New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.

Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system's power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract.

A deep learning-based model for detecting Leishmania amastigotes in microscopic slides: a new approach to telemedicine.

BACKGROUND: Leishmaniasis, an illness caused by protozoa, accounts for a substantial number of human fatalities globally, thereby emerging as one of the most fatal parasitic diseases. The conventional methods employed for detecting the Leishmania parasite through microscopy are not only time-consuming but also susceptible to errors. Therefore, the main objective of this study is to develop a model based on deep learning, a subfield of artificial intelligence, that could facilitate automated diagnosis of leishmaniasis. METHODS: In this research, we introduce LeishFuNet, a deep learning framework designed for detecting Leishmania parasites in microscopic images. To enhance the performance of our model through same-domain transfer learning, we initially train four distinct models: VGG19, ResNet50, MobileNetV2, and DenseNet 169 on a dataset related to another infectious disease, COVID-19. These trained models are then utilized as new pre-trained models and fine-tuned on a set of 292 self-collected high-resolution microscopic images, consisting of 138 positive cases and 154 negative cases. The final prediction is generated through the fusion of information analyzed by these pre-trained models. Grad-CAM, an explainable artificial intelligence technique, is implemented to demonstrate the model's interpretability. RESULTS: The final results of utilizing our model for detecting amastigotes in microscopic images are as follows: accuracy of 98.95 1.4%, specificity of 98 2.67%, sensitivity of 100%, precision of 97.91 2.77%, F1-score of 98.92 1.43%, and Area Under Receiver Operating Characteristic Curve of 99 1.33. CONCLUSION: The newly devised system is precise, swift, user-friendly, and economical, thus indicating the potential of deep learning as a substitute for the prevailing leishmanial diagnostic techniques.

Empagliflozin and colchicine in patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction: a randomized, double-blinded, three-arm parallel-group, controlled trial.

PURPOSE: There is accumulating evidence regarding the potential benefits of empagliflozin in individuals with acute myocardial infarction (MI). Based on the literature, colchicine could also reduce the risk of MI and death in individuals with cardiovascular disease (CVD). However, trials investigating the effects of the combination of empagliflozin with colchicine and high-dose empagliflozin monotherapy in this setting are lacking. METHODS: In this trial, 106 non-diabetic participants with reduced left ventricular ejection fraction (LVEF) following recent ST-elevation MI were randomly assigned to empagliflozin 10 mg/day, empagliflozin 10 mg/day plus colchicine 0.5 mg twice daily, or empagliflozin 25 mg/day groups within 72 h after primary percutaneous coronary intervention (PCI). The study's primary outcomes were the changes in New York Heart Association (NYHA) functional class and high-sensitivity C-reactive protein (hs-CRP) over 12 weeks. RESULTS: The baseline characteristics of individuals were statistically similar between the study groups. Changes in NYHA functional class over 12 weeks were not significantly different between the study groups. hs-CRP was significantly reduced in all groups (all P < 0.001); however, there was no significant change between the groups over the study period. Changes in tumor necrosis factor-alpha (TNF-α), LVEF, and left ventricular end-diastolic dimension (LVEDD) during the research period did not differ significantly between groups. CONCLUSION: This study showed that neither the combination treatment of empagliflozin 10 mg/day with colchicine nor the monotherapy of empagliflozin 25 mg/day was superior to empagliflozin 10 mg/day in terms of changes in clinical, inflammatory, and echocardiographic outcome parameters in patients with recent MI with reduced LVEF over 3 months. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical trial ID: IRCT20111206008307N39. Registration date: 27 October 2022. https://www.irct.ir/trial/66216.

Could admission level of uric acid predict total diuretic dose in acute heart failure?

BACKGROUND: Recent studies have shown that increases in serum UA levels are associated with adverse clinical outcomes in patients with chronic heart failure (CHF); the aim of this study was to determine the relationship between serum uric acid and total diuretic dose received during hospitalization in hospitalized patients with acute exacerbation of heart failure. The main purpose of this study is to determine the role of uric acid as a biomarker that can be a substitute for pro-BNP in clinical evaluation and the need for diuretics in hospitalized patients with acute heart failure. METHODS: After approving the plan in the Research Council of the Heart Department and obtaining an ethical code from the Regional Committee on Research Ethics (Human Subjects Studies), the researcher referred to the archives of our center, the case of 100 patients diagnosed with acute heart failure. Cardiac patients were selected, and the information required for the study was collected using a pre-prepared data collection form, and the information was entered into SPSS software after categorization and appropriate analysis and statistical tests were performed on it. Were performed and in all statistical tests the statistical significance level was considered 0.05: RESULTS: 100 patients with acute heart failure were included in this study with a mean age of 63.43 ± 14.78 years. 66% of them were men. The mean dose of furosemide in these patients was 680.92 ± 377.47 mg and the mean serum uric acid level in these patients was 8.55 ± 2.50 mg / dL. In the study of the relationship between the variables, there was a significant relationship between the dose of furosemide received with the serum level of serum uric acid (P = 0.017, r = 0.248 and P = 0.009, r = -0.267, respectively). There is also a significant relationship between serum uric acid level and patient mortality (P = 0.013, r = 0.247). However this relationship lost its significance after multivariate analysis. CONCLUSION: There is a significant relationship between serum uric acid level and diuretic use. However, in-hospital mortality is not related to uric acid levels at admission.

Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin. After treatment, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze PD-L1, CTLA-4, and VISTA gene expression in the SW-1116 cell line. The upregulation of VISTA expression showed a significant increase (p < 0.0001) in response to both chemotherapy agents. Moreover, the expression of CTLA-4 exhibited a remarkable level of significance (p < 0.0001), and PD-L1 expression also displayed notable significance (p < 0.0001). Chemotherapeutic agents heighten immune checkpoint gene expression, highlighting potential immune response pathway modulation.

Evaluation of the immune checkpoint factors in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B-cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone.

BACKGROUND: Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH). METHODS: In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4+ IL17+) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs. RESULTS: The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORÉ£t and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells. CONCLUSION: Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC.

Potent SARS-CoV2-specific T-cell response in asymptomatic hemodialysis patients with hidden COVID-19 infection history.

BACKGROUND: COVID-19-related immune responses in patients with end-stage renal disease (ESRD) are characterized in detail by the humoral response, but their cellular immunity has not been clarified. Here, we evaluated virus-specific T cells in parallel with serology-related tests. METHODS: In this study, 104 ESRD patients at the hemodialysis ward of Imam Reza hospital at Tabriz (Iran) were enrolled. After blood sampling, SARS-CoV2-specific humoral and cellular immune responses were evaluated by SARS-CoV2-specific IgM/IgG ELISA and peptide/MHCI-Tetramers flow cytometry, respectively. RESULTS: Our results showed that 14 (13.5%) and 45 (43.3%) patients had specific SARS-CoV2 IgM and IgG in their sera, respectively. Immunophenotyping for SARS-CoV2-specific CD8+ T lymphocytes revealed that 68 (65.4%) patients had these types of cells. Among SARS-CoV2-specific CD8+ T lymphocytes positive subjects, 13 and 43 individuals had positive results for specific SARS-CoV2 IgM and IgG existence, respectively. Also, there was a relationship between specific SARS-CoV2 IgM (p = 0.031) and IgG (p < 0.0001) existence and having SARS-CoV2-specific TCD8+ lymphocytes in the studied population. CONCLUSION: Despite not having clinical symptoms, a high rate of SARS-CoV2-specific T-cell response in asymptomatic ESRD patients may reveal a high burden of asymptomatic COVID-19 infection in these patients.

Miniature Integrated 2.4 GHz Rectennas Using Novel Tunnel Diodes.

This work presents the design, fabrication, and measured results of a fully integrated miniature rectenna using a novel tunnel diode known as the Asymmetrical Spacer Layer Tunnel (ASPAT). The term rectenna is an abbreviation for a rectifying antenna, a device with a rectifier and antenna coexisting as a single design. The ASPAT is the centrepiece of the rectifier used for its strong temperature independence, zero bias, and high dynamic range. The antenna is designed to be impedance matched with the rectifier, eliminating the need for a matching network and saving valuable real estate on the gallium arsenide (GaAs) substrate. The antenna is fully integrated with the rectifier on a single chip, thus enabling antenna miniaturisation due to the high dielectric constant of GaAs and spiral design. This miniaturisation enables the design to be fabricated economically on a GaAs substrate whilst being comparable in size to a 15-gauge needle, thus unlocking applications in medical implants. The design presented here has a total die size of 4 × 1.2 mm2, with a maximum measured output voltage of 0.97 V and a 20 dBm single-tone 2.35 GHz signal transmitted 5 cm away from the rectenna.

Therapeutic potential of mesenchymal stem cell-derived exosomes as a cell-free therapy approach for the treatment of skin, bone, and cartilage defects.

OBJECTIVE: The aim of this study was to collect the articles concerning mesenchymal stem cell (MSC)-derived exosomes for regeneration of bone, cartilage and skin defects. METHOD: Scopus, PubMed, EMBASE, and Web of Science were searched for keywords "Exosome, MSC, Skin, Bone and Cartilage defects, Regenerative medicine, and extracellular vesicles. RESULTS: MSC-derived exosomes can emulate the biological activity of MSCs by horizontal transfer of multiple functional molecules including mRNAs, miRNAs, proteins, and lipids to the local microenvironment and recipient cells, and subsequently mediate restoring homeostasis and tissue regeneration through various mechanisms. Compared to MSCs, MSC-derived exosomes reveal many advantages such as non-immunogenicity, easy access, easy preservation, and extreme stability under various conditions. CONCLUSION: Hence, exosomes could be considered as an alternative strategy for cell-based therapies in regenerative medicine. In this paper, after describing the characteristics of exosomes, we will review the recent literature on the therapeutic potentials of MSC-derived exosomes in skin, bone, and cartilage repair.

Symptom recognition and treatment-seeking behaviors in women experiencing acute coronary syndrome for the first time: a qualitative study.

BACKGROUND: Women are more likely to delay medical help-seeking for ACS symptoms. Understanding patients' experience of the symptoms and their response is essential in improving help-seeking behaviors and timely diagnosis and treatment for ACS. This study aimed to explore women's experience of ACS, their response to the symptoms, and treatment-seeking decisions. METHODS: This qualitative descriptive study was conducted in a tertiary referral specialized heart hospital affiliated with Tabriz University of Medical Sciences, Iran. Participants included 39 women who had experienced ACS for the first time. RESULTS: Four main themes emerged from the analysis of interview transcripts: (1) the onset of symptoms, (2) the types of symptoms, (3) response to symptoms and (4) arriving at the hospital. These themes and associated sub-themes explained women's experience of ACS symptoms, their response to the symptoms, and decision to seek medical help. CONCLUSIONS: This study identified and discussed factors contributing to the prehospital delay in women and their decision-making to seek medical care for ACS symptoms. The results are consistent with previous research indicating that ACS symptoms in women are somewhat different from men, and women tend to underestimate their symptoms and attribute them to non-cardiac causes. Women should be supported to develop awareness and understanding of ACS symptoms and appreciate the importance of early treatment-seeking in the disease outcomes.

Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status.

BACKGROUND AND AIMS: Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component of the antioxidant defense and plays a crucial role in cardiovascular health. This study aimed to investigate the effects of daily consumption of sodium selenite and Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of oxidative stress in patients with atherosclerosis. METHODS AND RESULTS: In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients with atherosclerosis were recruited. Participants received 200 µg/day of sodium selenite, Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes' mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline and following the intervention. Following sodium selenite and Se-enriched yeast supplementation, the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption caused a statistically significant decrease in the change of MDA level (p < 0.05). CONCLUSION: In summary, these findings showed that Se supplementation may reduce inflammation through down-regulation of some pro-inflammatory genes, improving antioxidant defenses in atherosclerosis patients. Further research is required to come to a definite conclusion of selenium supplementation on the CVD risk. This study was registered on the Iranian Registry of Clinical Trials website (identifier: RCT20110123005670N28; https://www.irct.ir/).

Lightweight Fine-Grained Access Control for Wireless Body Area Networks.

Wireless Body Area Network (WBAN) is a highly promising technology enabling health providers to remotely monitor vital parameters of patients via tiny wearable and implantable sensors. In a WBAN, medical data is collected by several tiny sensors and usually transmitted to a server-side (e.g., a cloud service provider) for long-term storage and online/offline processing. However, as the health data includes several sensitive information, providing confidentiality and fine-grained access control is necessary to preserve the privacy of patients. In this paper, we design an attribute-based encryption (ABE) scheme with lightweight encryption and decryption mechanisms. Our scheme enables tiny sensors to encrypt the collected data under an access control policy by performing very few computational operations. Also, the computational overhead on the users in the decryption phase is lightweight, and most of the operations are performed by the cloud server. In comparison with some excellent ABE schemes, our encryption mechanism is more than 100 times faster, and the communication overhead in our scheme decreases significantly. We provide the security definition for the new primitive and prove its security in the standard model and under the hardness assumption of the decisional bilinear Diffie-Hellman (DBDH) problem.

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with squamous cell carcinoma in situ and actinic keratosis - a single-center cohort study.

To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post-transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV), and Lyon IARC polyomavirus (LIPyV) were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant versus benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development.

Respiratory tract virus infections in the elderly with pneumonia.

BACKGROUND: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. RESULTS: Median age of the patients was 83 years (range 76-90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 109/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes. CONCLUSION: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons.

Newly detected DNA viruses in juvenile nasopharyngeal angiofibroma (JNA) and oral and oropharyngeal squamous cell carcinoma (OSCC/OPSCC).

PURPOSE: Approximately 20% of cancers are estimated to have a viral etiology. We aimed to investigate whether DNA of 8 human parvoviruses [bocavirus 1-4 (HBoV1-4), parvovirus B19 (B19V), protoparvoviruses (bufa-, tusa-, and cutavirus)] and 13 human polyomaviruses (HPyV) can be detected in oropharyngeal and oral cavity squamous cell carcinoma (OPSCC/OSCC), and in juvenile nasopharyngeal angiofibroma (JNA) tissue samples. METHODS: Fresh samples of seven JNA tissues and ten paired tissues of OSCC/OPSCC tumor and adjacent healthy tissues were collected. DNA extraction and real-time PCRs were performed to detect HBoV1-4, B19V, bufa- tusa- and cutavirus, and HPyV genomes. RESULTS: JNA specimens were negative for all parvoviruses tested, whereas one JNA sample was Merkel cell polyomavirus (MCPyV) DNA positive. The OSCC/OPSCC samples were negative for the human protoparvoviruses, HBoV1-4, and all human polyomaviruses, except for one patient that was MCPyV DNA positive in both healthy and tumor tissues. Seven OSCC/OPSCC patients were positive for B19V DNA, three of them in both healthy and cancerous tissues and three in only healthy tissues. Three of the B19V DNA-positive patients harbored viral genotype 1, three genotype 2, and one genotype 3B. CONCLUSIONS: These are the first reports of MCPyV and B19V DNA being detected in JNA and OPSCC. The significance of viral DNA positivity is unclear. B19V DNA is known to remain in the tissues lifelong, however, it is of interest that there are some patients with B19 DNA in healthy tissue, but not in the corresponding cancer tissue.

Global Distribution of Human Protoparvoviruses.

Development of next-generation sequencing and metagenomics has revolutionized detection of novel viruses. Among these viruses are 3 human protoparvoviruses: bufavirus, tusavirus, and cutavirus. These viruses have been detected in feces of children with diarrhea. In addition, cutavirus has been detected in skin biopsy specimens of cutaneous T-cell lymphoma patients in France and in 1 melanoma patient in Denmark. We studied seroprevalences of IgG against bufavirus, tusavirus, and cutavirus in various populations (n = 840), and found a striking geographic difference in prevalence of bufavirus IgG. Although prevalence was low in adult populations in Finland (1.9%) and the United States (3.6%), bufavirus IgG was highly prevalent in populations in Iraq (84.8%), Iran (56.1%), and Kenya (72.3%). Conversely, cutavirus IgG showed evenly low prevalences (0%-5.6%) in all cohorts, and tusavirus IgG was not detected. These results provide new insights on the global distribution and endemic areas of protoparvoviruses.

Factors Influencing Various Aspects of Patients' Knowledge of Oral Anticoagulation.

OBJECTIVES: To identify and examine individual characteristics and socioeconomic factors that contribute to the knowledge of patients who receive warfarin anticoagulation. METHODS: All patients treated using warfarin for anticoagulation were enrolled during a 6-month period at a university-affiliated cardiac clinic. All relevant demographic and clinical information were collected and the Anticoagulation Knowledge Assessment (AKA) questionnaire consisting of 29 questions was administered. After completion, the questionnaires were scored and the percent correct answers were analyzed for overall scores, as well as the following categories: drug/food interactions, pharmacological knowledge, recognition of complications, and patient compliance. Multiple linear regression analysis was used to identify the contributing factors to the knowledge level of the patients in each category. RESULTS: One hundred fifty patients (79 men and 71 women) with a median age of 61.5 years completed the AKA questionnaire. The average overall score was 29.3%. Living alone (P = 0.008), higher levels of education (P = 0.001), and durations of ≥3 years of warfarin therapy (P = 0.018) positively impacted overall AKA scores. CONCLUSIONS: Socioeconomic factors and level of general education remain the most important elements determining the patient awareness of therapeutic goals, possible drug/food interaction, recognition of adverse effects, and compliance of warfarin treatment.

Sera of Peruvians with fever of unknown origins include viral nucleic acids from non-vertebrate hosts.

Serum samples collected from 88 Peruvians with unexplained fever were analyzed for viral sequences using metagenomics. Nucleic acids of anelloviruses, pegivirus A (GBV-C), HIV, Dengue virus, and Oropouche virus were detected. We also characterized from two sera the RNA genomes of new species of partitivirus and dicistrovirus belonging to viral families known to infect fungi or arthropod, respectively. Genomic DNA of a putative fungal cellular host could be PCR amplified from the partitivirus-containing serum sample. The detection in human serum of nucleic acids from viral families not known to infect vertebrates may indicate contamination during sample collection and aliquoting or human infection by their presumed cellular host, here a fungus. The role, if any, of the non-vertebrate infecting viruses detected in serum in inducing fever is unknown.