HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion.

Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 cold induction remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons. We found that RBM3 mRNA and protein levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being the strongest positive regulator. Splicing analysis revealed that moderate hypothermia significantly represses the inclusion of a poison exon, which, when retained, targets the mRNA for nonsense-mediated decay. Importantly, we show that HNRNPH1 mediates this cold-dependent exon skipping via its thermosensitive interaction with a G-rich motif within the poison exon. Our study provides novel mechanistic insights into the regulation of RBM3 and provides further targets for neuroprotective therapeutic strategies.

The Role of Maternal Preconception Adiposity in Human Offspring Sex and Sex Ratio.

We evaluated relationships between preconception adiposity and human offspring sex and sex ratio. Using data from a prospective preconception cohort nested within a randomized controlled trial based at 4 US clinical sites (2006-2012), we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for male:female sex ratio, and log-identity regression to estimate risk differences (RDs) and 95% CIs for male and female livebirth according to preconception adiposity measures. Inverse-probability weights accounted for potential selection bias. Among 603 women attempting pregnancy, there were meaningful reductions in sex ratio for the highest category of each adiposity measure. The lowest sex ratios were observed for obesity (body mass index of ≥30, calculated as weight (kg)/height (m)2, OR = 0.48, 95% CI: 0.26, 0.88) relative to normal body mass index, and the top tertiles (tertile 3) of serum leptin (OR = 0.50, 95% CI: 0.32, 0.80) and skinfold measurements (OR = 0.50, 95% CI: 0.32, 0.79) relative to the lowest tertiles. Reductions were driven by 11-15 fewer male livebirths per 100 women (for obesity, RD = -15, 95% CI: -23, -6.7; for leptin tertile 3, RD = -11, 95% CI: -20, -3.2; and for skinfolds tertile 3, RD = -11, 95% CI: -19, -3.3). We found that relationships between preconception adiposity measures and reduced sex ratio were driven by a reduction in male births.

Variability in Sleep Duration and Biomarkers of Cardiovascular Disease Across the Menstrual Cycle.

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44 years. The BioCycle study (New York, 2005-2007) collected cardiovascular biomarkers (serum high- and low-density lipoprotein (HDL, LDL), total cholesterol, triglycerides, and C-reactive protein (CRP)) at key time points along the menstrual cycle (follicular, ovulatory, and luteal phases). Women also recorded sleep duration in daily diaries. From these data, we computed L-moments, robust versions of location, dispersion, skewness, and kurtosis. We fitted linear mixed models with random intercepts and inverse probability weighting to estimate associations between sleep variability and cardiovascular biomarkers, accounting for demographic, lifestyle, health, and reproductive factors. Sleep dispersion (any deviation from mean duration) was associated with lower mean LDL for nonshift workers and non-White women. Skewed sleep duration was associated with higher mean CRP and lower mean total cholesterol. Sleep durations with extreme short and long bouts (kurtosis) were associated with a lower mean HDL, but not mean CRP, LDL, or triglycerides. Sleep duration modified associations between sleep dispersion and LDL, HDL, and total cholesterol. Even in young and healthy women, sleep duration variability could influence cardiovascular health.

Writing Support Group for Medical School Faculty-A Simple Way to Do It.

Problem: Writing for publication is a core activity for many medical school faculty, but faculty report numerous challenges to publication. To help address these challenges, some medical schools establish writing support programs, but those programs are often resource-intensive, involving didactic courses, accountability groups, formal mentorships, and even assistance from professional writers. Not all medical schools, however, provide resources for such programs, and many faculty members, especially clinicians, lack time needed to participate. Furthermore, success of these programs is typically judged by the total number of papers published. However, many clinicians would judge success as publication of the occasional papers they decide to write, not the total number of papers they or the group publish. With these issues in mind, we established a low-resource writing program focused on individual acceptance rates rather than total publications. Intervention: Our writing program is an informal group that meets monthly. Members bring their ideas for papers and drafts of papers, and other members provide critique and suggestions for improvement. Members then revise their papers to address that critique prior to journal submission. There are no formal or assigned mentors, courses, lectures, or writing assistants. Context: The program takes place in our family medicine department, in which faculty have various roles. Some group members are clinician-educators seeking to publish occasional clinical reviews or research articles; others are PhDs seeking to publish on aspects of their work. Impact: During the six years of the program, 86% of papers reviewed by the group were accepted for publication and 94% of those were accepted by the journal to which they were first submitted. Publication success rate of individual members averaged 79%. This exceeds the 30-40% acceptance rate for scholarly journals worldwide. Group members published an average of 5.2 papers per member, with some publishing as few as 2-3 papers and others as many as 10-11. Lessons Learned: An informal, low-resource writing program in medical school departments can help faculty reach their publication goals. We found that members were satisfied by having the group help them publish whatever number of papers they decided to write. The program's simple, informal approach fostered a culture of respectful and collegial interactions, in which members learned to depend on and accept critiques from colleagues. Finally, an unexpected benefit of our program resulted from membership of both clinicians and non-clinicians. This provided feedback from individuals with different perspectives, which enhanced development of manuscripts.

Novel magnesium-copper hybrid nanomaterials for management of bacterial spot of tomato.

Bacterial spot of tomato (BST), predominantly caused by Xanthomonas perforans (Xp) in Florida, is one of the most devastating diseases in hot, humid environments. Bacterial resistance to copper-based bactericides and antibiotics makes disease management extremely challenging. This necessitates alternative solutions to manage the disease. In this study, we used two novel hybrid copper and magnesium nanomaterials noted as magnesium double-coated (Mg-Db) and magnesium-copper (Mg-Cu), to manage BST. In in vitro experiments, no viable cells were recovered following 4 h exposure to 500 µg/ml of both Mg-Db and Mg-Cu, while 100 and 200 µg/ml required 24 h of exposure for complete inhibition. In viability assay using live/dead cell straining method and epifluorescence microscopy, copper tolerant Xp cells were killed within 4 h by both Mg-Cu and Mg-Db nanomaterials at 500 µg/ml, but not by copper hydroxide (Kocide 3000). In the greenhouse, Mg-Db and Mg-Cu at 100-500 µg/ml significantly reduced BST severity compared to micron-sized commercial Cu bactericide Kocide 3000 and the growers' standard (copper hydroxide + mancozeb) (P < 0.05). In field studies, Mg-Db and Mg-Cu nanomaterials significantly reduced disease severity in two out for field trials. Mg-Db at 500 µg/ml reduced BST severity by 34% compared to the non-treated control without affecting yield in Fall, 2020. The use of hybrid nanomaterials at the highest concentrations (500 µg/ml) used in the field experiments can reduce copper use by 90% compared to the growers' standard. In addition, there was no phytotoxicity observed with the use of hybrid nanomaterials in the field. These results suggest the potential of novel magnesium-copper based hybrid nanomaterials to manage copper-tolerant bacterial pathogens.

Microbiology of septic arthritis in young Auckland children.

BACKGROUND: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known. METHODS: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management. RESULTS: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin. CONCLUSIONS: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae.

Is Alcohol Consumption Associated With Risk of Early Menopause?

Earlier age at menopause is associated with increased long-term health risks. Moderate alcohol intake has been suggested to delay menopause onset, but it is unknown whether alcohol subtypes are associated with early menopause onset at age 45 years. Therefore, we aimed to evaluate risk of early natural menopause among 107,817 members of the Nurses' Health Study II who were followed from 1989 to 2011. Alcohol consumption overall and by subtypes, including beer, red wine, white wine, and liquor, was assessed throughout follow-up. We estimated hazard ratios in multivariable models that were adjusted for age, body mass index, parity, smoking, and other potential confounders. Women who reported moderate current alcohol consumption had lower risks of early menopause than did nondrinkers. Those who reported consuming 10.0-14.9 g/day had a lower risk of early menopause than did nondrinkers (hazard ratio = 0.81, 95% confidence interval: 0.68, 0.97). Among specific beverages, evidence of lower early menopause risk was confined to consumption of white wine and potentially red wine and liquor, but not to beer. Data from this large prospective study suggest a weak association of moderate alcohol intake with lower risk of early menopause, which was most pronounced for consumption of white and red wine and liquor. High consumption was not related to lower risk of early menopause.

Magnesium Oxide Nanomaterial, an Alternative for Commercial Copper Bactericides: Field-Scale Tomato Bacterial Spot Disease Management and Total and Bioavailable Metal Accumulation in Soil.

Copper (Cu) is the most extensively used bactericide worldwide in many agricultural production systems. However, intensive application of Cu bactericide have increased the selection pressure toward Cu-tolerant pathogens, including Xanthomonas perforans, the causal agent of tomato bacterial spot. However, alternatives for Cu bactericides are limited and have many drawbacks including plant damage and inconsistent effectiveness under field conditions. Also, potential ecological risk on nontarget organisms exposed to field runoff containing Cu is high. However, due to lack of alternatives for Cu, it is still widely used in tomato and other crops around the world in both conventional and organic production systems. In this study, a Cu-tolerant X. perforans strain GEV485, which can tolerate eight tested commercial Cu bactericides, was used in all the field trials to evaluate the efficacy of MgO nanomaterial. Four field experiments were conducted to evaluate the impact of intensive application of MgO nanomaterial on tomato bacterial spot disease severity, and one field experiment was conducted to study the impact of soil accumulation of total and bioavailable Cu, Mg, Mn, and Zn. In the first two field experiments, twice-weekly applications of 200 µg/mL MgO significantly reduced disease severity by 29-38% less in comparison to a conventional Cu bactericide Kocide 3000 and 19-30% less in comparison to the water control applied at the same frequency (p = 0.05). The disease severity on MgO twice-weekly was 12-32% less than Kocide 3000 + Mancozeb treatment. Single weekly applications of MgO had 13-19% higher disease severity than twice weekly application of MgO. In the second set of two field trials, twice-weekly applications of MgO at 1000 µg/mL significantly reduced disease severity by 32-40% in comparison to water control applied at the same frequency (p = 0.05). There was no negative yield impact in any of the trials. The third field experiment demonstrated that application of MgO did not result in significant accumulation of total and bioavailable Mg, Mn, Cu, or Zn in the root-associated soil and in soil farther away from the production bed compared to the water control. However, Cu bactericide contributed to significantly higher Mn, Cu, and Zn accumulation in the soil compared to water control (p = 0.05). This study demonstrates that MgO nanomaterial could be an alternative for Cu bactericide and have potential in reducing risks associated with development of tolerant strains and for reducing Cu load in the environment.

Photoconductive arrays on insulating substrates for high-field terahertz generation.

We report on the design, fabrication and characterisation of large-area photoconductive THz array structures, consisting of a thin LT-GaAs active region transferred to an insulating substrate using a wafer-scale bonding process. The electrically insulating, transparent substrate reduces the parasitic currents in the devices, allowing peak THz-fields as high as 120 kV cm-1 to be generated over a bandwidth >5 THz. These results are achieved using lower pulse energies than demanded by conventional photoconductive arrays and other popular methods of generating high-field THz radiation. Two device sizes are fully characterised and the emission properties are compared to generation by optical rectification in ZnTe. The device can be operated in an optically saturated regime in order to suppress laser noise.

Community-acquired invasive Staphylococcus aureus: Uncovering disparities and the burden of disease in Auckland children.

AIM: Staphylococcus aureus (SA) causes serious invasive disease in children. Large studies have measured the incidence of SA bacteraemia, but there is less information on the total burden of community-acquired invasive SA (iSA) in children. METHODS: A retrospective, cross-sectional analysis of Auckland resident children aged 0-14 years who were hospitalised with iSA between 2011 and 2015 was performed. Laboratory databases and SA-related international classification of diseases 10 discharge codes were searched to identify community-onset cases with SA isolated from a normally sterile site. Clinical records and coroner's reports were reviewed to determine clinical syndromes and exclude nosocomial infections. RESULTS: A total of 295 children with iSA were identified. The average annual incidence of iSA was 18.6 per 100 000 - for Pacific populations 44.3 per 100 000, Maori 24.3 per 100 000 and New Zealand European and other 8.8 per 100 000; 68% had bacteraemia. The incidence of iSA for Pacific infants was 10 times greater than non-Maori/non-Pacific (113.4/100 000 population vs. 11.8/100 000). Multivariate analysis found a higher risk of admission in Pacific children, males and those living in areas of high deprivation. Thirty-two patients (10.8%) were admitted to the intensive care unit; risk was higher in infants, Pacific children and those with respiratory infection (Relative Risk (RR) 12.2, 95% confidence interval (CI) 5.7-26.4) and multifocal (RR 6.9, 95% CI 3.4-13.8) and endovascular disease (RR 8.9, 95% CI 3.9-20.6). All deaths (n = 7) had respiratory infections, and four were patients <1 year of age. CONCLUSIONS: Studies investigating SA bacteraemia alone significantly underestimate the total burden of iSA disease. There are marked ethnic and socio-economic disparities in iSA disease among Auckland children. Pacific infants are at the highest risk.

Correlates of At-Risk and Problem Gambling Among Veterans in Massachusetts.

Few studies have examined problem gambling among veterans and, of those studies, there are conflicting conclusions surrounding correlates of problem gambling in veterans. Our study aims to assess problem gambling prevalence among veterans using non-Veterans Affairs data and to evaluate correlates of problem gambling among veterans in a general population sample. We obtained a probability sample of adult Massachusetts residents using address based sampling in 2013-2014. Participants completed a questionnaire on demographics, veteran status, and gambling behaviors and motivations. We identified n = 129 problem gamblers from a sample of n = 9578 participants. Of the problem gamblers who had veteran status information, 20.6% were veterans. Due to sample size limitations, we analyzed veteran problem and at-risk gamblers compared to veteran recreational gamblers. Having friends and family members engaged in gambling and engaging in more gambling formats were significantly, positively associated with veteran problem and at-risk gambler status. Participating in raffles in the past year was associated with lower odds of being a veteran problem and at-risk gambler compared to veteran recreational gamblers (OR 0.31, 95% CI 0.18-0.52). These discriminators of at-risk and problem gambling may be useful in developing clinical treatment approaches for veteran problem gamblers. Future studies should focus on changes in the prevalence of veteran problem gambling and additional correlates that may better capture social support domains and gambling activity among veterans.

An Improved Crop Scouting Technique Incorporating Unmanned Aerial Vehicle-Assisted Multispectral Crop Imaging into Conventional Scouting Practice for Gummy Stem Blight in Watermelon.

Multispectral imaging is increasingly used in specialty crops, but its benefits in assessment of disease severity and improvements in conventional scouting practice are unknown. Multispectral imaging was conducted using an unmanned aerial vehicle (UAV), and data were analyzed for five flights from Florida and Georgia commercial watermelon fields in 2017. The fields were rated for disease incidence and severity by extension agents and plant pathologists at randomized locations (i.e., conventional scouting) followed by ratings at locations that were identified by differences in normalized difference vegetation index (NDVI) and stress index (i.e., UAV-assisted scouting). Diseases identified by the scouts included gummy stem blight, anthracnose, Fusarium wilt, Phytophthora fruit rot, Alternaria leaf spot, and cucurbit leaf crumple disease. Disease incidence and severity ratings were significantly different between conventional and UAV-assisted scouting (P < 0.01, Bhapkar/exact test). Higher severity ratings of 4 and 5 on a scale of 1 to 5 from no disease to complete loss of the canopy were more consistent after the scouts used the multispectral images in determining sampling locations. The UAV-assisted scouting locations had significantly lower green, red, and red edge NDVI values and higher stress index values than the conventional scouting areas (P < 0.05, ANOVA/Tukey), and this corresponded to areas with higher disease severity. Conventional scouting involving human evaluation remains necessary for disease validation. Multispectral imagery improved watermelon field scouting owing to increased ability to identify disease foci and areas of concern more rapidly than conventional scouting practices with early detection of diseases 20% more often using UAV-assisted scouting.

Transgenic Expression of EFR and Bs2 Genes for Field Management of Bacterial Wilt and Bacterial Spot of Tomato.

Field trials were conducted at two locations in Florida to evaluate transgenic tomato expressing the ELONGATION FACTOR TU RECEPTOR (EFR) gene from Arabidopsis thaliana, the Bs2 gene from pepper, or both Bs2 and EFR (Bs2/EFR) for managing bacterial wilt caused by Ralstonia solanacearum and bacterial spot caused by Xanthomonas perforans. Expression of EFR or Bs2/EFR in the susceptible genotype Fla. 8000 significantly reduced bacterial wilt incidence (50 to 100%) and increased total yield (57 to 114%) relative to lines expressing only Bs2 or the nontransformed Fla. 8000 control, although the marketable yield was not significantly affected. Following harvest, surviving symptomatic and nonsymptomatic plants were assessed for colonization by R. solanacearum. There were no significant differences in the population at the lower stem. Interestingly, in the middle stem, no bacteria could be recovered from EFR or Bs2/EFR lines but viable bacterial populations were recovered from Bs2 and nontransformed control lines at 102 to 105 CFU/g of stem tissue. In growth-chamber experiments, the EFR transgenic tomato lines were found to be effective against seven different R. solanacearum strains isolated from the southeastern United States, indicating utility across the southeastern United States. In all of the bacterial spot trials, EFR and Bs2/EFR lines had significantly reduced disease severity (22 to 98%) compared with the Fla. 8000 control. The marketable and total yield of Bs2/EFR were significantly higher (43 to 170%) than Fla. 8000 control in three of four field trials. These results demonstrate for the first time the potential of using the EFR gene for field management of bacterial wilt and bacterial spot diseases of tomato.

Terahertz generation mechanism in nano-grating electrode photomixers on Fe-doped InGaAsP.

We report the generation mechanism associated with nano-grating electrode photomixers fabricated on Fe-doped InGaAsP substrates. Two different emitter designs incorporating nano-gratings coupled to the same broadband antenna were characterized in a continuous-wave terahertz (THz) frequency system employing telecommunications wavelength lasers for generation and coherent detection. The current-voltage characteristics and THz emission bandwidth of the emitters is compared for different bias polarities and optical polarisations. The THz output from the emitters is also mapped as a function of the position of the laser excitation spot for both continuous-wave and pulsed excitation. This mapping, together with full-wave simulations of the structures, confirms the generation mechanism to be due to an enhanced optical electric field at the grating tips resulting in increased optical absorption, coinciding with a concentration of the electrostatic field.

Foliar Applications of Acibenzolar-S-Methyl Negatively Affect the Yield of Grafted Tomatoes in Fields Infested with Ralstonia solanacearum.

Three field experiments were conducted in Florida from 2012-2014 to assess the impact of acibenzolar-S-methyl (ASM), a systemic acquired-resistance inducer, applied as foliar spray or through drip-irrigation lines, on bacterial wilt incidence and yield of grafted tomatoes. The experiments were conducted in a field with race 1, biovar 1 strain of Ralstonia solanacearum, causal agent of tomato bacterial wilt. In all three experiments, the susceptible tomato variety BHN 602, grafted onto a resistant rootstock BHN 998, was compared with nongrafted BHN 602, treated with or without foliar applications of ASM and with grafted plants treated with foliar applications of ASM. In two experiments, an additional treatment of drip applications of ASM on grafted and nongrafted plants was evaluated. Grafting alone or in combination with drip applications of ASM (178.6 µM) significantly reduced disease incidence and increased total marketable yield relative to nongrafted treatments. There were no significant differences between grafted plants with or without drip ASM applications in terms of bacterial wilt incidence or total marketable yield. However, we demonstrate for the first time that foliar ASM applications on grafted plants negatively affects the total marketable yield compared with drip ASM applications on grafted plants or nontreated grafted control.

Mediation Analysis of Hepatitis B and C in Relation to Hepatocellular Carcinoma Risk.

BACKGROUND: Hepatitis B and C viruses are well-established risk factors for hepatocellular carcinoma (HCC) but their coordinated etiologic mechanism remains unclear. We aimed to assess the mediation effect of the two viruses on HCC risk. METHODS: We conducted a prospective cohort study in Taiwan (R.E.V.E.A.L.-Hepatitis B Virus study), which included 3,851 participants seropositive for hepatitis B surface antigen and 278 incident HCC cases. Serum samples at enrollment or follow-up were tested for seromarkers and viral load of hepatitis B (HBV) and C (HCV). Mediation analyses for HCC risk were performed using Cox proportional hazards and linear regression models. RESULTS: Among participants with chronic hepatitis B, the direct effect of anti-HCV serostatus (positive vs. negative) independent of HBV viral load was associated with increased risk of HCC with a hazard ratio (HR) of 2.5 (95% confidence interval [CI] = 1.7, 3.6), and the indirect effect mediated through suppressing HBV viral load decreased the HCC risk with an HR of 0.75 (95% CI = 0.67, 0.84). Opposite effects led to an attenuated marginal effect with an HR of 1.7 (95% CI = 1.2, 2.5). For an increase in HCV viral load from 800 to 404,000 IU/ml (minimum to median viral level), the HRs were 1.6 (95% CI = 1.2, 2.0) for the direct effect, 0.78 (95% CI = 0.72, 0.85) for the indirect effect, and 1.1 (95% CI = 0.89, 1.5) for the marginal effect. CONCLUSION: The results support a suppressive effect of HCV on HCC risk mediated through HBV viral load and an adverse direct effect.

Free-space terahertz radiation from a LT-GaAs-on-quartz large-area photoconductive emitter.

We report on large-area photoconductive terahertz (THz) emitters with a low-temperature-grown GaAs (LT-GaAs) active layer fabricated on quartz substrates using a lift-off transfer process. These devices are compared to the same LT-GaAs emitters when fabricated on the growth substrate. We find that the transferred devices show higher optical-to-THz conversion efficiencies and significantly larger breakdown fields, which we attribute to reduced parasitic current in the substrate. Through these improvements, we demonstrate a factor of ~8 increase in emitted THz field strength at the maximum operating voltage. In addition we find improved performance when these devices are used for photoconductive detection, which we explain through a combination of reduced parasitic substrate currents and reduced space-charge build-up in the device.

Mediation effect of hepatitis B and C on mortality.

Hepatitis B (HBV) and C (HCV) viruses cause many liver diseases. To move beyond statistical interaction, we aimed to assess the coordinated effect of the two viruses on mortality using mediation analyses. A prospective cohort study of 3837 residents in Taiwan examined participants seropositive for hepatitis B, of which 181 subjects (4.7 %) were co-infected by HCV and 589 died during follow-up. Mediation analyses for cause-specific mortality were performed using Cox proportional hazards model. Follow-up HBV viral load was inversely correlated with baseline HCV viral load (r(2) = -0.074; P < 0.001). For HCV serum viral load increasing from 800 to 404,000 IU/mL (minimum to median) at baseline, the effect of HCV mediated through HBV viral load decreased the all-cause mortality with a hazard ratio (HR) of 0.89 (95 % confidence interval (CI) 0.85, 0.94; P < 0.001), and the effect independent of HBV viral load had an opposite HR of 1.25 (95 % CI 0.98, 1.60; P = 0.08). The protective mediation effects of HCV viral load through HBV DNA level were observed in mortality from causes specific to liver-related diseases and liver cancer, but not in that from non-liver-related diseases. Our findings suggest a suppressive effect of HCV on mortality mediated through decreasing HBV viral load.