Heat shock protein A4 ablation leads to skeletal muscle myopathy associated with dysregulated autophagy and induced apoptosis.

BACKGROUND: Molecular chaperones assist protein folding, facilitate degradation of misfolded polypeptides, and thereby maintain protein homeostasis. Impaired chaperone activity leads to defective protein quality control that is implicated in multiple skeletal muscle diseases. The heat shock protein A4 (HSPA4) acts as a co-chaperone for HSP70. Previously, we showed that Hspa4 deletion causes impaired protein homeostasis in the heart. However, its functional role in skeletal muscle has not been explored. METHODS: We performed a comparative phenotypic and biochemical analyses of Hspa4 knockout (KO) mice with wild-type (WT) littermates. RESULTS: HSPA4 is markedly upregulated in regenerating WT muscle in vivo, and in differentiated myoblasts in vitro. Hspa4-KO mice are marked by growth retardation and increased variability in body weight, accompanied by 35% mortality rates during the peri-weaning period. The surviving Hspa4-KO mice experienced progressive skeletal muscle myopathy, characterized by increased number of muscle fibers with centralized nuclei, heterogeneous myofiber size distribution, inflammatory cell infiltrates and upregulation of embryonic and perinatal myosin heavy chain transcripts. Hspa4-KO muscles demonstrated an accumulation of autophagosome-associated proteins including microtubule associated protein1 light chain 3-II (LC3-II) and p62/sequestosome accompanied by increased number of TUNEL-positive nuclei. CONCLUSIONS: Our findings underscore the indispensable role of HSPA4 in maintenance of muscle integrity through contribution in skeletal muscle autophagy and apoptosis, which might provide a novel therapeutic strategy for skeletal muscle morbidities.

The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients.

Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol. Herein, we aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) at the genes coding for 2 SOF metabolizing enzymes: histidine triad nucleotide-binding protein 1 (HINT1) rs4696/rs7728773 and nucleoside diphosphate kinase 1 (NME1) rs3760468, together with the most potent anti-HCV innate molecule, i.e., interferon lambda 3 (IFNL3) rs12979860 and the response to SOF/DCV in Egyptian patients chronically infected with genotype 4 (GT4). SNPs were genotyped using real-time PCR in DNA from patients who achieved sustained virological response (SVR) at 12 weeks post-SOF/DCV treatment (i.e., responders; n = 188), patients who failed to achieve SVR12 (i.e., non-responders; n = 109), and healthy controls (n = 62). Our results demonstrated that patients bearing HINT1 rs7728773 CT/TT (odds ratio 2.119, 95% CI 1.263-3.559, p = 0.005) and IFNL3 rs12979860 CC (odds ratio 3.995, 95% CI 2.126-7.740, p = 0.0001) were more likely to achieve SVR12. However, neither HINT1 rs4696 nor NME1 rs3760468 seems to contribute to the responsiveness to SOF/DCV. Binary regression analysis defined 5 predictor factors independently associated with SVR12: age, bilirubin, hemoglobin, early stages of fibrosis, and combined HINT1 rs7728773 and IFNL3 rs12979860 favorable and mixed genotypes (odds ratio 3.134, 95% CI 1.518-6.47, p = 0.002), and that was confirmed by the combined ROC curve for the 5 predictor factors (AUC = 0.91, 95% CI 0.869-0.95, P = 0.0001). In conclusion, these data suggest that the two SNPs have the potential in predicting the response rate to SOF/DCV treatment in patients infected with HCV GT4. This study is the first to investigate the pharmacogenetics of SOF metabolizing enzyme and introduce HINT1 rs7728773 as a novel SNP that predicts the treatment efficacy.

Hepatitis A Virus Genotype IB Outbreak among Internally Displaced Persons, Syria.

In 2018, a hepatitis A virus outbreak was identified among internally displaced persons in Syria. Sequence analysis based on the viral protein 1/2A junction revealed that the causative virus belonged to genotype IB. A high displacement rate, deteriorated sanitary and health conditions, and poor water quality likely contributed to this outbreak.

Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014.

BACKGROUND: Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). METHODS: For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity. RESULTS: The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play. CONCLUSIONS: These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

Global Role and Burden of Influenza in Pediatric Respiratory Hospitalizations, 1982-2012: A Systematic Analysis.

BACKGROUND: The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. METHODS AND FINDINGS: We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5-17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%-11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%-7%) among children <6 mo to 16% (95% CI 14%-20%) among children 5-17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y-of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo-and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings. CONCLUSIONS: Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.

Severe Acute Respiratory Illness Deaths in Sub-Saharan Africa and the Role of Influenza: A Case Series From 8 Countries.

BACKGROUND: Data on causes of death due to respiratory illness in Africa are limited. METHODS: From January to April 2013, 28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)-associated deaths identified from influenza surveillance during 2009-2012. RESULTS: Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%-25.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%-5.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus-negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0-4 years, 462 (43.1%) involved people aged 5-49 years, and 209 (19.5%) involved people aged ≥50 years. CONCLUSIONS: Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.

Respiratory distress and early neonatal lethality in Hspa4l/Hspa4 double-mutant mice.

Heat shock proteins HSPA4L and HSPA4 are closely related members of the HSP110 family and act as cochaperones. We generated Hspa4l(-/-)Hspa4(-/-) mice to investigate a functional complementarity between HSPA4L and HSPA4 during embryonic development. Hspa4l(-/-)Hspa4(-/-) embryos exhibited marked pulmonary hypoplasia and neonatal death. Compared with lungs of wild-type, Hspa4l(-/-), and Hspa4(-/-) embryos, Hspa4l(-/-)Hspa4(-/-) lungs were characterized by diminished saccular spaces and increased mesenchymal septa. Mesenchymal hypercellularity was determined to be due to an increased cell proliferation index and decreased cell death. A significant increase in expression levels of prosurvival protein B cell leukemia/lymphoma 2 may be the cause for inhibition of apoptotic process in lungs of Hspa4(-/-)Hspa4l(-/-) embryos. Accumulation of glycogen and diminished expression of surfactant protein B, prosurfactant protein C, and aquaporin 5 in saccular epithelium suggested impaired maturation of type II and type I pneumocytes in the Hspa4l(-/-)Hspa4(-/-) lungs. Further experiments showed a significant accumulation of ubiquitinated proteins in the lungs of Hspa4l(-/-)Hspa4(-/-) embryos, indicating an impaired chaperone activity. Our study demonstrates that HSPA4L and HSPA4 collaborate in embryonic lung maturation, which is necessary for adaptation to air breathing at birth.

A phased strengthening of laboratory capacity in the Eastern Mediterranean Region during the COVID-19 pandemic.

The Eastern Mediterranean Region (EMR) faces ongoing challenges in its public health system due to limited resources, logistical issues, and political disruptions. The COVID-19 pandemic accelerated the need for stronger laboratory capacities to handle the increased demand for testing. In a phased response, EMR countries utilized the National Influenza Centers to rapidly establish and scale molecular testing for SARS-CoV-2, the causative agent of COVID-19. The expansion of capacity included strong collaborations between public health bodies and private and academic sectors to decentralize and expand testing to the subnational level. To ensure that the quality of testing was not impacted by rapid expansion, national and subnational laboratories were enrolled in external quality assurance programs for the duration of the response. Implementation of genomic surveillance was prioritized for variant tracking, leading to the establishment of regional sequencing reference laboratories and the distribution of MinION sequencing platforms to complex emergency countries who previously had limited experience with pathogen sequencing. Challenges included a lack of technical expertise, including in implementing novel diagnostic assays and sequencing, a lack of bioinformatics expertise in the region, and significant logistical and procurement challenges. The collaborative approach, coordinated through the WHO Eastern Mediterranean Regional Office, enabled all 22 countries to achieve SARS-CoV-2 diagnostic capabilities, highlighting the pivotal role of laboratories in global health security.

Development of chia gum/alginate-polymer support for horseradish peroxidase immobilization and its application in phenolic removal.

Chia gum's molecular structure with distinctive properties as well as the alginate-based hydrogel's three-dimensionally cross-linked structure can provide a potent matrix for immobilization of enzyme. Herein, chia gum (CG)/alginate (A)-polymeric complex was synthesized and employed as a support material for the immobilization of horseradish peroxidase (HRP). HRP was successfully immobilized on the developed ACG-polymeric support, and the highest immobilization recovery (75%) was observed at 1.0% CG and 2% A, pH 7.0, and 50 units of the enzyme. The structure, morphology, and thermal properties of the prepared ACG-HRP were demonstrated using Fourier Transform Infrared (FTIR), Scanning Electron Microscope, and Thermogravimetric (TGA) analyses. ACG-HRP showed a good reusability (60%) over ten reuses. The immobilized ACG-HRP displayed an acidic pH optimum (6.0), a higher temperature optimum (50 °C), and improved thermal stability (30-50 °C) compared to the soluble HRP at pH 7.0, 40 °C and (30-40 °C), respectively. ACG-HRP has a lower affinity for hydrogen peroxide (H2O2) and guaiacol and a higher oxidizing affinity for a number of phenolic substrates. The ACG-HRP demonstrated greater resistance to heavy metals, isopropanol, urea, Triton X-100, and urea, as well as improved efficiency for eliminating phenol and p-chlorophenol. The developed ACG-polymeric support provided improved enzyme properties, allowed the reuse of the immobilized HRP in 10 cycles, and made it promising for several biotechnological applications.

Strengthening laboratories in response to outbreaks in humanitarian emergencies and conflict settings: Results, challenges and lessons from expanding PCR diagnostic capacities for COVID-19 testing in Yemen.

BACKGROUND: When the COVID-19 pandemic was declared, Yemen, a country facing years of conflict had only one laboratory with PCR testing capacity. In this article, we describe the outcome of the implementation of molecular based diagnostics platform in Yemen and highlight the key milestones the country went through to increase access to testing for its populations residing in a geographically vast and politically divided country. METHODS: A retrospective assessment of COVID-19 laboratory response activities was done detailing the needs assessment process, timelines, geographical coverage, and outcomes of the activities. Laboratory data was analyzed to construct the geographical locations of COVID-19 testing laboratories and the numbers of tests performed in each facility to highlight the demands of testing for travelers. Finally, we discuss the impact these activities had in enabling the movement of people across international borders for economic gains and in delivery of critical humanitarian aid. OUTCOME: PCR testing capacities in Yemen significantly improved, from one laboratory in Sanaa in April 2020 to 18 facilities across the country by June 2022. In addition, the number of functional Real-Time PCR thermocyclers increased from one to 32, the PCR tests output per day improved from 192 to 6144 tests per day. Results from analysis of laboratory data showed there were four peaks of COVID-19 in Yemen as October 2022. The majority of laboratory tests were performed for travelers than for medical or public health reasons. Demand for laboratory testing in Yemen was generally low and waned over time as the perceived risk of COVID-19 declined, in parallel with rollout of the COVID-19 vaccines. DISCUSSION/CONCLUSION: The successful expansion of laboratory testing capacity was instrumental in the control and management of COVID-19 cases and critical in the implementation of public response strategies, including restrictions on gathering. Laboratory testing also facilitated the movement of humanitarian agencies and delivery of aid and enabled hundreds of thousands of Yemeni nationals to travel internationally. By virtue of these outcomes, the impact of laboratory strengthening activities was thus felt in the health sector and beyond.

WHO's Investigations and Studies, Unity Studies: A global initiative creating equitable opportunities for enhanced surveillance, operational research, capacity building, and global knowledge sharing.

The World Health Organization's Unity Studies global initiative provides a generic preparedness and readiness framework for conducting detailed investigations and epidemiological studies critical for the early and ongoing assessment of emerging respiratory pathogens of pandemic potential. During the COVID-19 pandemic, the initiative produced standardized investigation protocols and supported Member States to generate robust and comparable data to inform public health decision making. The subsequent iteration of the initiative is being implemented to develop revised and new investigation protocols, implementation toolkits and work to build a sustainable global network of sites, enabling the global community to be better prepared for the next emerging respiratory pathogen with epidemic or pandemic potential.

2009 Pandemic influenza A virus subtype H1N1 in Morocco, 2009-2010: epidemiology, transmissibility, and factors associated with fatal cases.

BACKGROUND: Following the emergence of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) in the United States and Mexico in April 2009, A(H1N1)pdm09 spread rapidly all over the world. There is a dearth of information about the epidemiology of A(H1N1)pdm09 in Africa, including Morocco. We describe the epidemiologic characteristics of the A(H1N1)pdm09 epidemic in Morocco during 2009-2010, including transmissibility and risk factors associated with fatal disease. METHODS: We implemented influenza surveillance for patients presenting with influenza-like illness (ILI) at 136 private and public clinics for patients with severe acute respiratory illness (SARI) at 16 regional public hospitals from June 2009 through February 2010. Respiratory samples and structured questionnaires were collected from all enrolled patients, and samples were tested by real-time reverse-transcription polymerase chain reaction for influenza viruses. We estimated the risk factors associated with fatal disease as well as the basic reproduction number (R(0)) and the serial interval of the pandemic virus. RESULTS: From June 2009 through February 2010, we obtained 3937 specimens, of which 1452 tested positive for influenza virus. Of these, 1398 (96%) were A(H1N1)pdm09. Forty percent of specimens from ILI cases (1056 of 2646) and 27% from SARI cases (342 of 1291) were positive for A(H1N1)pdm09. Sixty-four deaths occurred among laboratory-confirmed A(H1N1)pdm09 SARI cases. Among these cases, those who had hypertension (age-adjusted odd ratio [aOR], 28.2; 95% confidence interval [CI], 2.0-398.7), had neurological disorders (aOR, 7.5; 95% CI, 1.5-36.4), or were obese (aOR, 7.1; 95% CI, 1.6-31.1), as well as women of gestational age who were pregnant (aOR, 2.5; 95% CI, 1.1-5.6), were at increased risk of death. Across the country, elevated numbers of locally acquired infections were detected 4 months after the detection of the first laboratory-confirmed case and coincided with the expected influenza season (October-January) in Morocco. We obtained an R(0) estimate of 1.44 (95% CI, 1.32-1.56) and a mean serial interval (±SD) of 2.3 ± 1.4 days (95% CI, 1.6-3.0). CONCLUSION: Widespread but delayed community transmission of A(H1N1)pdm09 occurred in Morocco in 2009, and A(H1N1)pdm09 became the dominant influenza virus subtype during the 2009-2010 influenza season. The transmissibility characteristics were similar to those observed in other countries.

Influenza surveillance in 15 countries in Africa, 2006-2010.

BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Garden cress gum and maltodextrin as microencapsulation coats for entrapment of garden cress phenolic-rich extract: improved thermal stability, storage stability, antioxidant and antibacterial activities.

The obtained garden cress 6-day sprouts phenolic-rich extract (GCSP) contained efficient health-promoting antioxidant-phenolic compounds. To improve the stability, bioavailability, and functional properties of these valuable phenolic compounds, GCSP was encapsulated by freeze-drying technique using different ratios of garden cress gum (GG) and maltodextrin (M) in the absence and presence of sonication (S). The prepared S/GG-microcapsule retained the highest phenolic content (95%), antioxidant activity (141.6%), and encapsulation efficiency (98.2%). It displayed the highest bio-accessibility of GCSP-phenolic compounds in simulated intestine fluid (87%) and demonstrated the greatest storage-stability at 40 °C for 60 days. S/GG-microcapsule possessed better physical properties including moisture, solubility, swelling, and morphological structures using SEM. The main spectral features, crosslinking, and improved thermal stability were demonstrated for S/GG-microcapsule using FTIR and thermogravimetric analyses. S/GG-microcapsule demonstrated much greater antibacterial activity than GCSP against pathogenic bacteria. S/GG-microcapsule can be added to different food products to improve their antioxidant and antibacterial properties.

Statistical optimization, characterization, antioxidant and antibacterial properties of silver nanoparticle biosynthesized by saw palmetto seed phenolic extract.

On the global market, silver nanoparticles (Ag-NPs) are in high demand for their various applications in biomedicine, material engineering, and consumer products. This study highlighted the biosynthesis of the Ag-NPs using saw palmetto seed phenolic extract (SPS-phenolic extract), which contained vital antioxidant-phenolic compounds. Herein, central composite statistical design, response surface methodology, and sixteen runs were conducted to optimize Ag-NPs biosynthesis conditions for maximizing the production of Ag-NPs and their phenolic content. The best-produced SPS-Ag-NPs showed a surface plasmon resonance peak at 460 nm and nano-spherical sizes ranging from 11.17 to 38.32 nm using the UV spectrum analysis and TEM images, respectively. The produced SPS-Ag-NPs displayed a high negative zeta-potential value (- 32.8 mV) demonstrating their high stability. The FTIR analysis demonstrated that SPS-phenolic compounds were involved in sliver bio-reduction and in stabilizing, capping, and preventing Ag-NP aggregation. The thermogravimetric investigation revealed that the produced SPS-Ag-NPs have remarkable thermal stability. The produced SPS-Ag-NP exceeded total antioxidant activity (13.8 µmol Trolox equivalent) more than the SPS-phenolic extract (12.0 µmol Trolox equivalent). The biosynthesized SPS-Ag-NPs exhibited noticeably better antibacterial activity against multidrug-resistant Gram-negative E. coli and Gram-positive S. aureus compared to SPS-phenolic extract. Hence, the bio-synthesized SPS-Ag-NPs demonstrated great potential for use in biomedical and antimicrobial applications.

Key aspects defining the development and implementation of a regional genomic surveillance strategy for the Eastern Mediterranean Region.

The COVID-19 pandemic highlighted the critical role of pathogen sequencing in making informed public health decisions. Initially, the Eastern Mediterranean Region faced limitations in sequencing capacity. However, with robust WHO and stakeholder support, the situation significantly improved. By 2022, COVID-19 sequencing was underway in 22 out of 23 regional countries, with varying throughput and capacity. Notably, three genomic hubs were established in Oman, UAE, and Morocco, playing a key role in providing expanded genomics training and support across the region. While primarily for COVID-19 surveillance, this sequencing capacity offers an opportunity to integrate genomic surveillance into existing networks. This integration can enable early detection and response to high-threat pathogens with pandemic potential. To advance this, WHO/EMRO collaborated with stakeholders to formulate the Eastern Mediterranean Regional Genomic Surveillance Strategy for Emerging Pathogens of Pandemic Concern. Consultative meetings with regional and international genomic surveillance experts identified strategy focal points, key partners, priority pathogens, and implementation steps. As the strategy awaits member states' ratification in Q4 2023, this manuscript outlines pivotal facets defined by member states and the strategic document's key deliverables and opportunities. These efforts aim to yield a substantial positive impact within the region.

Monitoring the quality of SARS-CoV-2 virus detection in molecular diagnostic laboratories in the Eastern Mediterranean Region during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic placed unprecedented stress on laboratories in the Eastern Mediterranean Region. Building on existing capacity for influenza diagnostics, countries introduced COVID-19 diagnostic support to ~100% regional coverage. A key challenge during the expansion was maintaining quality testing in laboratories, ensuring that correct results were shared with medical facilities. METHODS: WHO organized two rounds of independently monitored severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) external quality assurance programs (EQAP). The Public Health Laboratory (PHL) division of WHO supplied external quality assurance (EQA) panels, from the Royal College of Pathologists of Australasia Quality Assurance Programme (RCPAQAP) Australia to laboratories not enrolled in recurring Global Influenza Surveillance and Response System (GISRS) quality assurance programs, in which national influenza centers routinely participate. RESULTS: Fifteen and 14 countries participated in PHL/EQAP for SARS-CoV-2 between 2020 and 2022. Concordance was consistent between rounds, reaching 96.4% and 89.9%. A separate assessment of GISRS/EQAP to national-level laboratories identified high levels of response and concordance for SARS-CoV-2 (100% response, 93% concordance), which was reduced for influenza (50% response rate, 80% concordance), reflecting the challenge of prioritizing pathogens during outbreaks. CONCLUSION: The proliferation of laboratories in response to COVID-19 was a success story from the pandemic. However, monitoring the quality of laboratories was challenging via existing EQAP. The addition of PHL/EQAP provided a mechanism to monitor performance of laboratories that were not designated as national influenza centers. While a high proportion of laboratories attained good results, continual emphasis on quality and enrollment in EQAP is key to ensuring sustainability of laboratory testing in future.

Antioxidant system of garden cress sprouts for using in bio-monitor of cadmium and lead contamination.

Based on garden cress significantly used for phytoremediation, the antioxidant system included antioxidant-phenolic compounds and antioxidant-enzymes of 6-day-garden cress sprouts (GCS) were assessed as potential bio-indicators for cadmium (Cd) and lead (Pb) contamination. Total phenolic and flavonoid contents of GCS germinated under Cd and Pb treatments (25-150 mg kg-1) gradually increased with increasing concentration of metals and peaked by 2.0, 2.6, and 2.5, 2.3 folds at 150 mg kg-1, respectively. By using DPPH, ABTS, and PMC antioxidant assays, the total antioxidant activity of phenolic compounds of GCS increased 6.1, 13.0, and 5.8-fold for Cd and 5.9, 14.6, and 8.2-fold for Pb at 150 mg kg-1, respectively. The antioxidant enzymes of GCS (POD, CAT, GR, and GST) were significantly activated in response to Cd and Pb stress, and two new electrophoretic POD bands were detected. GCS was absorbed 19.0% and 21.3% of Cd and Pb at 150 mg metal kg-1, respectively. In conclusion, the approaches of the antioxidant defense system of GSC could potentially be used as bio-indicator for monitoring Cd and Pb contamination in a short time of germination process.

The Impact of interferon lambda 3 Polymorphism on Hepato-Cellular Carcinoma Progression in Hepatitis C Virus Patients: Treatment-Naïve and Experienced.

OBJECTIVES: In this study, we investigated the association between the IFN-λ3 rs12979860 single nucleotide polymorphism (SNP) and the transition from late fibrosis to HCC in Egyptian HCV-chronically infected patients. METHODS: The rs12979860 SNP was genotyped using real-time PCR in DNA from the whole blood of healthy subjects (n=60) and HCV patient   s (n=342). We stratified the patients into (1) treatment-naïve patients (n=218) with advanced fibrosis (F2-F4, n=123) and HCC (n=95 Treatment-experienced patients (n=124)  who received SOF-based therapy for 12 weeks and achieved SVR (SVR12). DAA-treated patients were divided into 2 groups: group I (n=63) included patients with advanced hepatic fibrosis (F2-F4) who did not develop HCC within a year after treatment, and group II (n=61) included patients who were free of focal hepatic lesions before starting DAA therapy but developed HCC within a year. RESULTS: Our results demonstrated that treatment-naïve patients with the CT/TT genotypes and the T allele were more likely to have HCC (odds ratio 3.1, 95% CI 1.44-6.71, P = 0.003 and odds ratio 1.89, 95% CI 1.28-2.76, P = 0.001, respectively). Binary regression analysis defined 3 independent predictors associated with HCC development: age (odds ratio 1.039, 95% CI 1.004-1.076, P = 0.028), alanine aminotransferase (odds ratio 1.008, 95% CI 1.002-1.015, P = 0.010), and rs12979860 (odds ratio 3.65, 95% CI 1.484-8.969, P = 0.005). CONCLUSIONS: However, the rs12979860 SNP did not show any correlation with the progression of HCC post-treatment. Despite the debate on the contribution of IFN-λ3 rs12979860 to susceptibility to HCV-related HCC, our data confirm the role of this SNP in this context.