB carriers are evaluated, to assess the risk factors, and to determine replication markers of HBV and coinfection with hepatitis D virus. Materials and Methods: In this cross-sectional study, 123 asymptomatic CHB carriers were subjected to hepatitis B serological assays such as hepatitis B surface antigen, hepatitis B "e" antigen, anti-hepatitis B "e" antibody, and anti-HDV antibody by enzyme-linked immunosorbent assay. Results: Majority (70%) belonged to the age group of 21-50 years. Replicative carriers (HBeAg+) belonging to the age group below 40 years constituted 75% (P=0.04). The most common risk factor in the study group was frequent therapeutic injections (36.6%) followed by family contacts (33.3%). Significant part of family contacts was replicative carrier (P=0.025). Serological profile showed that 83.3% were HBe-seroconverted, with only16.2% showing HBeAg positivity. No patient showed co/super-infection with HDV. Conclusion: Preponderance of hepatitis B carrier status in young adult males and four fold increased incidence in family contacts than general population necessitates stringent screening of young adults and family contacts. Furthermore, this study mandates regular evaluation of chronic hepatitis B carriers by serological assays for better therapeutic management. [ABSTRACT FROM AUTHOR]

Abstract Background Adult T-cell Leukemia/Lymphoma (ATLL) is a rapidly progressing type of T-cell non-Hodgkin lymphoma that is developed after the infection by human T-cell leukemia virus type 1 (HTLV-1). It could be categorized into four major subtypes, acute, lymphoma, chronic, and smoldering. These different subtypes have some shared clinical manifestations, and there are no trustworthy biomarkers for diagnosis of them. Methods We applied weighted-gene co-expression network analysis to find the potential gene and miRNA biomarkers for various ATLL subtypes. Afterward, we found reliable miRNA-gene interactions by identifying the experimentally validated-target genes of miRNAs. Results The outcomes disclosed the interactions of miR-29b-2-5p and miR-342-3p with LSAMP in ATLL_acute, miR-575 with UBN2, miR-342-3p with ZNF280B, and miR-342-5p with FOXRED2 in ATLL_chronic, miR-940 and miR-423-3p with C6orf141, miR-940 and miR-1225-3p with CDCP1, and miR-324-3p with COL14A1 in ATLL_smoldering. These miRNA-gene interactions determine the molecular factors involved in the pathogenesis of each ATLL subtype and the unique ones could be considered biomarkers. Conclusion The above-mentioned miRNAs-genes interactions are suggested as diagnostic biomarkers for different ATLL subtypes.

In many regions across the world, hepatitis B virus (HBV) infection is still endemic and the transmission rate is much greater than majority of the known epidemic diseases. Numerous mathematical models (utilizing various differential operators) have been put forth over the past 20 years to understand the transmission mechanism of HBV in various nations and geographical areas. In this manuscript, an epidemic model with various novelties for capturing the dynamic of HBV while utilizing Caputo–Fabrizio fractional differential operator with asymptomatic carriers and vaccination effects is introduced. Initially, the model is formulated by using the ordinary derivative, and afterward, the fractional differential operator is applied to transform the model into arbitrary-ordered derivative. A few basic mathematical properties for the proposed integer-ordered model is presented. The existence of solution to the problem and its uniqueness of the fractional order model are established by transforming the problem into integral equations and then applying the standard results of fixed point theory. For boundedness and positivity of model’ solution is elaborated utilizing the techniques of fractional calculus. It is too much important to validate the theoretical findings through simulations; therefore, the solution curves of the model under consideration are displayed by using the well-known approach called the Mittag-Leffler. To show the behavior of the order of the operator on the dynamics of the disease, various graphical illustrations are presented at the end of the manuscript. By comparing the findings of the present study with the available literature, it is observed that fractional derivative is better to use than integer-order operator for capturing the realistic scenario of the disease.

Background: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. Methods: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. Results: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29–1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. Conclusion: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells. [ABSTRACT FROM AUTHOR]

• We analyzed the functional and structural changes in retinal ganglion cells (RGCs) and their axons in patients affected by Leber's hereditary optic neuropathy (LHON) using photopic negative response (PhNR) and spectral domain optical coherence tomography (SD-OCT). • The functional and structural changes in RGCs and their axons in LHON asymptomatic carriers have also been evaluated. • In addition, affected individuals were divided into subacute, dynamic and chronic phases based on disease duration in order to evaluate the decay in RGCs function and structure. To analyze the functional and structural changes in retinal ganglion cells (RGCs) and their axons that occur during Leber's hereditary optic neuropathy (LHON) using photopic negative response (PhNR) and spectral domain optical coherence tomography (SD-OCT). Individuals diagnosed with LHON and their family members were invited to participate in this cross-sectional study. PhNR and OCT were used. The PhNR amplitude and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were compared among the three groups. In addition, affected individuals were divided into subacute, dynamic and chronic phases based on disease duration in order to evaluate the decay in RGCs function and structure. 73 affected and 30 carriers with a m.11778G > A mutation were included. PhNR amplitude and the thickness of pRNFL significantly decreased in affected individuals and carriers compared to that of the controls (P＜0.001). However, there was no difference between the carriers and the controls (P＞0.05). There was no difference in the PhNR amplitude of different phases (P = 0.464). In the subacute phase, only temporal pRNFL thickness decreased significantly (P＜0.001). PRNFL thickness decreased significantly in dynamic phase (P＜0.001). Temporal pRNFL thickness continued to decrease in the chronic phase (P = 0.042). In the subacute phase, the function of RGCs was severely impaired. Thickness of pRNFL decreased significantly in four quadrants during disease progression. In the chronic phase, pRNFL thickness decreased slightly. Carriers have shown RGCs dysfunction before pathological changes occur, suggesting subclinical abnormalities. [ABSTRACT FROM AUTHOR]

Introduction: Leishmaniasis is a major health problem and its diagnosis still represents a challenge. Since consistent evidence on the comparison of serological methods is lacking, our work aims to compare five serological tests for the diagnosis of visceral and asymptomatic leishmaniasis in southern France, a region where leishmaniasis is endemic. Methodology: Serum samples from 75 patients living in Nice, France were retrospectively analyzed. They included patients affected by visceral leishmaniasis (VL; n = 25), asymptomatic carriers (AC; n = 25) and negative controls (n = 25). Each sample was tested using two immunochromatographic tests (ICT; IT LEISH® and TruQuick IgG/IgM®), an indirect fluorescent antibody test (IFAT) and two Western Blotting (WB; LDBio BIORAD® and an in-house method). Results: Diagnosis of VL with IFAT and TruQuick® showed the highest diagnostic performance parameters. IFAT had 100% sensitivity and specificity, while TruQuick had 96% sensitivity and 100% specificity. Finally, the two tests showed high accuracy (100% for IFAT and 98% for TruQuick) for the AC group. WB LDBio® was the only method able to detect Leishmania latent infection, with a sensitivity of 92%, and a specificity of 100%, with a Negative Predictive Value (NPV) of 93%. This performance is reflected in the high accuracy of the test. Conclusions: The data obtained with TruQuick® supports its application in the rapid diagnosis of leishmaniasis in endemic areas, a feature not shown by IFAT despite its high diagnostic performance. Regarding the diagnosis of asymptomatic leishmaniasis, the best results were obtained with WB LDBio®, confirming previous studies. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to determine knowledge, attitudes, and practices toward the prevention of typhoid fever among patients aged 15-50 years in Adjumani General Hospital, Adjumani District. Methodology: The study employed a cross-sectional study design with both quantitative approaches. Simple random sampling was used. Data were analyzed manually by use of tally sheets and were entered in the Excel computer program to generate tables, graphs, and pie charts. Results: The study findings revealed that the overall knowledge of the prevention of typhoid fever among the respondents was generally poor, as most (60%) of the respondents did not know anything about typhoid fever. Regarding attitude, the majority (70%) of the respondents agreed washing hands with soap helped in preventing typhoid fever, most (60%) agreed that boiling water also helped in preventing typhoid fever, and the majority (84%) were willing to prevent typhoid fever. In regards to practices half (50%) of the respondents did not know any of the practices that helped in the prevention of typhoid fever, more than half (56%) agreed washing hands with soap helped to minimize typhoid fever infection, the majority (70%) of the agreed on using pit latrine as a fecal disposal facility to minimize typhoid fever infection. Conclusion: The general knowledge, attitude, and practices of the respondents towards the prevention of typhoid fever were generally poor which in the end could lead to an increase in the spread of typhoid fever within the district. Recommendation: Health workers in Adjumani General Hospital should promote community health-based programs to teach the community the best practices to curb the increasing typhoid fever.

At the peak of the COVID-19 pandemic, pooled surveillance strategies were employed to alleviate the overwhelming demand for clinical testing facilities. A major drawback of most pooled-testing methods is the dilution of positive samples, which leads to a loss of detection sensitivity and the potential for false negatives. We developed a novel pooling strategy that compensates for the initial dilution with an appropriate concentration during nucleic acid extraction and real-time PCR. We demonstrated the proof of principle using laboratory-created 10-sample pools with one positive and corresponding individual positive samples by spiking a known amount of heat-inactivated SARS-CoV-2 into viral transport medium (VTM) or pooled negative saliva. No Ct difference was observed between a 10-sample pool with one positive vs. the corresponding individually analyzed positive sample by this method, suggesting that there is no detectable loss of sensitivity. We further validated this approach by using nasopharyngeal swab (NPS) specimens and showed that there is no loss of sensitivity. Serial dilutions of the virus were spiked into VTM and pooled with negative saliva in simulated 10-sample pools containing one positive to determine the LOD and process efficiency of this pooling methodology. The LOD of this approach was 10 copies/PCR, and the process efficiencies are ~95%−103% for N1 and ~87%−98% for N2 with samples in different matrices and with two different master mixes tested. Relative to TaqPath 1-step master mix, the TaqMan Fast Virus 1-Step master mix showed better sensitivity for the N2 assay, while the N1 assay showed no Ct difference. Our pooled testing strategy can facilitate large-scale, cost-effective SARS-CoV-2 surveillance screening and maintain the same level of sensitivity when analyzed individually or in a pool. This approach is highly relevant for public health surveillance efforts aimed at mitigating SARS-CoV-2 spread.

Asymptomatic carriers serve as a potential source of transmission of epidemic diseases. Exposed people who develop symptoms only get tested and remain isolated in their homes or sometimes in hospitals when needed. In contrast, the asymptomatic individuals go untested and spread the disease silently as they roam freely throughout their entire infectious lifetime. The work intends to explore the role of asymptomatic carriers in the transmission of epidemic diseases and investigate suitable optimal control strategies. We propose a SEIAQR compartmental model subdividing the total population into six different compartments. To illustrate the model’s implication, we estimate the number of asymptomatic individuals using COVID-19 data during June 9–July 18, 2021 from Bangladesh. We then analyze the model to explore whether the epidemic subsides if the asymptomatic individuals are tested randomly and isolated. Finally, to gain a better understanding of the potential of this unidentified transmission route, we propose an optimal control model considering two different control strategies: personal protective measures and isolation of asymptomatic carriers through random testing. Our results show that simultaneous implementation of both control strategies can reduce the epidemic early. Most importantly, sustained effort in identifying and isolation of asymptotic individuals allows relaxation in personal protective measures.

Background: Adult T-cell Leukemia/Lymphoma (ATLL) is a rapidly progressing type of T-cell non-Hodgkin lymphoma that is developed after the infection by human T-cell leukemia virus type 1 (HTLV-1). It could be categorized into four major subtypes, acute, lymphoma, chronic, and smoldering. These different subtypes have some shared clinical manifestations, and there are no trustworthy biomarkers for diagnosis of them. Methods: We applied weighted-gene co-expression network analysis to find the potential gene and miRNA biomarkers for various ATLL subtypes. Afterward, we found reliable miRNA-gene interactions by identifying the experimentally validated-target genes of miRNAs. Results: The outcomes disclosed the interactions of miR-29b-2-5p and miR-342-3p with LSAMP in ATLL_acute, miR-575 with UBN2, miR-342-3p with ZNF280B, and miR-342-5p with FOXRED2 in ATLL_chronic, miR-940 and miR-423-3p with C6orf141, miR-940 and miR-1225-3p with CDCP1, and miR-324-3p with COL14A1 in ATLL_smoldering. These miRNA-gene interactions determine the molecular factors involved in the pathogenesis of each ATLL subtype and the unique ones could be considered biomarkers. Conclusion: The above-mentioned miRNAs-genes interactions are suggested as diagnostic biomarkers for different ATLL subtypes. [ABSTRACT FROM AUTHOR]

This paper mainly concerns about the traveling wave solution (TWS) for a discrete diffusive epidemic model with asymptomatic carriers. Analysis of the model shows that the minimum wave speed c ∗ exists if a threshold ℜ is greater than one. With the help of sub- and super-solutions, we find that the condition for the existence of TWS is ℜ > 1 and wave speed c > c ∗ . Further, we prove that the TWS connects two different boundary steady states. Through the arguments with Laplace transform, we show there is no TWS for the model if ℜ > 1 and 0 < c < c ∗ or ℜ ≤ 1. [ABSTRACT FROM AUTHOR]

Abstract Background Adult T-cell Leukemia/Lymphoma (ATLL) is a cancer disease that is developed due to the infection by human T-cell leukemia virus type 1. It can be classified into four main subtypes including, acute, chronic, smoldering, and lymphoma. Despite the clinical manifestations, there are no reliable diagnostic biomarkers for the classification of these subtypes. Methods Herein, we employed a machine learning approach, namely, Support Vector Machine-Recursive Feature Elimination with Cross-Validation (SVM-RFECV) to classify the different ATLL subtypes from Asymptomatic Carriers (ACs). The expression values of multiple mRNAs and miRNAs were used as the features. Afterward, the reliable miRNA-mRNA interactions for each subtype were identified through exploring the experimentally validated-target genes of miRNAs. Results The results revealed that miR-21 and its interactions with DAAM1 and E2F2 in acute, SMAD7 in chronic, MYEF2 and PARP1 in smoldering subtypes could significantly classify the diverse subtypes. Conclusions Considering the high accuracy of the constructed model, the identified mRNAs and miRNA are proposed as the potential therapeutic targets and the prognostic biomarkers for various ATLL subtypes.

Humans and animals can become asymptomatic carriers of Listeria monocytogenes and introduce the pathogen into their environment with their feces. In turn, this environmental contamination can become the source of food- and feed-borne illnesses in humans and animals, with the food production chain representing a continuum between the farm environment and human populations that are susceptible to listeriosis. Here, we update a review from 2012 and summarize the current knowledge on the asymptomatic carrier statuses in humans and animals. The data on fecal shedding by species with an impact on the food chain are summarized, and the ways by which asymptomatic carriers contribute to the risk of listeriosis in humans and animals are reviewed. [ABSTRACT FROM AUTHOR]

Context: The novel coronavirus disease 2019 (COVID-19) that has emerged as a pandemic now has put health care workers (HCWs) at great risk as they are the warriors in frontlines screening and treating the infected patients. When a COVID-19-positive HCW is identified, its contacts need to be traced to check the spread of the infection among patients and other HCWs. Aims: This study was aimed to study epidemiology and risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection among HCWs and to quantify the risk of infection among HCWs in a tertiary level health care setting. Settings and Design: This cross-sectional study enrolled all the HCWs who were exposed to a patient with COVID-19 in a tertiary level health care center, Rishikesh, Uttarakhand from 1st May to 30th July, 2020. Methods and Material: All the exposed HCWs were followed up for 14 days after the last exposure to a patient with confirmed COVID-19 infection. Epidemiological data were obtained using structured interviews. Statistical Analysis Used: The data were analyzed using SPSS 23.0. Frequencies and proportions were calculated for descriptive variables, and risk ratios were calculated for risk factors affecting the transmission of disease. Results: We observed that 1,141 HCWs of the tertiary level health care hospital were exposed to COVID-19 patients during the study period. A total of 22 HCWs were tested COVID-19 positive among these exposed HCWs. Univariate analysis revealed a high risk of exposure to be significantly associated with a higher secondary attack rate of SARS CoV-2. Conclusions: The study demonstrates the risk of COVID-19 transmission through asymptomatic carriers. Therefore, periodic testing of all health care workers is necessary to ensure early mitigation of the shortage of health care providers.

A mathematical model is developed to predict the optimum level of measures required to control a two-strain typhoid infection. The model considers symptomatic individuals and carriers together with environmental bacteria with different sensitivities to antimicrobials. Treatment for symptomatic individuals in each strain and use of sanitation and proper hygiene practices are considered as control measures. Our simulation results show that combining the three control interventions highly influenced the number of symptomatic individuals and environmental bacteria in both the strains. However, there are still a significant number of asymptomatic carriers in both the strains. This result shows that combating a two-strain typhoid infection requires some control interventions that reduce the number of asymptomatic carriers to near zero, along with optimal treatment combined with proper hygiene/sanitation practices. Further, efficiency analysis is used to investigate the impact of each control strategy on reducing the number of infected individuals and bacteria in both the strains. The study result suggests that implementing the combination of all the three control interventions is the most effective control strategy. [ABSTRACT FROM AUTHOR]

Introduction. Human papillomavirus 13 (HPV-13) belonging to Alphapapillomavirus-10 species, is an oral mucosotropic virus phylogenetically related to other human papillomavirus (6, 11, 44, 55 and 74). It causes Multifocal Epithelial Hyperplasia, an uncommon benign oral disease reported mainly amongst ethnic groups from America. Objective. To describe the genetic variability of the HPV-13 L1 gene. Material and Methods. A retrospective study including 50 oral samples from patients with Multifocal Epithelial Hyperplasia, and 25 samples from asymptomatic carriers of HPV-13, all subjects living in Mayan area of Mexico. A fragment 240 bp corresponding to the HPV 13L1 gene, which encodes the major capsid protein was amplified, sequenced, and compared with the only two reference sequences of HPV-13 available. A phylogenetic tree was constructed using PAUP* software. Results. Eight single nucleotide polymorphisms were identified including three synonymous polymorphism and five non-synonymous. According to the phylogenetic tree, the variants were grouped in two branches. Conclusion. This is the first report for the presence of genetic polymorphisms of HPV-13. These results are relevant for future research aiming to identify lineages and sub lineages. Our in-silico analysis suggests that the amino acid changes would be involving structures directly related to antigen recognition, which requires further investigations. [ABSTRACT FROM AUTHOR]

Context: The novel coronavirus disease 2019 (COVID-19) that has emerged as a pandemic now has put health care workers (HCWs) at great risk as they are the warriors in frontlines screening and treating the infected patients. When a COVID-19-positive HCW is identified, its contacts need to be traced to check the spread of the infection among patients and other HCWs. Aims: This study was aimed to study epidemiology and risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection among HCWs and to quantify the risk of infection among HCWs in a tertiary level health care setting. Settings and Design: This cross-sectional study enrolled all the HCWs who were exposed to a patient with COVID-19 in a tertiary level health care center, Rishikesh, Uttarakhand from 1st May to 30th July, 2020. Methods and Material: All the exposed HCWs were followed up for 14 days after the last exposure to a patient with confirmed COVID-19 infection. Epidemiological data were obtained using structured interviews. Statistical Analysis Used: The data were analyzed using SPSS 23.0. Frequencies and proportions were calculated for descriptive variables, and risk ratios were calculated for risk factors affecting the transmission of disease. Results: We observed that 1,141 HCWs of the tertiary level health care hospital were exposed to COVID-19 patients during the study period. A total of 22 HCWs were tested COVID-19 positive among these exposed HCWs. Univariate analysis revealed a high risk of exposure to be significantly associated with a higher secondary attack rate of SARS CoV-2. Conclusions: The study demonstrates the risk of COVID-19 transmission through asymptomatic carriers. Therefore, periodic testing of all health care workers is necessary to ensure early mitigation of the shortage of health care providers. [ABSTRACT FROM AUTHOR]

Asymptomatic carriers play an important role in modelling infectious diseases. Asymptomatic infected people have no symptoms but can infect other people and spread the disease among other people. The laboratory confirmed that asymptomatic hepatitis B may infect individuals and may generate other infected cases. Due to this significant role of asymptomatic carriers, we are considering a new mathematical model for hepatitis B virus with asymptomatic carriers to study its dynamic analysis. First, we briefly discussed the formulation of the model, and then used the Caputo derivative to generalize the model. Using the definition of fractional stability analysis, we study the results of the model, and show that the model is locally asymptotically stable for disease-free cases when R01, which demonstrates the existence of a unique endemic equilibrium. Additionally, we use a new numerical scheme that is introduced for fractional differential equations to get numerical results. We use a number of fractional order values and present the graphical results of the model.

Background: Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. Methods: We enrolled 193 SARS-CoV-2 infected subjects in Ningbo and Zhoushan, Zhejiang, China, from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and IgG against SARS-CoV-2 using colloidal gold-labeled and enzyme-linked immunosorbent assays. Results: Of those, 31 were asymptomatic SARS-CoV-2 carriers, 148 symptomatic COVID-19 patients, and 14 presymptomatic COVID-19 patients. Compared to symptomatic COVID-19 patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower level of C-reactive protein, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (7.5 vs. 25.5 days, P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic patients than presymptomatic patients (P = 0.003) and asymptomatic carriers (P = 0.004). Viral shedding duration was longer in presymptomatic COVID-19 patients than in asymptomatic carriers (48.0 vs. 24.0 days, P = 0.002). Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89.0% vs. 61.0%, P = 0.028). In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with comorbidities. Conclusion: Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity should be contributable to innate and adaptive cellular immunity rather than humoral immunity. The severity of COVID-19 is associated with older age and comorbidities in familial clustering cases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), ranging from asymptomatic conditions to severe/fatal lung injury and multi-organ failure. Growing evidence shows that the nasopharyngeal microbiota composition may predict the severity of respiratory infections and may play a role in the protection from viral entry and the regulation of the immune response to the infection. In the present study, we have characterized the nasopharyngeal bacterial microbiota (BNM) composition and have performed factor analysis in a group of 54 asymptomatic/paucisymptomatic subjects who tested positive for nasopharyngeal swab SARS-CoV-2 RNA and/or showed anti-RBD-IgG positive serology at the enrolment. We investigated whether BNM was associated with SARSCoV-2 RNA positivity and serum anti-RBD-IgG antibody development/maintenance 20-28 weeks after the enrolment. Shannon's entropy a-diversity index [odds ratio (OR) = 5.75, p = 0.0107] and the BNM Factor1 (OR = 2.64, p = 0.0370) were positively associated with serum anti-RBD-IgG antibody maintenance. The present results suggest that BNM composition may influence the immunological memory against SARS-CoV-2 infections. To the best of our knowledge, this is the first study investigating the link between BNM and specific IgG antibody maintenance. Further studies are needed to unveil the mechanisms through which the BNM influences the adaptive immune response against viral infections. [ABSTRACT FROM AUTHOR]

A deterministic nonlinear mathematical model is developed for typhoid transmission dynamics in human hosts, coupled with multiple transmission routes. The model aims to examine the role of control interventions such as vaccination, environmental sanitation, and saturated treatment on the prevalence of typhoid. First, the qualitative analysis of the model with constant control interventions is performed. The model exhibits a backward bifurcation phenomenon. Sensitivity analysis is also conducted to identify impactful parameters for effective control of the disease. Then, the model is extended to a corresponding optimal control problem to investigate the optimum intervention strategies by assessing their effects on typhoid prevalence and economic load. The characterization of the optimal controls is determined using Pontryagin's Maximum Principle, and the optimality system is developed. Numerical results suggest that, in the absence of treatment, the combination of vaccination and environmental sanitation controls plays an important role in reducing the typhoid burden and economic load. Moreover, the comprehensive use of the three control interventions is more effective than using any single or two combined control interventions. It reduces the number of infective humans and environmental bacteria as well as the cost burden associated with applied controls and opportunity loss. Thus, the comprehensive effect of the three control interventions is found to be more economical during typhoid outbreaks. [ABSTRACT FROM AUTHOR]

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: There is a need for biomarkers to monitor the earliest phases of Parkinson's disease (PD), especially in premotor stages. Here, we studied whether there are early gait alterations in carriers of the G2019S mutation of LRRK2 that can be detected by means of an inertial sensor system.Methods: Twenty-one idiopathic PD patients, 20 LRRK2-G2019S PD, 27 asymptomatic carriers of LRRK2-G2019S mutation (AsG2019S) and 36 controls walked equipped with 16 lightweight inertial sensors in three different experiments: i/normal gait, ii/fast gait and iii/dual-task gait. In the AsG2019S group, DaT-SPECT (123I-ioflupane) with semi-quantitative analysis was carried out. Motor and cognitive performance were evaluated using MDS-UPDRS-III and MoCA scales. We employed neural network techniques to classify individuals based on their walking patterns.Results: PD patients and controls showed differences in speed, stride length and arm swing amplitude, variability and asymmetry in all three tasks (p < 0.01). In the AsG2019S group, the only differences were detected during fast walking, with greater step time on the non-dominant side (p < 0.05), lower step/stride time variability (p < 0.01) and lower step time asymmetry (p < 0.01). DaT uptake showed a significant correlation with step time during fast walking on the non-dominant side (r = -0.52; p < 0.01). The neural network was able to differentiate between AsG2019S and healthy controls with an accuracy rate of 82.5%.Conclusion: Our sensor-based analysis did not detect substantial and robust changes in the gait of LRRK2-G2019S asymptomatic mutation carriers. Nonetheless, step or stride time during fast walking, supported by the observed correlation with striatal DaT binding deserves consideration as a potential biomarker in future studies. [ABSTRACT FROM AUTHOR]

The understanding of coronavirus disease 2019 (COVID-19) is evolving periodically. There is also a marked increase in COVID-19 patients’ demand for the provision of COVID-19 convalescent plasma (CCP) therapy. With the review of the literature, the stage of speculation is quickly moving towards conformity, with the interim guidelines given by the Food and Drug Administration (FDA) in the United States, United Kingdom’s blood transfusion services, Saudi’s FDA, and the Indian Council for Medical Research, in addition to the European health authorities. It is prudent to address the ethical concerns that merit consideration while harvesting and utilizing CCP as a therapeutic tool in local hospital setting.

Abstract The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost–benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), ranging from asymptomatic conditions to severe/fatal lung injury and multi-organ failure. Growing evidence shows that the nasopharyngeal microbiota composition may predict the severity of respiratory infections and may play a role in the protection from viral entry and the regulation of the immune response to the infection. In the present study, we have characterized the nasopharyngeal bacterial microbiota (BNM) composition and have performed factor analysis in a group of 54 asymptomatic/paucisymptomatic subjects who tested positive for nasopharyngeal swab SARS-CoV-2 RNA and/or showed anti-RBD-IgG positive serology at the enrolment. We investigated whether BNM was associated with SARS-CoV-2 RNA positivity and serum anti-RBD-IgG antibody development/maintenance 20–28 weeks after the enrolment. Shannon’s entropy α-diversity index [odds ratio (OR) = 5.75, p = 0.0107] and the BNM Factor1 (OR = 2.64, p = 0.0370) were positively associated with serum anti-RBD-IgG antibody maintenance. The present results suggest that BNM composition may influence the immunological memory against SARS-CoV-2 infections. To the best of our knowledge, this is the first study investigating the link between BNM and specific IgG antibody maintenance. Further studies are needed to unveil the mechanisms through which the BNM influences the adaptive immune response against viral infections.

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19.

Abstract Background Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

Relevance. Pandemic of the new coronavirus infection has become a challenging issue for world healthcare system. Control of the epidemic process is one of the main priorities in combat against new coronavirus disease Aim. The research highlights the issue of asymptomatic carriers of the new coronavirus disease. Conclusions. It was revealed that patients with asymptomatic form of COVID-19 have a less lasting immunity response compared with those that have had clinically active forms of the infection. In order to determine pathogenetic process and fully understand formation of the immune response, it is necessary to study both humoral and cellular immune responses in patients diagnosed with COVID-19. In order to select most optimal anti-epidemic measures to contain the further spread of the disease, including asymptomatic carriage, it is necessary to establish SARS-CoV-2 reproduction index and determine minimal infective dose of SARS-CoV-2.

Background: Adult T-cell Leukemia/Lymphoma (ATLL) is a cancer disease that is developed due to the infection by human T-cell leukemia virus type 1. It can be classified into four main subtypes including, acute, chronic, smoldering, and lymphoma. Despite the clinical manifestations, there are no reliable diagnostic biomarkers for the classification of these subtypes.Methods: Herein, we employed a machine learning approach, namely, Support Vector Machine-Recursive Feature Elimination with Cross-Validation (SVM-RFECV) to classify the different ATLL subtypes from Asymptomatic Carriers (ACs). The expression values of multiple mRNAs and miRNAs were used as the features. Afterward, the reliable miRNA-mRNA interactions for each subtype were identified through exploring the experimentally validated-target genes of miRNAs.Results: The results revealed that miR-21 and its interactions with DAAM1 and E2F2 in acute, SMAD7 in chronic, MYEF2 and PARP1 in smoldering subtypes could significantly classify the diverse subtypes.Conclusions: Considering the high accuracy of the constructed model, the identified mRNAs and miRNA are proposed as the potential therapeutic targets and the prognostic biomarkers for various ATLL subtypes. [ABSTRACT FROM AUTHOR]