Using National Healthcare Safety Network data, an interrupted time series of intravenous antimicrobial starts (IVAS) among hemodialysis patients was performed. Annual adjusted rates decreased by 6.64% (January 2012-March 2020) and then further decreased by 8.91% until December 2021. IVAS incidence trends have decreased since 2012, including during the early COVID-19 pandemic.

BACKGROUND: Globally, opioid use remains a major public health problem. In 2019, 480,000 deaths were related to opioid use. Locally, mortality from opioid-involved overdose is high among Illinois residents, with 83 % of ∼4000 overdose deaths during 2022 involving opioids. Treatment for opioid use disorder with buprenorphine, methadone, and naltrexone is approved, safe, and effective. However, significant barriers to treatment remain for many persons. METHODS: In response to new prescribing policy flexibilities, in May 2022, the Chicago Department of Public Health and the Substance Use Prevention and Recovery Division of the Illinois Department of Human Services partnered with a statewide opioid treatment provider, Family Guidance Centers. The partnership started an immediate opioid use disorder treatment helpline program. We performed a descriptive analysis using aggregate data from all calls for assistance with substance use received by the Illinois Helpline during May 9, 2022-March 7, 2024. RESULTS: A total of 2649 unique calls were made to the helpline from persons seeking assistance with substance use, and 1698 unique callers were connected to Family Guidance Centers for treatment initiation. Most callers were prescribed buprenorphine by telemedicine, followed by methadone during in-person treatment. In total, 1515 (89.2 %) of 1698 callers with opioid use disorder were initiated on buprenorphine or methadone through the program. CONCLUSION: A state-wide low-barrier access to medications by telemedicine program is an effective treatment model for the initiation of medications for opioid use disorder.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected.

The COVID-19 pandemic has demonstrated a clear need for high-throughput, multiplexed, and sensitive assays for detecting SARS-CoV-2 and other respiratory viruses as well as their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic CARMEN (mCARMEN), that combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel (RVP) to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.

We investigated cross-sectional associations between children's neurodevelopment and their gut microbiota composition. Study children (36 months of age) lived in rural China (n = 46). Neurodevelopment was assessed using the Bayley Scales of Infant Development, 2nd Edition, yielding the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Children's gut microbiota was assessed using 16S rRNA gene profiling. Microbial diversity was characterized using alpha diversity patterns. Additionally, 3 coabundance factors were determined for the 25 most abundant taxa. Multivariable linear regression models were constructed to examine the relationships between Bayley scores (MDI and PDI) and children's gut microbiota. In adjusted models, MDI and PDI scores were not associated with alpha diversity indices. However, in adjusted models, MDI and PDI scores were positively associated with the first coabundance factor, which captured positive loadings for the genera Faecalibacterium, Sutterella, and Clostridium cluster XIVa. For an interquartile range increase in the first coabundance factor, MDI scores increased by 3.9 points [95% confidence interval (CI): 0, 7.7], while PDI scores increased by 8.6 points (95% CI 3.1, 14). Our results highlight the potential for gut microbial compositional characteristics to be important correlates of children's Bayley Scales performance at 36 months of age.

Protecting health care workers from COVID-19 remains a priority during the ongoing pandemic. Accurate assessment of the risk for infection among health care workers is important in determining the effectiveness of infection control plans. In late March 2020, a total of 591 U.S. Army personnel from three units were deployed from areas in which COVID-19 incidence was low to the Javits New York Medical Station (JMS), a 452-bed Federal Emergency Management Agency Federal Medical Station in New York City (NYC), to provide care to COVID-19 patients. Army personnel followed a rigorous infection control plan and remained largely isolated from the surrounding community while in NYC. During April 3–25, a total of 1,095 COVID-19 patients were admitted from NYC area hospitals to the JMS ward or intensive care unit (ICU). A cross-sectional study of the prevalence of SARS-CoV-2 infection among 336 active duty soldiers enrolled in a prevalence study identified an infection rate of 1.7% overall and 0.9% in the 223 (66.4%) enrolled soldiers who provided direct care to COVID-19 patients. A well-designed and well-implemented infection control plan can mitigate the risk for SARS-CoV-2, the virus that causes COVID-19, infection in health care settings, including nontraditional settings.

2020 will go down in history as the year when the global community was awakened to the fragility of human health and the interdependence of the ecosystem, economy, and humanity. Amid the COVID-19 pandemic, the vulnerability of people with diabetes during a public health emergency became evident by their at least 2 times increased risk of severe disease or death, especially in individuals with poorly controlled diabetes, comorbidities, or both. The disease burden caused by COVID-19, exacerbated by chronic conditions like diabetes, has inflicted a heavy toll on health-care systems and the global economy. | | In this Lancet Commission on diabetes, which embodies 4 years of extensive work on data curation, synthesis, and modelling, we urge policy makers, payers, and planners to collectively change the ecosystem, build capacity, and improve the clinical practice environment. Such actions will enable practitioners to systematically collect data during routine practice and to use these data effectively to diagnose early, stratify risks, define needs, improve care, evaluate solutions, and drive changes at patient, system, and policy levels to prevent and control diabetes and other non-communicable diseases. Emerging evidence regarding the possible damaging effects of severe acute respiratory syndrome coronavirus 2 on pancreatic islets implies the potential worsening of the COVID-19 pandemic and the diabetes epidemic, adding to the urgency of these collective actions. | | Prevention, early detection, prompt diagnosis, and continuing care with regular monitoring and ongoing evaluation are key elements in reducing the growing burden of diabetes. Given the silent and progressive nature of diabetes, it is epidemiological analyses that have provided a framework for identifying populations and subgroups at risk of diabetes and its complications. Although the total prevalence of diabetes reflects disease burden, incidence rates might reflect the effects of interventions among determinant factors that include, but are not limited to, political, socioeconomical, and technological changes within a population, area, or both. | | In 2019, 463 million people had diabetes worldwide, with 80% from low-income and middle-income countries. Over 70% of global deaths are due to non-communicable diseases, including diabetes, cardiovascular disease, cancer, and respiratory disease. On average, diabetes reduces life expectancy in people aged 40–60 years by 4–10 years and independently increases the risk of death from cardiovascular disease, renal disease, and cancer by 1·3–3·0 times. Diabetes is among the leading causes of non-traumatic lower extremity amputation and blindness, especially in people of working age. The co-occurrence of these morbidities severely impairs quality of life, reduces productivity, and causes major suffering.

Crimean-Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5 to 80% (1). CCHF virus (CCHFV, Nairoviridae) exhibits extensive genomic sequence diversity across strains (2, 3). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a GPC variant, present in ticks, have severely impaired function in human cells.

Influenza remains a global health risk and challenge. Currently, NA inhibitors are extensively used to treat influenza, but their efficacy is compromised by the emergence of drug resistant variants. Neutralizing antibodies targeting influenza A virus surface glycoproteins are critical components of influenza therapeutic agents and may provide alternative strategies to the existing countermeasures. However, the major hurdle for the extensive application of antibody therapies lies in the difficulty of generating non-immunogenic antibodies in large quantities rapidly. Here, we report one human monoclonal antibody (mAb), 53C10, isolated from transchromosomic (Tc) cattle exhibits potent neutralization and hemagglutination inhibition titers against different clades of H1N1 subtype influenza A viruses. In vitro selection of antibody escape mutants reveals that 53C10 recognizes a novel non-continuous epitope in the HA head domain involving three amino acid residues, glycine (G), Serine (S) and glutamic acid (E) at positions172, 207 and 212, respectively. The results of our experiments supported a critical role for substitution of arginine at position 207 (S207R) in mediating resistance to 53C10, while substitutions at either G172E or E212A did not alter antibody recognition and neutralization. The E212A mutation may provide structural stability for the epitope, while the substitution G172E probably compensates for loss of fitness introduced by S207R. Our results offer novel insights into the mechanism of action of mAb 53C10 and indicate its potential role in therapeutic treatment of H1 influenza virus infection in humans.IMPORTANCE Respiratory diseases caused by influenza viruses still pose a serious concern to global health and neutralizing antibodies constitute a promising area of antiviral therapeutics. However, the potential application of antibodies is often hampered by the challenge in generating non-immunogenic antibodies in large scale. In the present study, the transchromosomic (Tc) cattle were used for the generation of non-immunogenic monoclonal antibodies (mAbs) and characterization of such mAbs revealed one monoclonal antibody 53C10, exhibiting a potent neutralization activity against H1N1 influenza viruses. Further characterization of the neutralization-escape mutant generated using this mAb, showed that three amino acid substitutions in the HA head domain contributed to the resistance. These findings emphasize the importance of Tc cattle in the production of non-immunogenic mAbs and highlight the potential of 53C10 mAb in the therapeutic application against H1 influenza virus infection in humans.

Risk for severe coronavirus disease 2019 (COVID-19)-associated illness (illness requiring hospitalization, intensive care unit [ICU] admission, mechanical ventilation, or resulting in death) increases with increasing age as well as presence of underlying medical conditions that have shown strong and consistent evidence, including chronic obstructive pulmonary disease, cardiovascular disease, diabetes, chronic kidney disease, and obesity (1-4). Identifying and describing the prevalence of these conditions at the local level can help guide decision-making and efforts to prevent or control severe COVID-19-associated illness. Below state-level estimates, there is a lack of standardized publicly available data on underlying medical conditions that increase the risk for severe COVID-19-associated illness. A small area estimation approach was used to estimate county-level prevalence of selected conditions associated with severe COVID-19 disease among U.S. adults aged ≥18 years (5,6) using self-reported data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) and U.S. Census population data. The median prevalence of any underlying medical condition in residents among 3,142 counties in all 50 states and the District of Columbia (DC) was 47.2% (range = 22.0%-66.2%); counties with the highest prevalence were concentrated in the Southeast and Appalachian region. Whereas the estimated number of persons with any underlying medical condition was higher in population-dense metropolitan areas, overall prevalence was higher in rural nonmetropolitan areas. These data can provide important local-level information about the estimated number and proportion of persons with certain underlying medical conditions to help guide decisions regarding additional resource investment, and mitigation and prevention measures to slow the spread of COVID-19.

Of the eighteen hemagglutinin (HA) subtypes (H1-H18) that have been identified in bats and aquatic birds, many HA subtypes have been structurally characterized. However, several subtypes (H8, H11 and H12) still require characterization. To better understand all of these HA subtypes at the molecular level, HA structures from an A(H4N6) (A/swine/Missouri/A01727926/2015), an A(H8N4) (A/turkey/Ontario/6118/1968), an A(H11N9) (A/duck/Memphis/546/1974), an A(H14N5) A/mallard/Gurjev/263/1982, and an A(H15N9) (A/wedge-tailed shearwater/Western Australia/2576/1979 were determined by X-ray crystallography at 2.2Å, 2.3Å, 2.8Å, 3.0Å and 2.5Å resolution, respectively. The interactions between these viruses and host receptors were studied utilizing glycan-binding analyses with their recombinant HA. The data show that all avian HAs retain their strict binding preference to avian receptors, whereas swine H4 has a weak human receptor binding. The molecular characterization and structural analyses of the HA from these zoonotic influenza viruses not only provide a deeper appreciation and understanding of the structure of all HA subtypes, but also re-iterate why continuous global surveillance is needed.

To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg*bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg*bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg*bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed.

BACKGROUND: Studying the burden and risk factors associated with severe illness from influenza infection in young children in eastern China will contribute to future cost-effectiveness analyses of local influenza vaccine programs. METHODS: We conducted prospective, severe acute respiratory infection (SARI) surveillance at Suzhou University-Affiliated Children's Hospital to estimate influenza-associated hospitalizations in Suzhou University-Affiliated Children's Hospital by month in children younger than 5 years of age from October 2011 to September 2016. SARI was defined as fever (measured axillary temperature >/= 38 degrees C) and cough or sore throat or inflamed/red pharynx in the 7 days preceding hospitalization. We combined SARI surveillance data with healthcare utilization survey data to estimate and characterize the burden of influenza-associated SARI hospitalizations in Suzhou within this age group in the 5-year period. RESULTS: Of the 36,313 SARI cases identified, 2,297 from respiratory wards were systematically sampled; of these, 259 (11%) were influenza positive. Estimated annual influenza-associated SARI hospitalization rates per 1,000 children younger than 5 years of age ranged from 4 (95% confidence interval [CI], 2-5) in the 2012-2013 season to 16 (95% CI, 14-19) in the 2011-2012 season. The predominant viruses were A/H3N2 (59%) in 2011-12, both A/H1N1pdm09 (42%) and B (46%) in 2012-13, A/H3N2 (71%) in 2013-14, A/H3N2 (55%) in 2014-15 and both A/H1N1pdm09 (50%) and B (50%) in 2015-16. The age-specific influenza-associated SARI hospitalization rates for the 5-year period were 11 (95% CI, 8-15) per 1,000 children 0-5 months of age; 8 (95% CI, 7-10) per 1,000 children 6-23 months of age and 5 (95% CI, 4-5) per 1,000 children 24-59 months of age, respectively. CONCLUSIONS: From 2011 to 2016, influenza-associated SARI hospitalization rates in children aged younger than 5 years of age in Suzhou, China, were high, particularly among children 0-5 months of age. Higher hospitalization rates were observed in years where the predominant circulating virus was influenza A/H3N2. Immunization for children > 6 months, and maternal and caregiver immunization for those < 6 months, could reduce influenza-associated hospitalizations in young children in Suzhou.

Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation.

Crimean-Congo hemorrhagic fever virus (CCHFV) infection can result in a severe hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU's immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs.IMPORTANCE Crimean-Congo hemorrhagic fever virus is an important human pathogen with a wide global distribution for which no therapeutic interventions are available. CCHFV encodes a cysteine protease belonging to the ovarian tumor (OTU) family which is involved in host immune suppression. Here we demonstrate that artificially prolonged binding of the OTU to a substrate inhibits virus infection. This provides novel insights into CCHFV OTU function during the viral replicative cycle and highlights the OTU as a potential antiviral target.

We previously demonstrated that despite no airborne transmissibility increase compared to low pathogenic avian influenza viruses, select human isolates of highly pathogenic avian influenza A(H7N9) virus exhibit greater virulence in animal models and a lower threshold pH for fusion. In the current study, we utilized both in vitro and in vivo approaches to identify key residues responsible for hemagglutinin (HA) intracellular cleavage, acid stability, and virulence in mice. We found that the four amino acid insertion (-KRTA-) at the HA cleavage site of A/Taiwan/1/2017 virus is essential for HA intracellular cleavage and contributes to disease in mice. Furthermore, a lysine to glutamic acid mutation at position HA2-64 increased the threshold pH for HA activation, reduced virus stability, and replication in mice. Identification of a key residue responsible for enhanced acid stability of A(H7N9) viruses is of great significance for future surveillance activities and improvements in vaccine stability.

A guanine mononucleotide repeat in the rpsA (tp0279) gene was evaluated for improved strain discrimination using 72 Treponema pallidum-positive specimens. The tandem repeat combined with the enhanced Centers for Disease Control and Prevention typing system resulted in increased discrimination and should be useful for molecular epidemiologic studies on syphilis especially in outbreaks and among men who have sex with men.

Yaws is a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue. The disease primarily affects children under 15 years of age living in low socioeconomic conditions in tropical areas. As a result of a renewed focus on the disease owing to a recent eradication effort initiated by the World Health Organization, we have evaluated a typing method, adapted from and based on the enhanced Centers for Disease Control and Prevention typing method for T. pallidum subsp. pallidum, for possible use in epidemiological studies. Thirty DNA samples from yaws cases in Vanuatu and Ghana, 11 DNA samples extracted from laboratory strains, and 3 published genomic sequences were fully typed by PCR/RFLP analysis of the tpr E, G, and J genes and by determining the number of 60-bp repeats within the arp gene. Subtyping was performed by sequencing a homonucleotide "G" tandem repeat immediately upstream of the rpsA gene and an 84-bp region of tp0548. A total of 22 complete strain types were identified; two strain types in clinical samples from Vanuatu (5q11/ak and 5q12/ak), nine strain types in clinical samples from Ghana (3q12/ah, 4r12/ah, 4q10/j, 4q11/ah, 4q12/ah, 4q12/v, 4q13/ah, 6q10/aj, and 9q10/ai), and twelve strain types in laboratory strains and published genomes (2q11/ae, 3r12/ad, 4q11/ad, 4q12/ad, 4q12/ag, 4q12/v, 5r12/ad, 6r12/x, 6q11/af, 10q9/r, 10q12/r, and 12r12/w). The tpr RFLP patterns and arp repeat sizes were subsequently verified by sequencing analysis of the respective PCR amplicons. This study demonstrates that the typing method for subsp. pallidum can be applied to subsp. pertenue strains and should prove useful for molecular epidemiological studies on yaws.

Recent studies show that Janus Fe3 O4 -TiO2 nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe3 O4 -TiO2 nanoparticles, an in vitro study using a human liver cell line HL-7702 cells was conducted. For comparison, the Janus Fe3 O4 -TiO2 NPs parent material TiO2 NPs was also evaluated. Results showed that both Fe3 O4 -TiO2 NPs and TiO2 NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC-1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO2 NPs induced slightly higher cytotoxicity than Fe3 O4 -TiO2 NPs in HL7702 cells. Western blotting indicated that both TiO2 NPs and Fe3 O4 -TiO2 NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe3 O4 -TiO2 NPs induced higher signal protein expressions than TiO2 NPs under a high treatment dose. However, under a low dose (6.25 mug/cm(2) ), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe3 O4 -TiO2 NPs and TiO2 NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe3 O4 -TiO2 NPs.

Hua Brian L, Bell George W, Kashevsky Helena, Von Stetina Jessica R, Orr-Weaver Terry L. BMC genomics 2018 Aug 19(1) 623

The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that when compared to the 2013 virus HAs, the fifth wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9)HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth wave H7 HAs analyzed in this study.IMPORTANCE The A(H7N9) viruses circulating in China are of great public health concern. Herein, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.

To explore the health effects of multi-heavy metal exposure, Sprague Dawley (SD) rats were orally given one dose of heavy metal mixtures (HMMs). The eight most common detectable heavy metals in Ningbo area are zinc (Zn), copper (Cu), manganese (Mn), chromium (Cr), nickel (Ni), cadmium (Cd), lead (Pb) and mercury (Hg). In this study, mixtures of these eight heavy metals were prepared using the compounds zinc sulfate heptahydrate, cupric sulfate, manganese dichloride, potassium dichromate, nickel dichloride, cadmium dichloride, lead acetate, and methyl mercury chloride with ion mass proportions of 1070.0, 312.6, 173.1, 82.6, 30.0, 13.3, 6.6, and 1.0, respectively. The rats were randomly divided into four groups. Beside the control group, each rat received a corresponding dose of HMMs 215, 464 or 1000 mg per kg body weight (bwt), respectively. The rats were observed for 4 weeks. During the last week of observation, the Morris water maze test was used to investigate spatial learning and memory in the treated rats. The rats were exsanguinated under complete chloral hydrate anesthesia and organ coefficients were measured. Biochemical tests of blood and serum samples were carried out. The results showed abnormalities in the hematological system, decreased renal function, hepatic injury and disturbances in the electrolyte balance of the rats treated with a high dose of HMMs. Death of some rats was also observed. This paper analyzed how a one-time high dose oral administration of HMMs induced systemic toxicity. © 2018 The Royal Society of Chemistry.

Background: A single subtype of canine influenza virus (CIV), A(H3N8), was circulating in the United States until a new subtype, A(H3N2), was detected in Illinois in spring 2015. Since then, this CIV has caused thousands of infections in dogs in multiple states. Methods: In this study, genetic and antigenic properties of the new CIV were evaluated. In addition, structural and glycan array binding features of the recombinant hemagglutinin were determined. Replication kinetics in human airway cells and pathogenesis and transmissibility in animal models were also assessed. Results: A(H3N2) CIVs maintained molecular and antigenic features related to low pathogenicity avian influenza A(H3N2) viruses and were distinct from A(H3N8) CIVs. The structural and glycan array binding profile confirmed these findings and revealed avian-like receptor-binding specificity. While replication kinetics in human airway epithelial cells was on par with that of seasonal influenza viruses, mild-to-moderate disease was observed in infected mice and ferrets, and the virus was inefficiently transmitted among cohoused ferrets. Conclusions: Further adaptation is needed for A(H3N2) CIVs to present a likely threat to humans. However, the potential for coinfection of dogs and possible reassortment of human and other animal influenza A viruses presents an ongoing risk to public health.

Background: Neuraminidase (NA) inhibitors are the recommended antiviral medications for influenza treatment. However, their therapeutic efficacy can be compromised by NA changes that emerge naturally and/or following antiviral treatment. Knowledge of which molecular changes confer drug resistance of influenza A(H7N9) viruses (group 2NA) remains sparse. Methods: Fourteen amino acid substitutions were introduced into the NA of A/Shanghai/2/2013(H7N9). Recombinant N9 (recN9) proteins were expressed in a baculovirus system in insect cells and tested using the Centers for Disease Control and Prevention standardized NA inhibition (NI) assay with oseltamivir, zanamivir, peramivir, and laninamivir. The wild-type N9 crystal structure was determined in complex with oseltamivir, zanamivir, or sialic acid, and structural analysis was performed. Results: All substitutions conferred either reduced or highly reduced inhibition by at least 1 NA inhibitor; half of them caused reduced inhibition or highly reduced inhibition by all NA inhibitors. R292K conferred the highest increase in oseltamivir half-maximal inhibitory concentration (IC50), and E119D conferred the highest zanamivir IC50. Unlike N2 (another group 2NA), H274Y conferred highly reduced inhibition by oseltamivir. Additionally, R152K, a naturally occurring variation at the NA catalytic residue of A(H7N9) viruses, conferred reduced inhibition by laninamivir. Conclusions: The recNA method is a valuable tool for assessing the effect of NA changes on drug susceptibility of emerging influenza viruses.

Antiviral drug resistance HBV variants (HBV-DR) occur spontaneously in chronic hepatitis B (CHB) patients and after exposure to nucleos(t)ide analogues (NUCs). We determined the prevalence of HBV-DR variants among participants of the Hepatitis B Research Network (HBRN) Cohort Study conducted at 21 sites in the United States (US) and Canada. Samples obtained from 1342 CHB participants aged ≥18 years, and who were currently not receiving NUCs, were tested for HBV-DR variants by Sanger sequencing. In addition, next generation sequencing (NGS) was used to characterize HBV-DR variants from 66 participants with and 66 participants with no prior NUC exposure matched for HBV genotype and HBV DNA level. Half the participants were men, 75% Asian, 26% HBeAg-positive. Primary HBV-DR variants were detected by Sanger sequencing in 16 (1.2%) participants: 2/142 (1.4%) with and 14/1200 (1.2%) without prior NUC exposure; only 1 of these 16 had a secondary variant. In total, 23 (1.7%) participants had secondary variants, including 1 with prior NUC experience. In the subset of 132 participants, NGS detected HBV-DR variants in a higher proportion of participants: primary variants in 18 (13.6%) [8 (12.1%) with, and 10 (15.2%) without prior NUC therapy], and secondary variants in 10 (7.6%) participants. Based on Sanger sequencing, prevalence of primary HBV-DR variants is low (1.2%) among adults with CHB in US/Canada. The similar low prevalence of HBV-DR variants in participants with and without NUC treatment suggests transmission of these variants is uncommon.

BACKGROUND: Human noroviruses are a major cause of viral gastroenteritis and are the main etiological agents of acute gastroenteritis outbreaks. An increasing number of outbreaks and sporadic cases of norovirus have been reported in China in recent years. There was a large acute gastroenteritis outbreak at a university in Henan Province, China in the past five years. We want to identify the source, transmission routes of the outbreak by epidemiological investigation and laboratory testing in order to provide the effective control measures. METHODS: The clinical cases were investigated, and analysed by descriptive epidemiological methods according to factors such as time, department, grade and so on. Samples were collected from clinical cases, healthy persons, the environment, water, and food at the university. These samples were tested for potential bacteria and viruses. The samples that tested positive for norovirus were selected for whole genome sequencing and the sequences were then analysed. RESULTS: From 4 March to 3 April 2015, a total of 753 acute diarrhoea cases were reported at the university; the attack rate was 3.29%. The epidemic curve showed two peaks, with the main peak occurring between 10 and 20 March, accounting for 85.26% of reported cases. The rates of norovirus detection in samples from confirmed cases, people without symptoms, and environmental samples were 32.72%, 17.39%, and 9.17%, respectively. The phylogenetic analysis showed that the norovirus belonged to the genotype GII.17. CONCLUSIONS: This is the largest and most severe outbreak caused by genotype GII.17 norovirus in recent years in China. The GII.17 viruses displayed high epidemic activity and have become a dominant strain in China since the winter of 2014, having replaced the previously dominant GII.4 Sydney 2012 strain.

Whole genome sequences of representative highly pathogenic avian influenza A(H5) viruses from Vietnam were generated, comprising samples from poultry outbreaks and active market surveillance collected from January 2012 to August 2015. Six hemagglutinin gene clades were characterized. Clade 1.1.2 was predominant in southern Mekong provinces throughout 2012 and 2013, but gradually disappeared and was not detected after April 2014. Clade 2.3.2.1c viruses spread rapidly during 2012 and were detected in the south and center of the country. A number of clade 1.1.2 and 2.3.2.1c inter-clade reassortant viruses were detected with different combinations of internal genes derived from 2.3.2.1a and 2.3.2.1b viruses indicating extensive co-circulation. Although reassortment generated genetic diversity at the genotype level, there was relatively little genetic drift within the individual gene segments suggesting genetic stasis over recent years. Antigenically, clade 1.1.2, 2.3.2.1a, 2.3.2.1b, 2.3.2.1c viruses remained related to earlier viruses and WHO recommended pre-pandemic vaccine strains representing these clades. Clade 7.2 viruses, although only detected in small numbers, were the exception as indicated by introduction of a genetically and antigenically diverse strain in 2013. Clade 2.3.4.4 viruses (H5N1 and H5N6) were likely introduced in April 2014 and appeared to gain dominance across northern and central regions. Antigenic analyses of clade 2.3.4.4 viruses compared to existing clade 2.3.4 candidate vaccine viruses (CVV) indicated the need for an updated vaccine virus. A/Sichuan/26221/2014 (H5N6), was developed and ferret antisera generated against this virus was demonstrated to inhibit some but not all clade 2.3.4.4 viruses suggesting consideration of alternative clade 2.3.4.4 CVVs. IMPORTANCE: Highly pathogenic avian influenza (HPAI) A(H5) viruses have circulated continuously in Vietnam since 2003 resulting in hundreds of poultry outbreaks and sporadic human infections. Despite significant reduction in the number of human infections in recent years, poultry outbreaks continue to occur and the virus continues to diversify. Vaccination of poultry has been used as a means to control spread and impact of the virus but due to the diversity and changing distribution of antigenically distinct viruses, the utility of vaccines in the face of mismatched circulating strains remains questionable. This study assesses the putative amino acid changes in viruses leading to antigenic variability, underscoring the complexity of vaccine selection for both veterinary and public health purposes. Given the overlapping geographic distribution of multiple, antigenically distinct clades of HPAI A(H5) viruses in Vietnam, the vaccine efficacy of bivalent poultry vaccine formulations should be tested in the future.

Nontuberculous mycobacteria (NTM) are a rare cause of ventriculoperitoneal shunt infections. We describe the isolation and identification of a novel, rapidly growing, nonpigmented NTM from an abdominal cerebrospinal fluid pseudocyst. The patient presented with fevers, nausea, and abdominal pain and clinically improved after shunt removal. NTM identification was performed by amplicon and whole-genome sequencing.