Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in All of Us Research Program Participants, 2 January to 18 March 2020.

BACKGROUND: With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs). RESULTS: The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.

Pertussis vaccines.

PURPOSE OF REVIEW: Pertussis is a vaccine preventable cough illness. It can be controlled by universal pertussis vaccination. RECENT FINDINGS: Pertussis cases and deaths in children are at a record low number. More complete use of adolescent/adult vaccine can further reduce morbidity and mortality. SUMMARY: Considerable progress in the control of pertussis has occurred over the last 75 years. The universal use of Tdap vaccines in all pregnant women will prevent virtually all pertussis deaths.

ZIKA Virus Neutralizing Antibody Kinetics in Antenatally Exposed Infants.

BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

Highlights of the 12th International Bordetella Symposium.

To commemorate the 100th anniversary of the Nobel prize being awarded to Jules Bordet, the discoverer of Bordetella pertussis, the 12th International Bordetella Symposium was held from 9 to 12 April 2019 at the Université Libre de Bruxelles, where Jules Bordet studied and was Professor of Microbiology. The symposium attracted more than 300 Bordetella experts from 34 countries. They discussed the latest epidemiologic data and clinical aspects of pertussis, Bordetella biology and pathogenesis, immunology and vaccine development, and genomics and evolution. Advanced technological and methodological tools provided novel insights into the genomic diversity of Bordetella and a better understanding of pertussis disease and vaccine performance. New molecular approaches revealed previously unrecognized complexity of virulence gene regulation. Innovative insights into the immune responses to infection by Bordetella resulted in the development of new vaccine candidates. Such discoveries will aid in the design of more effective approaches to control pertussis and other Bordetella-related diseases.

Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants.

BACKGROUND: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes. METHODS: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed. RESULTS: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life. CONCLUSIONS: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.

Zika Virus Infection in Pregnant Women in Rio de Janeiro.

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

Clinical Characteristics of Measles in Previously Vaccinated and Unvaccinated Patients in California.

Background: Measles vaccine failure was first described in 1972. Over the next 20 years, vaccine failure was extensively studied, but during the last 25 years few investigations have been performed. We describe the clinical characteristics of measles in previously vaccinated and unvaccinated patients in California. Methods: All confirmed measles cases reported to the California Department of Public Health from 1 January 2000 through 31 December 2015 were reviewed. Clinical characteristics (rates of hospitalization, cough, coryza, conjunctivitis, and fever) were compared between the previously unvaccinated, those who had had 1 dose of vaccine, and those who had had ≥2 doses of measles vaccine. Results: There were 232 confirmed measles cases in whom vaccination status was verified; 80% were unvaccinated, 9% had had 1 dose of measles vaccine, and 11% had had ≥2 doses of measles vaccine. Subjects who had had ≥2 doses of measles vaccine had lower rates of hospitalization, cough, coryza, conjunctivitis, and fever than subjects who had 1 dose of measles vaccine or who were unimmunized. Conclusions: Vaccine failure measles cases were less ill than cases that occurred in unvaccinated patients. Nevertheless, these cases still required the same amount of public health effort in tracing contacts as in cases who were unvaccinated.

Effect of Ovarian Hormones and Mating Experience on the Preference of Female Mice to Investigate Male Urinary Pheromones.

In female mice, the expression of receptive lordosis behavior requires estradiol and progesterone actions in the nervous system; however, the contribution of these hormones to females' motivation to seek out male pheromones is less clear. In an initial experiment, sexually naïve ovary-intact female mice preferred to investigate (make nasal contact with) testes-intact male as opposed to estrous female urine, provided they were in vaginal estrus. In a second experiment, groups of sexually naïve and mating-experienced, ovariectomized females were tested for urinary pheromone preference first without and then with ovarian hormone replacement. Without hormone replacement, sexually naïve ovariectomized females showed no preference for male over female urinary pheromones whereas mating-experienced females preferred to investigate male pheromones. Ovariectomized females in both groups preferred male over female urine after sequential s.c. injections with estradiol benzoate followed 2 days later with progesterone and after prolonged (7 days) exposure to estradiol alone. Our results indicate that in sexually naïve female mice estradiol, perhaps aided by progesterone, is required to motivate a preference to seek out male pheromones whereas after mating experience females' preference to investigate male pheromones persists even in the absence of ovarian hormone action.

Effectiveness of Prenatal Tetanus, Diphtheria, and Acellular Pertussis Vaccination on Pertussis Severity in Infants.

BACKGROUND: All US women are recommended to receive a tetanus, diphtheria, and acellular pertussis (Tdap) vaccine at 27-36 weeks gestation during each pregnancy to reduce the risk of pertussis to their infants. The impact of this strategy on severity of disease among infected infants has not been evaluated. METHODS: We use a retrospective cohort study design evaluating whether pertussis-infected infants born in 2011-2015 whose mothers received Tdap vaccine during pregnancy had less severe pertussis, resulting in a lower risk of hospitalization or intensive care unit admission compared with infants born to unvaccinated mothers. RESULTS: Infected infants of vaccinated mothers were significantly less likely to be hospitalized and had significantly shorter hospital stays compared with infants born to unvaccinated mothers, after adjustment for chronological and gestational age and receipt of diphtheria and tetanus toxoids and acellular pertussis vaccine. Unadjusted and adjusted vaccine effectiveness for preventing hospitalization among infants with pertussis was 72% (95% confidence interval [CI], 49%-85%) and 58% (95% CI 15%-80%), respectively. No infants born to vaccinated mothers required intubation or died of pertussis. CONCLUSIONS: Infants with pertussis whose mothers received Tdap during pregnancy had a significantly lower risk of hospitalization and intensive care unit admission and shorter hospital stays. Prenatal Tdap vaccination is a critical strategy for reducing the morbidity and mortality from pertussis.

Subacute Sclerosing Panencephalitis: The Devastating Measles Complication That Might Be More Common Than Previously Estimated.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles. We reviewed California cases from 1998-2015 to understand risk factors for SPPE and estimate incidence. METHODS: SSPE cases had clinically compatible symptoms and measles antibody detection in cerebrospinal fluid (CSF) or medical record documentation of SSPE. Cases were identified though a state death certificate search, Centers for Disease Control and Prevention reports, or investigations for undiagnosed neurologic disease. Measles detection in CSF was performed by serology at the California Department of Public Health or at clinical laboratories. RESULTS: Seventeen SSPE cases were identified. Males outnumbered females 2.4:1. Twelve (71%) cases had a history of measles-like illness; all 12 had illness prior to 15 months of age. Eight (67%) children were exposed to measles in California. SSPE was diagnosed at a median age of 12 years (3-35 years), with a latency period of 9.5 years (2.5-34 years). Among measles cases reported to CDPH during 1988-1991, the incidence of SSPE was 1:1367 for children <5 years, and 1:609 for children <12 months at time of measles disease. CONCLUSIONS: SSPE cases in California occurred at a high rate among unvaccinated children, particularly those infected during infancy. Protection of unvaccinated infants requires avoidance of travel to endemic areas, or early vaccination prior to travel at age 6-11 months. Clinicians should be aware of SSPE in patients with compatible symptoms, even in older patients with no specific history of measles infection. SSPE demonstrates the high human cost of "natural" measles immunity.

Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and Their Relationship to Birth Outcomes.

BACKGROUND: Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes. METHODS: A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. RESULTS: 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397). CONCLUSIONS: Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies.

DREADD-induced silencing of the medial amygdala reduces the preference for male pheromones and the expression of lordosis in estrous female mice.

Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing. Sexually naïve females received bilateral Me injections of an adeno-associated virus carrying an inhibitory DREADD. Females were later ovariectomized, treated with ovarian hormones, and given behavioral tests following intraperitoneal injections of saline or clozapine-N-oxide (CNO; which hyperpolarizes infected Me neurons). CNO attenuated females' preference to investigate male vs. female urinary odors. Repeated CNO treatment also slowed the increase in lordosis otherwise seen in females given saline. However, when saline was given to females previously treated with CNO, their lordosis quotients were as high as other females repeatedly given saline. No disruptive behavioral effects of CNO were seen in estrous females lacking DREADD infections of the Me. Finally, CNO attenuated the ability of male pheromones to stimulate Fos expression in the Me of DREADD-infected mice but not in non-infected females. Our results affirm the importance of Me signaling in females' chemosensory preferences and in the acute expression of lordosis. However, they provide no indication that Me signaling is required for the increase in receptivity normally seen after repeated hormone priming and testing with a male.

A comparison of the effects of male pheromone priming and optogenetic inhibition of accessory olfactory bulb forebrain inputs on the sexual behavior of estrous female mice.

Previous research has shown that repeated testing with a stimulus male is required for ovariectomized, hormone-primed female mice to become sexually receptive (show maximal lordosis quotients; LQs) and that drug-induced, epigenetic enhancement of estradiol receptor function accelerated the improvement in LQs otherwise shown by estrous females with repeated testing. We asked whether pre-exposure to male pheromones ('pheromone priming') would also accelerate the improvement in LQs with repeated tests and whether optogenetic inhibition of accessory olfactory bulb (AOB) projection neurons could inhibit lordosis in sexually experienced estrous female mice. In Experiment 1, repeated priming with soiled male bedding failed to accelerate the progressive improvement in LQs shown by estrous female mice across 5 tests, although the duration of each lordosis response and females' investigation of male body parts during the first test was augmented by such priming. In Experiment 2, acute optogenetic inhibition of AOB inputs to the forebrain during freely moving behavioral tests significantly reduced LQs, suggesting that continued AOB signaling to the forebrain during mating is required for maximal lordotic responsiveness even in sexually experienced females. Our results also suggest that pheromonal stimulation, by itself, cannot substitute for the full complement of sensory stimulation received by estrous females from mounting males that normally leads to the progressive improvement in their LQs with repeated testing.

Pertussis in Young Infants Throughout the World.

In typical pertussis in young infants, the child will appear deceptively well; he or she will have coryza, sneezing, and a mild cough. There is no fever. This progresses to gagging, gasping, eye bulging, bradycardia, cyanosis, and vomiting. There is leukocytosis with lymphocytosis and apneic episodes. Deaths relate to leukocytosis, pulmonary hypertension, and pneumonia. The source of pertussis in young infants is most often a family member with cough illness that is not recognized as pertussis. Diagnosis is based on culture/polymerase chain reaction and leukocytosis with lymphocytosis. Treatment depends on macrolide antibiotic therapy and intubation, with assisted ventilation and oxygen. Prevention is based on prophylactic macrolide treatment, immunization starting at 6 weeks of age, and immunization of all pregnant women in the second or third trimester.

Risk Factors Associated With Infant Deaths From Pertussis: A Case-Control Study.

BACKGROUND: In the current era, most pertussis deaths occur in infants <3 months of age. Leukocytosis with lymphocytosis and pneumonia are commonly observed among cases of severe pertussis. METHODS: Risk factors associated with fatal pertussis were identified by comparing fatal pertussis cases among patients <120 days of age occurring from 1 January 1998 through 26 December 2014, matched by age (<120 days), county of residence, and closest symptom onset date with 1-4 nonfatal hospitalized cases. California Department of Public Health surveillance data were reviewed to identify cases; demographics, clinical presentation, and course were abstracted from corresponding birth and medical records. Logistic regression and classification tree analyses were used to examine the risk of fatal pertussis with respect to identified factors. RESULTS: Fifty-three fatal infant pertussis cases were identified and compared with 183 nonfatal hospitalized pertussis cases. Fatal cases had significantly lower birth weight, younger gestational age, younger age at time of cough onset, and higher peak white blood cell (WBC) and lymphocyte counts. Fatal cases were less likely to have received macrolide antibiotics and more likely to have received steroids or nitric oxide and to develop pulmonary hypertension, seizures, encephalitis, and pneumonia. Additionally, exchange transfusion, extracorporeal membrane oxygenation, and intubation occurred significantly more frequently among fatal cases. In multivariate analyses, peak WBC count, birth weight, intubation, and receipt of nitric oxide were predictors of death. CONCLUSIONS: Early recognition of pertussis in young infants and treatment with appropriate antibiotic therapy are important in preventing death. Several risk factors are strongly associated with fatal pertussis in infants.

Serological misdiagnosis of acute liver failure associated with echovirus 25 due to immunological similarities to hepatitis A virus and prozone effect.

We describe a case of acute liver failure caused by echovirus 25 (E25) in a previously healthy 2-year-old boy. Initial serological studies were consistent with hepatitis A virus (HAV), with prozone phenomenon. The similarity of E25 to HAV may obscure accurate diagnosis in some cases of hepatitis.

Processing by the main olfactory system of chemosignals that facilitate mammalian reproduction.

This article is part of a Special Issue "Chemosignals and Reproduction". Most mammalian species possess two parallel circuits that process olfactory information. One of these circuits, the accessory system, originates with sensory neurons in the vomeronasal organ (VNO). This system has long been known to detect non-volatile pheromonal odorants from conspecifics that influence numerous aspects of social communication, including sexual attraction and mating as well as the release of luteinizing hormone from the pituitary gland. A second circuit, the main olfactory system, originates with sensory neurons in the main olfactory epithelium (MOE). This system detects a wide range of non-pheromonal odors relevant to survival (e.g., food and predator odors). Over the past decade evidence has accrued showing that the main olfactory system also detects a range of volatile odorants that function as pheromones to facilitate mate recognition and activate the hypothalamic-pituitary-gonadal neuroendocrine axis. We review early studies as well as the new literature supporting the view that the main olfactory system processes a variety of different pheromonal cues that facilitate mammalian reproduction.

Ongoing Measles in the Developed and Developing World.

Measles is a vaccine-preventable illness. Nevertheless, in recent years, measles is still endemic and epidemic in both the developed world and the developing world. The public perception of measles in the past was that it was not a big deal. However, measles is associated with a number of complications which can be places in three categories which are: acute(diarrhea, otitis media, pneumonia, encephalitis, seizures, and death) and delayed-subacute sclerosing panencephalitis (SSPE) and post-measles immune amnesia. Contrary to the beliefs of the anti-vaccine lobby, measles is bad. In acute measles, the death rate is 1-3 per 1000 and the risk of encephalitis is 1 per 1000. Relatively recent investigations indicate that SSPE is considerably more common than previously believed. The worldwide contribution of post-measles immune amnesia to morbidity and mortality is likely to be huge. In exposure situations, two doses of measles vaccine will prevent 99% of cases. Presently in the United States, the first dose is given at 12 through 15 months of age. The second dose is most often administered at 4 through 6 years of age. In my opinion, the second dose of measles vaccine should be given 4-6 weeks after the first dose rather than at 4-6 years of age. Children who don't have antibody to measles should not travel to risk areas.

The role of upregulated miRNAs and the identification of novel mRNA targets in prostatospheres.

TICs are characterized by their ability to self-renew, differentiate and initiate tumor formation. miRNAs are small noncoding RNAs that bind to mRNAs resulting in regulation of gene expression and biological functions. The role of miRNAs and TICs in cancer progression led us to hypothesize that miRNAs may regulate genes involved in TIC maintenance. Using whole genome miRNA and mRNA expression profiling of TICs from primary prostate cancer cells, we identified a set of up-regulated miRNAs and a set of genes down-regulated in PSs. Inhibition of these miRNAs results in a decrease of prostatosphere formation and an increase in target gene expression. This study uses genome-wide miRNA profiling to analyze expression in TICs. We connect aberrant miRNA expression and deregulated gene expression in TICs. These findings can contribute to a better understanding of the molecular mechanisms governing TIC development/maintenance and the role that miRNAs have in the fundamental biology of TICs.