Clinical Sample Of Patients Research Articles

Bioinformatics Analysis and Spatiotemporal Distribution of the fliC Gene and Its Protein Isolated from Escherichia coli-Infected Patients in Eastern Algeria.

The fliC locus in Escherichia coli primarily encodes flagellar (H) antigens. Exploring fliC sequence diversity will shed light on the mechanisms of bacterial pathogenicity. This study examined the presence of fliC mutant strains of E. coli in infected patients from different age groups, sexes and sample types in eastern Algerian provinces over a span of 2 years. This retrospective, cross-sectional study involved three provinces in eastern Algeria: i) Bordj Bou Arreridj, ii) Setif and iii) Batna. A total of 75 E. coli isolates were obtained from the University State Hospital Centre. Two types of analyses were conducted: i) a bioinformatics analysis of the protein sequences translated from the fliC genes, specifically the fliC flagellar sequences and ii) a multifactorial statistical analysis (multiple correspondence analysis [MCA]) of the population of infected patients, considering various parameters. The fliC protein sequences were aligned using the Multiple Alignment using Fast Fourier Transform (MAFFT) programme. The alignment results were then visualised using the MView programme. Finally, a phylogenetic tree was constructed using the maximum likelihood algorithm in MEGA 11 software. Bioinformatics analysis highlighted the strong conservation of the structures of the fliC protein sequences, especially at the two N- and C-terminal ends, and strong variability in the central zone. This remarkable fliC intersequence similarity is corroborated by the presence of protein motifs identified in the PROSITE protein motif database. fliC mutations in E. coli were not detected in the clinical samples of patients from hospitals in the three Algerian Provinces. Our analysis revealed that all the samples exhibited characteristics of wild-type virulent bacteria without mutations. A multicentre study is warranted for epidemiological surveillance of fliC mutant strains for future preventive measures.

Forget About Memory: Disentangling the Amnestic Syndrome in Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) can present with both episodic amnestic syndrome and biomarkers of Alzheimer's disease (AD) pathology. To examine the associations between amnestic syndrome and cerebrospinal fluid (CSF) AD biomarkers in iNPH and the CSF tap test response in iNPH patients with amnestic syndrome. We used the Free and Cued Selective Reminding Test to divide iNPH into amnestic and non-amnestic patients. We compared their clinical, biological, and radiological characteristics and examined the reversibility of gait spatiotemporal parameters and neuropsychological performances after a CSF tap test. Univariate and multiple linear regression models examined the association between memory performance and clinical-biological characteristics. Sixty-two non-amnestic patients (mean age 77.0±7.0 years, 38.7% female) and thirty-eight amnestic patients (mean age 77.0±5.9 years, 36.8% female) presented similar levels of AD biomarkers and clinical-radiological profiles. Global cognition and education levels were lower in the amnestic iNPH group. We found no association between AD biomarkers and memory performances (total tau: β= -4.50; 95% CI [-11.96;2.96]; p = 0.236; amyloid-β (1-42): β= 8.60, 95% CI [-6.30;23.50]; p = 0.240). At baseline, amnestic iNPH patients performed worse on executive functions, attention, and gait speed but improved similarly to the non-amnestic iNPH patients after the tap test. In our clinical sample of iNPH patients, we confirm the lack of specificity of the amnestic profile for predicting AD pathology. Clinicians should not preclude amnestic iNPH patients from undergoing an invasive procedure of CSF derivation.

Immune triggers preceding neuralgic amyotrophy.

Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown. This was a multicentre, prospective, observational, matched case-control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella-zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection. Fifty-seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43). Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis.

B-302 Therapeutic Drug Monitoring (TDM) of Hydroxychloroquine in Whole Blood: Analysis of Over 10,000 Patient Results

Abstract Background Hydroxychloroquine (HCQ), a mainstay of systemic lupus erythematosus (SLE) therapy, improves survival and reduces flares. Therapeutic drug monitoring (TDM) may be useful in 1) identifying and improving adherence issues, 2) titrating daily dose to achieve therapeutic benefits while 3) minimizing retinopathy due to longterm cumulative exposure. Whole blood (WB) is the correct specimen for HCQ TDM because WB HCQ levels are higher than serum or plasma levels, more stable and reflective of the last month of HCQ ingestion, and are better correlated to efficacy and retinopathy risk. Here, we report WB HCQ concentrations in 10,463 clinical patient samples and their distribution. Methods HCQ concentrations in whole blood are measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and reported in nanograms per milliliters whole blood. Recommended sample collection is ∼ 3 - 6 months into regular stable dosing to reach pharmacokinetic steady state and correlate with clinical efficacy. Results Here, we report the analysis of 10,463 patient samples for whole blood hydroxychloroquine (WB HCQ) concentrations. More than one-third (3752, 35.9%) were within the target range of > 1000 and < 2000 ng/mL. About one-quarter (2568, 24.5%) were within a tighter therapeutic target window, 1000 to 1500 ng/mL. The vast majority (9852, 94.2%,) of all WB HCQ were < 2000 ng/mL with a small percentage >2000 ng/mL (611, 5.8% between 2000 - 9502 ng/mL). About one-third (31.3%) were higher than 1177 ng/mL which corresponds to higher retinopathy risk. Adherence issues were evident in 10.5% (1102) with undetectable (483, 4.6%) and very low (<200 ng/mL) drug (619, 5.9%) (yellow). Depending upon the target threshold, levels < 500 ng/mL or <1000 ng/mL may be considered subtherapeutic as seen in 2498 (23.9%) and 4263 (40.7%) samples, respectively. Conclusions Due to wide pharmacokinetic variability and adherence issues, a given prescribed dose of HCQ does not correspond to WB HCQ, e.g. following 4, 5 or 6 mg/kg/day, levels are known to vary widely from subtherapeutic <500 to >2000 ng/mL. Here, our clinical database reiterates this wide range in WB HCQ levels from undetectable (<25) to 9502 ng/mL in 10,463 patient samples. One-quarter or one-third were within the therapeutic target range of 1000-1500 or 1000-200 ng/mL where >1000 has been associated with better disease control and survival. At the same time, levels less than 1177 avoid higher retinopathy risk. A small percentage of samples, 5.8%, were higher than 2000 ng/mL, suggesting the usefulness in TDM to fine-tune daily dose. In 10%, there was evidence of poor adherence, with very low or no detectable drug, and one quarter to 40% were subtherapeutic (<500 or <1000). The potential benefits of HCQ are many and include reduced flares and improved lupus nephritis, thrombosis risk, and long-term survival. At the same time, prescribed dose does not predict therapeutic levels. TDM-based counseling and dose adjustment may be instrumental in optimizing HCQ benefits while minimizing retinopathy risk. In conclusion, our analysis demonstrates the growing use of whole blood HCQ TDM to facilitate dose titration to safe and most effective target levels.

B-102 The Impact of Protein / Protein Interactions on Serum Free Light Chain Assay Calibration

Abstract Background Since 2001, Serum Free Light Chain measurements have become established as routine clinical laboratory tests. Katzmann (2002) published a reference interval based on 282 normal samples establishing a ratio reference range 0.26-1.65. Whilst kappa and lambda measurements are of little diagnostic value, kappa/lambda ratio gives a strong indication of monoclonal gammopathy. In recent years, it has been suggested that the ratio may have changed. Here we present investigations identifying protein/protein interactions that may account for the discrepancies between QC release and real-world data; identifying a remediation step which will allow verification of the published ratio. Methods The manufacturers QC release data was reviewed for kappa, lambda and kappa/lambda ratio for all lots from 2018-2023, and compared to published data. To mimic field observation, an accelerated stability study was performed on standard calibrators and protein/protein interactions identified using western blot. Subsequently, calibrators were depleted of alpha-1 antitrypsin (A1AT) and other serum proteins using specific affinity chromatography; accelerated stability was repeated. A calibrator of pure polyclonal free light chains (FLC) in human serum albumin was produced in the presence/absence of A1AT and additional interfering serum proteins. Results At release, the average kappa reference range was 7.2-29.5 mg/L (62 kits, 9 different US blood donor sera collections and 3852 data points) and 7.7-24 mg/L for lambda (78 kits, 9 different US blood donor sera and 4664 data points), with a kappa/lambda ratio of 0.45-1.69. There was minimal change over 5yrs to these measurements. Analysis of FLC calibrators during an accelerated stability identified interactions between kappa FLC and ubiquitous serum proteins, including A1AT. The standard calibrator activity declined by 14.9±0.1% (mean±SEM) over a 4-month accelerated period @22oC, equivalent to 16 months real time. Calibrators depleted of A1AT and specific additional serum proteins showed significantly less decline in activity 1.4±1.4%, p<0.001. When blood donor sera were analysed using the standard calibrators following 4 months at 22oC, the results showed an increase in the reported kappa concentrations compared to those generated from frozen calibrators (19.0[15.4-22.5] to 21.3[17.0-26.0] mg/L, 12.5±3.8%, p<0.001). This observation was mirrored in kappa/lambda ratio (1.3[1.1-1.5] to 1.4[1.2-1.7] mg/L, 12.5±3.8%, p<0.001) and when clinical patient samples were assessed (30.1[14.0-47.1] to 34.3[15.5-56.9] mg/L, 13.8±1.4%, p<0.001). The depleted calibrator did not report an increase in sample results. FLC+HSA calibrators, when spiked with either physiological concentrations of A1AT or other serum proteins, showed a 16.7% and 15.3% decrease in activity respectively, compared to FLC+HSA calibrators without additional proteins. Conclusions At release, US blood donor sera have different absolute kappa mg/L compared to the published reference interval, but these changes do not invalidate the published kappa/lambda ratio, in contrast to recent reports and have not changed since 2018. An unpredictable kappa/protein interaction was observed, particularly with A1AT in a time dependent fashion, which correlated to a reduction in calibrator activity. Removal of A1AT and other specific serum proteins remediated the issue, and the kappa/lambda ratio was verified irrespective of the age of the calibrator.

Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma.

Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

When sexual distress shares the bed: the role of sexual self-esteem in the relationship between dispositional mindfulness and sexual distress in sex therapy patients.

Sexual distress (eg, feeling distressed, unhappy, frustrated, stressed, dissatisfied, or bothered about their sexuality) is a central concern reported by patients seeking sex therapy, and might be related to sexual self-esteem and mindfulness disposition, yet research is needed to examine the links among those variables within the specific population of patients seeking therapy. This study aimed to examine the indirect role of sexual self-esteem in the relationship between dispositional mindfulness and sexual distress. The study was conducted among 696 patients undergoing sexual therapy (mean age 34.19 ± 11.21 years, age range 18-78years). Participants identified as women (57.3%), men (38.5%), or nonbinary (4.2%). They completed self-report questionnaires assessing dispositional mindfulness (Five Facet Mindfulness Questionnaire), sexual self-esteem (Multidimensional Sexuality Questionnaire), and sexual distress (Sexual Distress Scale-Revised), during their first few sessions (ie, first to third sessions [the assessment phase]). Sexual distress was the main outcome, as measured with the Sexual Distress Scale-Revised. Results indicated that 54% (n = 376) of patients reported elevated sexual distress based on the questionnaire threshold score. Path analyses indicated an indirect effect in which higher dispositional mindfulness was associated with higher levels of sexual self-esteem, which in turn was associated with lower sexual distress. Results also highlighted that specific facets of mindfulness were related to higher sexual self-esteem (ie, describing, and nonreacting) and lower sexual distress (ie, nonjudgment and acting with awareness). The integrative model explained 23% of the variance of sexual distress scores. Findings suggest that addressing specifically sexual self-esteem and mindfulness may represent relevant clinical avenues to reduce sexual distress among sex therapy patients. Strengths of this study include the novel examination of the role of sexual self-esteem in the link between mindfulness disposition and sexual distress in a large clinical sample of patients seeking sex therapy. Limitations includes reliance on patient self-report and a cross-sectional design that limit conclusion regarding causality. This study makes a valuable contribution to the existing body of research highlighting the pivotal roles of sexual self-esteem in the link between dispositional mindfulness and reduced sexual distress among adults undergoing sex therapy, allowing us to identify potential targets of intervention.

Multi-omic analysis revealed the immunological patterns and diagnostic value of exhausted T cell-derived PTTG1 in patients with psoriasis

BackgroundPsoriasis, characterized by chronic inflammation, is a persistent skin condition that is notoriously challenging to manage and prone to relapse. Despite significant advancements in its treatment, many adverse reactions still occur. Therefore, exploring the mechanisms behind the occurrence and development of psoriasis is extremely important. MethodsThe weighted correlation network analysis (WGCNA) algorithm was used to identify phenotype-related genes in patients with psoriasis. We recruited clinical samples of patients with psoriasis, and used single-cell RNA sequencing (scRNA-seq) to visualize divergent genes and metabolisms of varied cells for the psoriasis. Various machine-learning methods were used to identify core genes, and molecular docking was used to analyze the stability of leptomycin B targeting pituitary tumor transforming 1 (PTTG1). Immunofluorescence (IHC) analysis, multiplex immunofluorescence (mIF) analysis, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to validate the results. ResultsOur results identified 1391 genes associated with the phenotype in patients with psoriasis and highlighted the significant alterations in T-cell functionality observed in the disease by WGCNA. There were nine distinct cellular clusters in psoriasis analyzed with the aid of scRNA-seq data. Each subtype of cell exhibited distinct genetic profiles, functional roles, signaling mechanisms, and metabolic characteristics. Machine-learning methods further demonstrated the potential diagnostic value of T cell-derived PTTG1 and its relationship with T-cell exhaustion in psoriasis. Lastly, the leptomycin B was scrutinized and verified had high stability targeting PTTG1. ConclusionsThis study elucidates the biological basis of psoriasis. At the same time, it was discovered that PTTG1 derived from exhausted T cells serves as a diagnostic biomarker for psoriasis. Leptomycin B could be a potential drug for targeted treatment of psoriasis on PTTG1.

A network analysis of eating disorder, PTSD, major depression, state-trait anxiety, and quality of life measures in eating disorder patients treated in residential care.

The network approach in the eating disorder (ED) field has confirmed important links between EDs and posttraumatic stress disorder (PTSD) symptoms. However, studies including comorbid symptoms are scarce, which limits our understanding of potentially important connections. We hypothesised that anxiety, depression and poor quality of life (QOL) would provide a more complete picture of central, maintaining factors. Network analysis using R was performed in 2178 adult ED patients (91% female) admitted to residential treatment. Assessments included the ED Examination Questionnaire (EDEQ), the Eating Disorders Inventory (EDI-2), the PTSD Checklist for DSM-5 (PTSD clusters (PCL-5)), the Patient Health Questionnaire (PHQ-9), the Spielberger State-Trait Anxiety Scale (STAI), and the ED QOL Scale (EDQOL), which measure symptoms of EDs, PTSD, major depression, state-trait anxiety, and QOL, respectively. EDI-2 ineffectiveness showed the highest centrality (expected influence) followed by EDI-2 interoceptive awareness, STAI state anxiety, EDEQ shape concern, EDQOL psychological subscale, and PTSD cluster D (hyperarousal) symptoms. Eating Disorder Quality of Life psychological and physical-cognitive subscales and PHQ-9 major depressive, STAI state anxiety and PCL-5 PTSD cluster E (negative alterations in mood and cognition) symptoms showed the highest bridge expected influence, suggesting their interactive role in maintaining ED-PTSD comorbidity. This is the first network analysis of the interaction between ED and PTSD symptoms to include the comorbid measures of depression, anxiety, and QOL in a large clinical sample of ED patients. Our results indicate that several symptom clusters are likely to maintain ED-PTSD comorbidity and may be important targets of integrated treatment.

Sex talks-experiences with and barriers to communication about sexuality with healthcare staff among patients with anxiety disorder in Denmark.

Previous research among diverse patient populations suggests that healthcare staff routinely do not talk about sexuality with their patients even when such talks are highly indicated and relevant. In this study we sought to investigate how patients at outpatient anxiety clinics in Denmark experience sexual communication with healthcare staff and what barriers they encounter in this connection. We employed a survey design from January 1, 2018, to June 30, 2019. In collaboration with 11 outpatient anxiety clinics in Denmark, patients with a primary diagnosis of panic disorder, social phobia, generalized anxiety, or obsessive-compulsive disorder were invited to participate in the study. The final sample included 272 patients. Survey questions were related to sociodemographic characteristics, sexual activity and dysfunctions, pharmacological treatment adherence, anxiety and depression symptoms, and experience with and barriers to sexual communication. For each participant, clinicians at the clinics provided the International Classification of Diseases, 10th revision, diagnostic codes, medications, and dosage. Study inclusion criteria were not having an organic disorder that may cause anxiety, not having a previous diagnosis of bipolar affective disorder or schizophrenia, and the ability to speak and read Danish. Outcomes included patients' experiences with and barriers to sexual communication with healthcare staff. In total, 61% of the patients in this sample group found it relevant to talk to healthcare staff about sexuality but only 28% of the study patients had done so, of whom 83% reported this communication to be a positive experience. The most frequently reported patient barriers to communication with healthcare professionals regarding sexual concerns were a belief that if sexual matters were relevant, the healthcare staff would bring it up (94%), fear of transgressing their own boundaries (94%), embarrassment (92%), and lack of knowledge as to how to start a conversation about sex (91%). The study results indicated a need for healthcare staff to routinely map out and address sexual matters in their clinical work with anxiety patients while bearing in mind the common patient barriers for this topic. This study included a large clinical outpatient sample of anxiety patients and an extensive survey. However, the results may not be generalizable across all anxiety patients or patients in general. The results of this study strongly indicate that a majority of anxiety patients find it both relevant and beneficial to discuss sexual matters with healthcare staff in connection with their anxiety treatment, and therefore healthcare staff should be educated and equipped to routinely address these matters while bearing in mind the most common patient barriers for conversations about sexuality.

Adaptation of the Cognitive Screening Test (Triagem Cognitiva – TRIACOG) for computer-mediated assessments: TRIACOG-Online

This study aims to present the adaptation, evidence of content validity and results of a pilot study of the Cognitive Screening Test - Online (TRIACOG-Online) in a clinical sample of patients after stroke. The process comprised four stages: 1) Adaptation of the instructions, stimulus and responses; 2) Seven experts analyzed the equivalence between the previous printed version and the online version; 3) A pilot study was carried out with seven adults who had experienced a stroke in order to check the comprehension and feasibility of the items; and 4) The development of the final version of TRIACOG-Online. Expert validity testing of the questionnaire yielded a content validity index (CVI) of 100% for correspondence and construct in 13 items, and a CVI of 87.71% in four items. In the pilot study, problems related to the internet led to the decision to use a single section form. No difficulties were observed in carrying out the tasks and understanding the instructions. Participants reported being able to adequately visualize the stimuli and remain motivated to complete the tasks presented. It was shown that TRIACOG-Online evaluated the same constructs as the pencil-and-paper version, can be used in remote neuropsychological assessments and face-to-face settings.

Validity of the Addiction-like Eating Behavior Scale among Patients with Compulsive Eating.

Food addiction (FA) and binge eating disorder (BED) co-occur and share compulsive eating symptoms. When using an FA measure, it is important to evaluate its performance in a population presenting compulsive eating. The study aims to validate the Addiction-like Eating Behavior Scale (AEBS) among a clinical sample characterized by compulsive eating and overweight/obesity and to evaluate its incremental validity over the Yale Food Addiction Scale 2.0 (YFAS). Patients seeking help for compulsive eating (n = 220), between January 2020 and July 2023, completed online questionnaires, including FA, compulsive eating, and BMI evaluations. The factor structure, internal consistency, and convergent, divergent, and incremental validity were tested. The sample had a mean age of 44.4 years old (SD = 12.7) and a mean BMI of 38.2 (SD = 8.0). The two-factor structure provided a good fit for the data, with factor loadings from 0.55 to 0.82 (except for item 15) and the internal consistency was high (ω = 0.84-0.89). The AEBS was positively correlated with the YFAS (r = 0.66), binge eating (r = 0.67), grazing (r = 0.47), craving (r = 0.74), and BMI (r = 0.26), and negatively correlated with dietary restraint (r = -0.37), supporting good convergent and divergent validity. For each measure of compulsive eating, linear regression showed that the AEBS "appetite drive" subscale had a unique contribution over the YFAS. This study provided evidence that the AEBS is a valid measure among a clinical sample of patients with compulsive eating and overweight/obesity. However, questions remain as to whether the AEBS is a measure of FA or compulsive eating.

Autistic traits as predictors of post-traumatic stress symptoms among patients with borderline personality disorder.

Autistic traits (AT) seem to be particularly frequent among patients with borderline personality disorder (BPD). Moreover, the autism spectrum is considered a vulnerability factor for the development of post-traumatic stress disorder (PTSD) symptoms, increasing the vulnerability of BPD subjects toward the development of a stress-related disorder. The study aimed to investigate the association between AT and trauma-related symptoms in a clinical sample of patients with BPD. A total of 48 patients with a clinical diagnosis of BPD and 52 healthy control (HC) subjects were recruited and assessed with the Adult Autism Subthreshold Spectrum Self-Report (AdAS Spectrum) questionnaire and the Trauma and Loss Spectrum-Self-Report questionnaire (TALS-SR). The BPD group was divided into two subgroups: BPD with a symptomatological diagnosis of PTSD (pBPD = 25) and BPD not diagnosed with PTSD (No-pBPD = 23). The clinical sample scored significantly higher in almost all AdAS domains. Moreover, pBPD groups reported higher AdAS and TALS-SR scores in the total and in various domains than the No-pBPD group, which scored higher in several domains than HC. AdAS Restricted interests and rumination domain scores were positive predictors of BPD presence independently from PTSD, while Inflexibility and adherence to routine domain was a negative predictor. Finally, AdAS Hyper/hyporeactivity to sensory stimuli domain was a positive predictor only for inclusion in the pBPD group. Our study confirmed the existence of a statistically significant relationship between the autism spectrum and BPD, while BPD subjects diagnosed with PTSD seem to show a higher autism spectrum burden.

An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting.

Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department. We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centra. We analyzed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or else. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine. The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI 92.3-98.3), while the accuracy for classification of MSU with using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI 87.9-95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI 82.7-92.2). The model was able to discriminate between pathologic crystals, artifacts, and other particles such as microplastics. We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.

Performance of an Autonomous Sanitary Sterilisation Ultraviolet Machine (ASSUM) on terminal disinfection of surgical theaters and rooms of an intensive-intermediate care unit

Ultraviolet- C (UV-C) light is effective for reducing environmental bioburden in hospitals, and the use of robots to deliver it may be advantageous. To evaluate the feasibility and clinical efficacy of an autonomous programmable UV-C robot in surgical and intensive care unit (ICU) rooms of a tertiary hospital. During ten consecutive months, the device was used in six theatres where cardiac, colorectal and orthopaedic surgeries were performed, and in the rooms previously occupied by patients subjected to contact precautions of a 14-bed ICU. Surgical site infection (SSI) rates of procedures performed in the UV-cleaned theatres were compared with those of the previous year. Incidence in clinical samples of ICU-acquired multiple-drug resistant (MDR) microorganisms was compared with that of the same period of the previous year. An UV-C exposure study done by semi-quantitative dosimeters and a survey of the bioburden on surfaces were carried out. SSI rates in the pre- and post-intervention periods were 8.67% (80/922) and 7.5% (61/813), respectively (p=0.37). Incidence of target microorganisms in clinical samples remained unchanged (38.4 vs. 39.4 per 10,000 patient-days, p=0.94). All the dosimeters exposed to ≤1 meter received ≥500 mJ/cm2. The bacterial load on surfaces decreased after the intervention, particularly in ICU rooms (from 4.57±7.4 CFU to 0.27±0.8 CFU, p<0.0001). Deployment of an UV-C robot in surgical and ICU rooms is feasible, ensures adequate delivery of germicidal UV-C light and reduces the environmental bacterial burden. Rates of surgical site infections or acquisition of MDR in clinical samples of critically-ill patients remained unchanged.

High prevalence of hepatitis E and rat hepatitis E viruses in wastewater in Gothenburg, Sweden

Hepatitis E virus (HEV) and Rat Hepatitis E virus (RHEV), recognized for their zoonotic potential, pose significant public health concerns. Our previous research identified both viruses in effluent wastewater in Gothenburg, Sweden. However, there are lingering inquiries regarding the prevalence and genetic diversity of these viruses in influent wastewater, as well as the utility of wastewater surveillance in elucidating their community circulation dynamics. To address these knowledge gaps, we conducted weekly collection of wastewater samples at the Rya wastewater treatment plant in Gothenburg throughout 2023. The concentrations of HEV and RHEV were quantified using quantitative polymerase chain reaction (qPCR). Additionally, two semi/nested-PCR were utilized to amplify viral strains. Furthermore, HEV strains from patients within the same region, as well as other regions in Sweden in 2023, were incorporated into the analysis. Remarkably, we observed a high prevalence of HEV (86%) and RHEV (98%) in wastewater samples, with the majority of HEV sequences identified as subtype 3c/i (9/12). In contrast, HEV subtype 3f was the most sequenced among clinical patient samples (6/12). Notably, previously unreported HEV-3b and unclassified strains were detected in wastewater. Almost all RHEV strains (20/21) were clustered into European groups, with none of the RHEV genetically close to strains previously found in human cases. The notable discordance in prevalence and identified subtypes of HEV-3 in wastewater compared to clinical samples suggests either a significant underdiagnosis of HEV infections or differences in viral loads and shedding durations among humans between HEV-3 subtypes. This underscores the urgent need for improved diagnostic techniques and heightened awareness of HEV transmission dynamics. Furthermore, the consistent detection of RHEV in wastewater underscores the necessity for further investigations to assess the potential role of RHEV in hepatitis cases of unknown etiology, given that most currently available clinical diagnostic assays fail to detect RHEV.

Antimicrobial Susceptibility of Methicillin-resistant Staphylococcus Aureus and Methicillin-sensitive Staphylococcus Aureus in a Pediatric Tertiary Care Hospital in Southern India

Objectives: To determine the current antimicrobial sensitivity profile of MRSA and compare it with the antimicrobial sensitivity of MSSA (Methicillin Sensitive Staphylococcus aureus) Material and Methods: Antimicrobial resistance in Staphylococcus aureus is a global public health concern. Methicillin-resistant Staphylococcus aureus (MRSA) is often resistant to the many classes of antibiotics compared to the methicillin-sensitive Staphylococcus aureus (MSSA). Five hundred and fifty S. aureus isolates obtained from clinical samples of pediatric patients were studied to determine the difference in the antimicrobial susceptibility between MRSA and MSSA. Results: Out of 550 S. aureus isolates, 59.3% were MSSA, and 40.7% were MRSA. The antimicrobial sensitivity to ciprofloxacin, gentamicin, clindamycin, erythomycin, tetracycline of MSSA was 26.4% , 93.6%, 81.5%, 61.2%, 95.4% respectively, and that of MRSA was 4.9%, 56.2%, 58%, 31%, 89.8% respectively. Conclusion: Antimicrobial sensitivity to ciprofloxacin, gentamicin, clindamycin, erythromycin, and tetracycline were significantly higher in MSSA than in MRSA.

Discrepancy Between Desired Time in Bed and Desired Total Sleep Time, Insomnia, Depression, and Dysfunctional Beliefs About Sleep Among a Clinical Sample of Patients With Insomnia.

This study investigated whether the discrepancy between desired time in bed and desired total sleep time (DBST) index could be a meaningful indicator for assessing insomnia severity in a clinical sample of patients with insomnia. Furthermore, we sought to identify the mediators of the association between DBST and insomnia severity in individuals with insomnia. We collected the medical records of 127 patients with insomnia. Each participant's DBST index was calculated using sleep indices, including time and duration variables. Psychological symptoms were investigated using the Insomnia Severity Index (ISI), Patients Health Questionnaire-9 items (PHQ-9), Generalized Anxiety Disorder-7, Dysfunctional Beliefs and Attitudes about Sleep-16 items (DBAS-16), and Epworth Sleepiness Scale. The DBST index was significantly correlated with the ISI (r=0.20, p<0.05), desired total sleep time (r=-0.52, p<0.001), and desired time in bed (r=0.32, p<0.01). Linear regression analysis revealed that insomnia severity was associated with age (β=-0.18, p=0.018), DBST (β=0.23, p=0.003), PHQ-9 (β=0.23, p=0.031), and DBAS-16 (β=0.42, p<0.001). The DBST directly influenced insomnia severity, although indirect effects of mediators were not significant. The DBST index directly influenced insomnia severity regardless of the mediating effects of psychological factors among a clinical sample of patients with insomnia. This finding implies that the DBST index can be a simple measure of insomnia severity, even among patients with insomnia.

Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.

Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants. To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program. A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment. The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy. ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.

Frequency of Mutacin Gene Types in Streptococcus mutans Isolated From Oral Potentially Malignant Disorder (OPMD) Patients.

Objectives Mutacins are potent virulent factors attributing to the virulence in Streptococcus mutans leading to oro-dental diseases, and oral potentially malignant disorders (OPMDs) are considered a premalignant condition of the oro-mucosal layers in the oral cavity. The purpose of this study was to phenotypically characterize S. mutans from the clinical samples of patients with OPMD and to assess the frequency of mutacin genes in comparison with healthy individuals. Methods Saliva samples (n=60) were collected from three different groups and the samples were incubated at 37°C for 48 hours in Mutans-Sanguis agar. After incubation, the isolates were identified phenotypically for S. mutans and the frequency of mutacin genes and its types were assessed by polymerase chain reaction (PCR). Results S. mutans was found to be more prevalent in the OPMD cases (45%) followed by healthy individuals with caries (15%). Mutacin genes were expressed in all the groups except Group 3 (healthy individuals) without caries. Mutacin I was expressed the highest in Group 1 and Group 2 with 88% and 62.5, respectively, and mutacin III was expressed the least in all groups with 0% expression. Conclusion The findings of the study show the presence of mutacin gene types in the clinical strains of S. mutans in association with OPMD and caries. Further experimental evidence may be required to assess the frequency and to design a novel drug targeting the same.