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.

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.
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).
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.
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.

Drug-resistant bacteria are one of the main reasons of deaths worldwide. One of the significant groups of these bacteria are carbapenemase-producing Enterobacteriaceae (CPE). The goal of this cross-sectional study was the identification and hierarchisation of selected risk factors of CPE colonisation. To achieve that goal, we examined 236 patients for the presence of CPE using the standard method of anal swabs. The patients were divided into three groups: hospitalised patients; those chronically dialysed; those requiring home care. A very thorough medical interview was conducted for comorbidities. A statistical analysis relationship between comorbidities and locations of the patient\'s stay with the positive result of the culture was investigated. A significant relationship was demonstrated between the positive result of the culture and confirmed dementia, heart failure, connective tissue diseases, and established irregularities in the level of leukocytes. No significant relationship was demonstrated with the remaining comorbidities considered in the study. Afterwards these factors were compared for importance for the assessment of risk of a positive swab result-the biggest importance was found in establishing connective tissue disease. Next were dementia, abnormal values of leukocytes, heart failure, and at the end, stay at the orthopaedics ward. Conclusions: The study identified asymptomatic carriers of CPE, which demonstrates the need for further studies in order to identify infection risk factors. The connective tissue diseases are the most important variable which enable the prediction of CPE colonisation-the next ones are dementia, abnormal values of leukocytes, heart failure, and stay at the orthopaedics ward.

We assessed non motor characteristics of 12 asymptomatic p.A53T mutation carriers (A53T-AC) compared with 36 healthy controls (HC) enrolled in the Parkinson\'s Progression Markers Initiative (PPMI) study. Olfaction score was lower and anxiety was marginally more prevalent in A53T- AC. These findings suggest distinct prodromal features in this group of subjects.

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.

Asymptomatic SARS-CoV-2-infected individuals are thought to play major roles in virus transmission. This study aimed to analyze the characteristics of asymptomatic carriers with COVID-19 to control the spread of the virus. We retrospectively investigated the clinical characteristics of 648 consecutive subjects who were enrolled in the study and were divided into asymptomatic carriers, mild cases, ordinary cases, severe or critical cases, and evaluated their impact on disease severity by means of Spearman correlation and multiple regression analyses. Receiver operating characteristic curve analysis was conducted to determine the optimum cutoff levels of laboratory findings for diagnostic predictors of asymptomatic carriers of COVID-19. In our study, a total of 648 subjects on admission with a mean age of 45.61 y including 345 males and 303 females were enrolled in our study. The leukocyte, lymphocyte, eosinophil, platelet, C-reactive protein, interleukin-6, CD3+, CD4+, and CD8 + T lymphocyte levels, and the erythrocyte sedimentation rate differed significantly among the groups (all p ≤ 0.05). Disease severity was negatively associated with the CD3+ (r = -0.340; p < 0.001), CD4+ (r = -0.290; p = 0.001) and CD8+ (r = -0.322; p < 0.001) T lymphocyte levels. The significant diagnostic predictors of asymptomatic carriers of COVID-19 included the blood cell, cytokine, and T lymphocyte subset levels. Inflammation and immune response may play important roles in disease progression. Hence, the laboratory parameters identified should be considered in clinical practice, which provide new insights into the identification of asymptomatic individuals and the prevention of virus transmission.

In the present pilot study, massively parallel sequencing (MPS) technology was used to investigate cellular small RNA (sRNA) levels in the peripheral blood mononuclear cells (PBMCs) of human T-lymphotropic virus type I (HTLV-I) infected asymptomatic carriers with monoclonal (ASM) and polyclonal (ASP) T cell receptor (TCR) γ gene. Blood samples from 15 HTLV-I asymptomatic carriers (seven ASM and eight ASP) were tested for the clonal TCR-γ gene and submitted for sRNA library construction together with blood samples of five healthy controls (HCs) using Illumina sequencing platform. The sRNA-sequencing reads were aligned, annotated and profiled using various bioinformatics tools. Based on these results, possible markers were validated in the study samples by performing reverse transcription-quantitative (RT-q)PCR analysis. A total of 76 known sRNAs and 52 putative novel sRNAs were identified. Among them, 44 known and 34 potential novel sRNAs were differentially expressed in the ASM and ASP libraries compared with HCs. In addition, 10 known sRNAs were exclusively dysregulated in the ASM group and one (transfer RNA 65) was significantly upregulated in the ASP group. Homo sapiens (hsa) microRNA (miRNA/mir)-23a-3p, -28-5p, hsa-let-7e-5p and hsa-mir-28-3p and -361-5p were the most abundantly upregulated mature miRNAs and hsa-mir-363-3p, -532-5p, -106a-5p, -25-3p and -30e-5p were significantly downregulated miRNAs (P<0.05) with a >2-fold difference between the ASM and ASP groups compared with HCs. Based on these results, hsa-mir-23a-3p and -363-3p were selected for additional validation. However, the quantification of these two miRNAs using RT-qPCR did not provide any significant differences. While the present study failed to identify predictive sRNA markers to distinguish between ASM and ASP, the MPS results revealed differential sRNA expression profiles in the PBMCs of HTLV-1 asymptomatic carriers (ASM and ASP) compared with HCs.

OBJECTIVE: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting.
METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients\' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination.
RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively.
CONCLUSIONS: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

During the last decade much progress has been made in reducing malaria transmission in Macha, Southern Province, Zambia. Introduction of artemisinin combination therapies as well as mass screenings of asymptomatic carriers is believed to have contributed the most. When an endemic malaria situation is moving towards a non-endemic situation the resident population loses acquired immunity and therefore active case detection and efficient surveillance is crucial to prevent epidemic outbreaks. Our purpose was to evaluate the impact of cell phone surveillance and geographical information systems on malaria control in Macha. Furthermore, it evaluates what screening and treatment of asymptomatic carriers and implementation of rapid diagnostic tests in rural health care has led to. Ten in-depth semi-structured interviews, field observations and data collection were performed at the Macha Research Trust and at surrounding rural health centers. This qualitative method was inspired by rapid assessment procedure. The cell phone surveillance has been easily integrated in health care, and its integration with Geographical Information Systems has provided the ability to follow malaria transmission on a weekly basis. In addition, active case detection of asymptomatic carriers has been fruitful, which is reflected in it soon being applied nationwide. Furthermore, rapid diagnostic tests have provided rural health centers with reliable malaria diagnostics, thereby decreasing excessive malaria treatments and selection for drug resistance. This report reflects the importance of asymptomatic carriers in targeting malaria elimination, as well as development of effective surveillance systems when transmission decreases. Such an approach would be cost-efficient in the long run through positive effects in reduced child mortality and relief in health care.