Multiplex detection and identification of viral, bacterial, and protozoan pathogens in human blood and plasma using an expanded high-density resequencing microarray platform.

Introduction: Nucleic acid tests for blood donor screening have improved the safety of the blood supply; however, increasing numbers of emerging pathogen tests are burdensome. Multiplex testing platforms are a potential solution. Methods: The Blood Borne Pathogen Resequencing Microarray Expanded (BBP-RMAv.2) can perform multiplex detection and identification of 80 viruses, bacteria and parasites. This study evaluated pathogen detection in human blood or plasma. Samples spiked with selected pathogens, each with one of 6 viruses, 2 bacteria and 5 protozoans were tested on this platform. The nucleic acids were extracted, amplified using multiplexed sets of primers, and hybridized to a microarray. The reported sequences were aligned to a database to identify the pathogen. To directly compare the microarray to an emerging molecular approach, the amplified nucleic acids were also submitted to nanopore next generation sequencing (NGS). Results: The BBP-RMAv.2 detected viral pathogens at a concentration as low as 100 copies/ml and a range of concentrations from 1,000 to 100,000 copies/ml for all the spiked pathogens. Coded specimens were identified correctly demonstrating the effectiveness of the platform. The nanopore sequencing correctly identified most samples and the results of the two platforms were compared. Discussion: These results indicated that the BBP-RMAv.2 could be employed for multiplex detection with potential for use in blood safety or disease diagnosis. The NGS was nearly as effective at identifying pathogens in blood and performed better than BBP-RMAv.2 at identifying pathogen-negative samples.

Early fetal sex determination using a fluorescent DNA nanosensing platform capable of simultaneous detection of SRY and DYS14 sequences in cell-free fetal DNA.

Early fetal sex determination is of crucial importance in the management of prenatal diagnosis of X-linked genetic abnormalities and congenital adrenal hyperplasia. The development of an efficient and simple method for high-sensitivity, affordable, and rapid screening of cell-free fetal DNA (cffDNA) is crucial for fetal sex determination in early pregnancy. In this study, single- and dual-fluorophore DNA biosensors based on multi-walled carbon nanotubes (MWCNT) were fabricated for the individual and simultaneous detection of the SRY gene and DYS14 marker in cffDNA obtained from maternal plasma samples. This nanosensing platform is based on the immobilization of single-stranded DNA (ssDNA) probes, labeled with ROX or FAM fluorophores, on MWCNT, resulting in the quenching of fluorescence emission in the absence of the targets. Upon the addition of the complementary target DNA (ctDNA) to the hybridization reaction, the fluorescence emission of fluorophore-labeled probes was significantly recovered to 79.5 % for ROX-labeled probes (i.e. SRY-specific probes), 81.5 % for FAM-labeled probes (i.e. DYS14-specific probes), and 65.9 % for dual-fluorophore biosensor compared to the quenching mode. The limit of detection (LOD) for ROX, and FAM was determined to be 4.5 nM, and 7.6 nM, respectively. For dual-color probes, LOD was found to be 5.4 (ROX) and 9.2 nM (FAM). Finally, the clinical applicability of the proposed method was confirmed through the detection of both biomarkers in maternal plasma samples, suggesting that the proposed nanosensing platform may be useful for the early detection of fetal sex using cffDNA.

Hepatitis B Risk Factors are Frequently Present in Children at Jinnah Postgraduate Medical Centre in Karachi.

Background: Infection with the hepatitis B virus (HBV) poses a serious threat to global public health. More than 300 million instances of chronic hepatitis are brought on by it, which is the primary cause of liver disease. This study was conducted to determine the risk factors of HBV in children at Jinnah Postgraduate Medical Centre, Karachi, Sindh, Pakistan. Materials and methods: This cross-sectional study was conducted at the Department of Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi, Sindh, Pakistan from January 2019 to April 2022. A total of 134 children aged below 16 years with HBV were recruited in this study. Demographic information was recorded. Screening for HBV was done in all patients. Investigations including liver biochemistry, hepatitis B surface antigen (HBsAg), and HBV DNA polymerase chain reaction (PCR) were conducted in the hospital along with a complete blood count and ultrasound whole abdomen. All information was collected on a predesigned proforma and evaluated using statistical package for the social sciences (SPSS), version 25.0, software. Results: The mean age of patients was 11.02 ± 2.19 years. There were 57.46% males. The frequent risk factor was vertical transmission in 47% of children followed by blood transfusion in 23.9% of children, horizontal transmission in 13.4% of children, and prior history of surgical or dental intervention in 17.2% of children. Conclusion: In this study, vertical transmission was the most common route of transmission of HBV. Additionally, 11% of family members were HBV positive. None had concomitant hepatitis C virus (HCV) and HDV infection. All pregnant females should be screened. Children on chronic blood transfusion therapy should be screened annually. Additionally, birth-dose HBV vaccination should be implemented as a key step in HBV prevention among Pakistani children. How to cite this article: Butt N, Kamani L, Khemani H. Hepatitis B Risk Factors are Frequently Present in Children at Jinnah Postgraduate Medical Centre in Karachi. Euroasian J Hepato-Gastroenterol 2024;14(1):16-19.

New tatt? We're ok with that! Relaxing the tattoo deferral for plasmapheresis donors maintains safety and increases donations.

BACKGROUND AND OBJECTIVES: Tattooing is one of the leading donor deferral reasons in Australia. Until September 2020, donors were deferred from all donation types for 4 months after a tattoo. At this time, our guideline changed such that donations of plasma for further manufacture were accepted immediately, provided the tattoo was administered in a licensed or regulated Australian establishment. We examined the effects of this change. MATERIALS AND METHODS: Donors with a tattoo deferral in the 2 years before or after the guideline change were identified and followed up until 3 November 2022. Between the two periods, we compared blood-borne virus (BBV) incidence, donor return, and the number of donors and donations regained after deferral. RESULTS: The incidence of BBV infection in donors after a tattoo deferral was zero in both periods. To exceed a residual risk of 1 in 1 million for hepatitis C virus, 190 donors would need to be infected yearly from a tattoo. Donors returned to donate significantly faster after the change (median return 85 days compared with 278 days). An extra 187 donations per 10,000 person-years of observation were gained, yielding a total of 44,674 additional plasma donations nationally 0-4 months after getting a tattoo. CONCLUSION: Allowing plasma donations immediately post-tattoo resulted in a substantial donation gain with no adverse safety effect. Lifeblood subsequently reduced the deferral for transfusible component donations to 7 days for tattoos in Australian licensed/regulated establishments.

Blood-borne viruses and neurological manifestations: An overview.

Infections caused by blood-borne viruses, such as human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV), are systemic diseases that can lead to a wide range of pathological manifestations. Besides causing severe immune and hepatic disorders, these viral pathogens can also induce neurological dysfunctions via both direct and indirect mechanisms. Neurological dysfunctions are one of the most common manifestations caused by these viruses that can also serve as indicators of their infection, impacting the clinical presentation of the disease. The main neurological manifestations of these blood-borne viral pathogens consist of several central and peripheral nervous system (CNS and PNS, respectively) dysfunctions. The most common neurological manifestations of HIV, HTLV, HCV, and HBV include HIV-associated peripheral neuropathy (PN), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HCV-/HBV-associated PN, respectively. Nonetheless, patients infected with these viruses may experience other neurological disorders, either associated with these conditions or manifesting in isolation, which can often go unnoticed or undiagnosed by physicians. The present review aims to provide an overview of the latest evidence on the relationship between blood-borne viruses and neurological disorders to highlight neurological conditions that may be somewhat overlooked by mainstream literature and physicians.

Serum albumin exposure enhances cell invasiveness and paclitaxel resistance in human neuroblastoma cells, with attenuation by valeriana-type iridoid glycosides.

Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood-borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFß and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre-exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana-type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood-borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana-type iridoid glycosides in anti-cancer treatment.

Unrevealing the therapeutic potential of artesunate against emerging zoonotic Babesia microti infection in the murine model.

Babesiosis, a zoonotic blood protozoal disease, threatens humans and animals and is difficult to treat due to growing antimicrobial resistance. The study aimed to investigate the therapeutic efficacy of artesunate (AS), a well-known derivative of artemisinin, against Babesia microti (B. microti) using a murine infection model. Male BALB/c mice (6 weeks old; 15 per group) were chosen and randomly divided into 1) the control group, 2) the B. microti group, and 3) the B. microti + artesunate treatment groups. AS treatment at 2 mg/kg, 4 mg/kg, and 8 mg/kg of body weight significantly (p < 0.05) reduced the B. microti load in blood smears in a dose-dependent manner. Additionally, AS treatment mitigated the decrease in body weight and restored the normal state of the liver and spleen viscera index compared to the B. microti-infected group after 28 days. Hematological analysis revealed significant increases in RBC, WBC, and PLT counts post-AS treatment compared to the B. microti-infected group. Furthermore, AS administration resulted in significant reductions in total protein, bilirubin, ALT, AST, and ALP levels, along with reduced liver and spleen inflammation and lesions as observed through histopathological analysis. AS also elicited dose-dependent changes in mRNA and protein expression levels of apoptotic, proinflammatory, and anti-inflammatory cytokines in the liver compared to the control and B. microti-infected groups. Immunolabeling revealed decreased expression of apoptotic and inflammation-related proteins in AS-treated hepatic cytoplasm compared to the B. microti-infected group. AS also in dose-dependent manner decreased apoptotic protein and increased Bcl-2. Overall, these findings underscore the potential of AS as an anti-parasitic candidate in combating B. microti pathogenesis in an in vivo infection model, suggesting its promise for clinical trials as a treatment for babesiosis.

Perspectives on digital testing services for sexually transmitted and blood-borne infections from Two-Spirit, gay, bisexual, transgender, and other queer Black, Indigenous, people of colour living in Ontario, Canada.

OBJECTIVES: Increased sexually transmitted and blood-borne infections (STBBI) testing can reduce the burden of disease among Two-Spirit, gay, bisexual, transgender, and other queer Black, Indigenous, people of colour (2SGBTQ+ BIPOC). However, this population encounters barriers, such as discrimination, when accessing in-person STBBI testing services. Digital STBBI testing, such as self-testing/collection kits ordered online and digital requisitions, may address some of these barriers. Our aim was to understand acceptability of free digital STBBI testing among 2SGBTQ+ BIPOC living in Ontario, Canada. DESIGN: We approached this analysis using Implementation Science and Critical Race Theory. We conducted interviews and focus groups with 21 2SGBTQ + BIPOC individuals from 2020-2021. Participants were asked about their perceptions of the benefits and drawbacks of digital STBBI testing, populations that would benefit from using these services, and recommendations for how these services may be implemented in Ontario. Interviews and focus groups were transcribed verbatim and analyzed using reflexive thematic analysis. RESULTS: Six themes emerged. Digital STBBI testing services: (1) May reduce oppression experienced by 2SGBTQ + BIPOC when testing in-person; (2) Should address the unique needs that 2SGBTQ + BIPOC experience due to other intersecting identities they possess; (3) Should adapt their services to suit the varying cultural contexts and living circumstances of 2SGBTQ + BIPOC; (4) Should be accessible to 2SGBTQ + BIPOC who hold diverse or no documentation; (5) Should be offered in multiple languages; (6) May be inaccessible to those without Internet access or devices. CONCLUSION: Digital STBBI testing is one strategy that may reduce discrimination experienced by 2SGBTQ + BIPOC when getting tested in-person. However, digital STBBI testing services may not address all the needs of 2SGBTQ + BIPOC. Racism and other forms of oppression embedded into in-person and digital testing services will need to be addressed to meet the needs of this diverse population.

Development of a multiplex polymerase chain reaction assay for detection of hepatitis C virus, hepatitis B virus, and human immunodeficiency virus 1.

BACKGROUND: Hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus 1 (HIV-1) are the most epidemic blood-borne viruses, posing threats to human health and causing economic losses to nations for combating the infection transmission. The diagnostic methodologies that depend on the detection of viral nucleic acids are much more expensive, but they are more accurate than serological testing. AIM: To develop a rapid, cost-effective, and accurate diagnostic multiplex polymerase chain reaction (PCR) assay for simultaneous detection of HCV, HBV, and HIV-1. METHODS: The design of the proposed PCR assay targets the amplification of a short conserved region featured with a distinguishable melting profile and electrophoretic molecular weight inside each viral genome. Therefore, this diagnostic method will be appropriate for application in both conventional (combined with electrophoresis) and real-time PCR facilities. Confirmatory in silico investigations were conducted to prove the capability of the approached PCR assay to detect variants of each virus. Then, Egyptian isolates of each virus were subjected to the wet lab examination using the given diagnostic assay. RESULTS: The in silico investigations confirmed that the PCR primers can match many viral variants in a multiplex PCR assay. The wet lab experiment proved the efficiency of the assay in distinguishing each viral type through high-resolution melting analysis. Compared to related published assays, the proposed assay in the current study is more sensitive and competitive with many expensive PCR assays. CONCLUSION: This study provides a simple, cost-effective, and sensitive diagnostic PCR assay facilitating the detection of the most epidemic blood-borne viruses; this makes the proposed assay promising to be substitutive for the mistakable and cheap serological-based assays.

How Sharp Objects Injuries Impact our Healthcare Workers: Unveiling Perspective and Preventive Imperatives.

Introduction Sharp object injuries in the medical field present a considerable occupational hazard for healthcare workers (HCWs), encompassing a spectrum of consequences from immediate discomfort to enduring health consequences. These injuries may expose HCWs to potential infections. Despite efforts to control sharp object injuries in healthcare environments, they are present at every stage involving using or disposing of medical sharp instruments. In Jordan, limited research has focused on sharp object injuries, with most data included from studies concentrating on practicing nurses or nursing students. Consequently, further research is necessary to comprehend the causes behind the high sharp object injury rate and the insufficient knowledge of safety practices and preventive guidelines. Objectives This study was conducted to investigate the impact of sharp object injuries on HCWs, underlying causes, and potential consequences causes of needlestick injuries. To highlight perspective and preventive imperatives. Methods and patients This retrospective institutional-based cross-sectional chart analysis was conducted by reviewing all sharp object injuries report sheets and extracting data directly from these reports for analysis. The study encompassed all reported cases occurring between 2018 and 2023. All the participants' data handling was accomplished according to the Declaration of Helsinki (2013) and the Health Insurance Portability and Accountability (HIPAA) Acts.  Results A total of 146 self-reported hospital workers were included in the study. Within the final cohort, 52.73% of the participants were male (77/146), with an average age at diagnosis of 38.6±7.87 years (ranging from 20 to 52 years). Conversely, females comprised 47.27% of the cohort population (69/146) and had an average age at diagnosis of 34.73±6.73 years (ranging from 19 to 47 years). The age group 20-29 years was the most prominent age group, statistical analysis of age and gender data revealed significant differences. The overall prevalence of sharp object injuries was 11.83%, indicating that a sizable portion of HCWs is at risk of exposure to bloodborne pathogens. Among the different professional categories, Physicians constituted the majority of sharp object injuries reported victims in 41 cases (28.08%), followed by nurses in 38 cases (26.02%). Statistical analysis of the profession's data revealed significant differences (P<0.001). Notably, sharp object injuries were most reported in wards. The leading procedures that caused sharp object injuries were identified as during needle recapping in 53 instances (36.30%), then followed by medical waste treatment in 32 cases (21.92%). The left hand was the most affected body part, reported in 83 cases (56.84%). All injured individuals reported the incident promptly. No seroconversions were documented within the reviewed cases during the study period. Conclusion Injuries caused by sharp objects persist as a significant danger for hospital employees, posing immediate harm and long-term health risks linked to bloodborne pathogens. The findings stress the continuous responsibility of healthcare institutions to prioritize staff safety by addressing the root causes of sharp object injuries and fostering reporting and prevention cultures. Underreporting reasons are diverse, encompassing factors like time constraints, fear of consequences, and the misconception of injury insignificance.

Experiences of the National Post-Exposure Prophylaxis Hotline (PEPline): Occupational PEP consultation needs and trends, 2014 to 2022.

BACKGROUND: The National Clinician Consultation Center operates the Post-Exposure Prophylaxis Hotline (PEPline), a federally-funded educational resource providing bloodborne pathogen exposure management teleconsultation to US clinicians. METHODS: Sixty-seven thousand one hundred nine occupational post-exposure prophylaxis (PEP) consultations (January 2014 to December 2022) were retrospectively analyzed to describe PEPline utilization and common inquiries addressed by National Clinician Consultation Center consultants. RESULTS: Most calls involved percutaneous incidents (70%); blood was the most common body fluid discussed (60%). Inpatient units were the most common exposure setting (35%) and licensed nursing professionals were the most common category of exposed workers (28%). Of 2,295 calls where workers had already initiated PEP for human immunodeficiency virus (HIV) prevention and time to first dose was known, 9% had initiated HIV PEP within 2 hours of exposure; almost 80% had initiated HIV PEP between 2 and 24 hours; 3% after 24 to 36 hours; 5% after 36 to 72 hours; and 2% after 72 hours. Calls from urgent care providers increased by 10% over time. Overall, more than 90% of callers requested support on risk assessment, including source person testing; other common questions involved PEP side effects and follow-up care. CONCLUSIONS: PEPline consultations can help raise awareness about PEP availability and timely initiation, and reduce stigma by addressing common misperceptions about bloodborne pathogen transmission mechanisms and likelihood, particularly regarding HIV.

Seroprevalence of SARS-CoV-2 and Hepatitis B Virus Coinfections among Ethiopians with Acute Leukemia.

SARS-CoV-2 and blood-borne viral coinfections are well reported. Nevertheless, little is known regarding the seroprevalence of SARS-CoV-2 and coinfection with blood-borne viruses in hematologic malignancy patients in Ethiopia. We aimed to assess the seroprevalence of SARS-CoV-2 and associated infections with hepatitis B and other viruses among adolescent and adult acute leukemia patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A cross-sectional study was conducted from July 2020 to June 2021. Blood samples were tested for the presence of anti-SARS-CoV-2, HBV, HCV, and HIV with ELISA kits and occult hepatitis B infection with a real-time polymerase chain reaction assay. Out of a total 110 cases, the SARS-CoV-2 seroprevalence was 35.5%. The prevalence showed a significant increment from July 2020 to the end of June 2021 (p = 0.015). In 22.7% and 2.7% of leukemia cases, HBV and HIV, respectively, were detected. No HCV was identified. The rate of SARS-CoV-2 coinfection with HBV and HIV was 28% (11/39) and 2.6% (1/39), respectively; however, there was no statistically significant association between SARS-CoV-2 seropositivity with HBV and HIV (p > 0.05). There is a need for viral screening in leukemia cases to monitor infections and inform management.

Knowledge, Attitudes, and Practices of Dental Students from Romania Regarding Self-Perceived Risk and Prevention of Infectious Diseases.

University education is a leading source of information for dental practitioners. Particular emphasis should be given to determining the extent to which students acquire positive knowledge, attitudes, and practices (KAP) and positive metacompetences beyond the scope of each studied dental discipline. We performed a cross-sectional questionnaire-based study among dentistry students from Romania to assess self-perceived risk of infectious diseases and their KAP on topics related to infectious disease prevention. The surveyed students presented good knowledge regarding personal protective equipment (PPE), and their PPE practices significantly correlated with the perceived usefulness of PPE. Only 45.1% correctly recognized all vaccine-preventable diseases (VPDs), but knowledge regarding VPDs significantly improved with increasing year of study (τb = 0.298, p = 0.001), confirming a positive education effect. Awareness regarding the need for screening for bloodborne viruses is poor; the majority of students had never performed a test for hepatitis C virus infection (HCV) (59.4%) or for human immunodeficiency virus (HIV) infection (60.4%). Furthermore, most respondents incorrectly considered themselves at high or very high risk of acquiring BBV, and perceived risk was inversely correlated with willingness to treat patients with hepatitis B virus (HBV) infection (τb = -0.214, p = 0.018), HCV infection (τb = -0.234, p = 0.013), or HIV infection (τb = -0.242, p = 0.006). This led to 3.0% of respondents stating that they would hypothetically deny dental treatment to a patient with HBV infection, 5.0% for HCV infection, and 10.9% for HIV infection, the proportion being significantly higher for HIV (z = -2.2, p = 0.026). In conclusion, better knowledge is needed among dental students regarding their own vaccination history, screening for bloodborne viruses, accurate estimates for their risk of acquiring bloodborne viruses during routine dental practice, and the existence of post-exposure measures following occupational exposure. Improving student knowledge and awareness could translate into a higher willingness to treat patients with chronic viral infections and into a safer and more inclusive dental practice. We propose an adaptation to the university curriculum to cover these key areas for targeted focus to empower future dental practitioners and to facilitate the improvement of across-discipline metacompetences for infection prevention and control.

Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Trøndelag Health Study in Norway.

PURPOSE: Bloodstream infections (BSI) and sepsis are important causes of hospitalization, loss of health, and death globally. Targetable risk factors need to be identified to improve prevention and treatment. In this study, we aimed to evaluate the association of chronic kidney disease (CKD) and risk of and mortality from BSI and sepsis in the general population during a 22-year period. METHODS: We conducted a prospective cohort study among participants in the population-based Norwegian HUNT Study, where 68,438 participated. The median follow-up time was 17.4 years. The exposures were estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in urine. The outcomes were hazard ratios (HR) of hospital admission or death due to BSI or sepsis. The associations were adjusted for age, sex, diabetes, obesity, systolic blood pressure, smoking status, and cardiovascular disease. RESULTS: Participants with eGFR < 30 ml/min/1.732 had HR 3.35 for BSI (95% confidence intervals (CI) 2.12-5.3) and HR 2.94 for sepsis (95% CI 1.82-4.8) compared to normal eGFR (≥ 90 ml/min/1.732). HRs of death from BSI and sepsis were 4.2 (95% CI 1.71-10.4) and 4.1 (95% CI 1.88-8.9), respectively. Participants with severely increased albuminuria (ACR > 30 mg/mmol) had HR 3.60 for BSI (95% CI 2.30-5.6) and 3.14 for sepsis (95% CI 1.94-5.1) compared to normal albumin excretion (ACR < 3 mg/mmol). HRs of death were 2.67 (95% CI 0.82-8.7) and 2.16 (95% CI 0.78-6.0), respectively. CONCLUSION: In this large population-based cohort study, CKD was clearly associated with an increased risk of BSI and sepsis and related death.

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review.

BACKGROUND: Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM: To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS: This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS: Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION: Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

Genotyping of ticks: first molecular report of Hyalomma asiaticum and molecular detection of tick-borne bacteria in ticks and blood from Khyber Pakhtunkhwa, Pakistan.

Multiple ticks (Acari: Ixodoidea) carrying Rickettsiales bacteria have significant importance for both human and animal health. Thus, the purpose of this work was to genetically analyze tick species and their associated Rickettsiales bacteria in animal hosts. In order to achieve these objectives, various animals (including camels, cattle, goats, sheep, dogs, and mice) were inspected in four districts (Mardan, Peshawar, Kohat, and Karak) of Khyber Pakhtunkhwa to collect ticks, while blood samples were collected from all the symptomatic and asymptomatic cattle in all four districts. A total of 234 ticks were obtained from 86 out of 143 (60.14%) host animals, which were morphologically identified as Rhipicephalus turanicus, Rhipicephalus microplus, Haemaphysalis cornupunctata, and Hyalomma asiaticum. Among these, their representative ticks (126/234, 53.85%) were processed for molecular confirmation using cytochrome c oxidase (cox1) gene. Obtained cox1 sequences of four different tick species showed 99.72%-100% maximum identity with their corresponding species reported from Pakistan, China, India, and Kazakhstan and clustered phylogenetically. This study presented the first genetic report of Hy. asiaticum ticks in Pakistan. Moreover, genetically confirmed tick species were molecularly analyzed by PCR for detection of Rickettsiales DNA using partial fragments of 16S rDNA, 190-kDa outer membrane protein A (ompA), and 120-kDa outer membrane protein B (ompB) genes. In addition, blood samples were analyzed to identify Rickettsiales bacteria using the aforementioned genes. Rickettsiales bacteria were found in 24/126 (19.05%) ticks and 4/16 (25.00%) in symptomatic cattle's blood. The obtained ompA and ompB sequences from Hy. asiaticum ticks showed 99.73%-99.87% with Candidatus Rickettsia shennongii and unidentified Rickettsia sp., whereas the obtained 16S rDNA sequences from cattle's blood and ticks (Hae. cornupunctata) showed 99.67% highest identity with Anaplasma phagocytophilum. The 16S rDNA sequence of Rickettsiales DNA from Rh. turanicus ticks showed 100% identity with Ehrlichia canis and unidentified Ehrlichia sp. Obtained sequences of Rickettsiales bacteria were grouped along with their respective species in phylogenetic trees, which were previously reported in Greece, Cuba, Iraq, Turkey, Pakistan, South Korea, and China (mainland and Taiwan). This extensive study explores the wide range of damaging ticks and their corresponding tick-borne bacteria in the area, suggesting a possible danger to both livestock and human communities.

Transcriptional landscape of long non-coding RNAs (lncRNAs) and its implication in viral diseases.

Long non-coding RNAs (lncRNAs) are RNA transcripts of size >200 bp that do not translate into proteins. Emerging data revealed that viral infection results in systemic changes in the host at transcriptional level. These include alterations in the lncRNA expression levels and triggering of antiviral immune response involving several effector molecules and diverse signalling pathways. Thus, lncRNAs have emerged as an essential mediatory element at distinct phases of the virus infection cycle. The complete eradication of the viral disease requires more precise and novel approach, thus manipulation of the lncRNAs could be one of them. This review shed light upon the existing knowledge of lncRNAs wherein the implication of differentially expressed lncRNAs in blood-borne, air-borne, and vector-borne viral diseases and its promising therapeutic applications under clinical settings has been discussed. It further enhances our understanding of the complex interplay at host-pathogen interface with respect to lncRNA expression and function.

Impact of harm minimization interventions on reducing blood-borne infection transmission and some injecting behaviors among people who inject drugs: an overview and evidence gap mapping.

BACKGROUND: This study aimed to synthetize the evidence on the effectiveness of harm minimization interventions on reducing blood-borne infection transmission and injecting behaviors among people who inject drugs (PWID) through a comprehensive overview of systematic reviews and evidence gap mapping. METHODS: A systematic review was conducted with searches in PubMed and Scopus to identify systematic reviews assessing the impact of interventions aimed at reducing the harms associated with injectable drug use. The overall characteristics of the studies were extracted and their methodological quality was assessed using AMSTAR-2. An evidence gap map was constructed, highlighting the most frequently reported outcomes by intervention (CRD42023387713). RESULTS: Thirty-three systematic reviews were included. Of these, 14 (42.2%) assessed the impact of needle/syringe exchange programs (NSEP) and 11 (33.3%) examined opioid agonist therapy (OAT). These interventions are likely to be associated with reductions of HIV/HCV incidence (10-40% risk reduction for NSEP; 50-60% for OAT) and sharing injecting paraphernalia (50% for NSEP, 25-85% for OAT), particularly when combined (moderate evidence). Behavioral/educational interventions were assessed in 12 reviews (36.4%) with most authors in favor/partially in favor of the use of these approaches (moderate evidence). Take-home naloxone programs and supervised-injection facilities were each assessed in two studies (6.1%), which reported inconclusive results (limited/inconsistent evidence). Most authors reported high levels of heterogeneity and risk of bias. Other interventions and outcomes were inadequately reported. Most systematic reviews presented low or critically low quality. CONCLUSION: The evidence is sufficient to support the effectiveness of OAT, NSEP and their combination in reducing blood-borne infection transmission and certain injecting behaviors among PWID. However, evidence of other harm minimizations interventions in different settings and for some outcomes remain insufficient.