Fatal Virus Infection Research Articles

Distribution and genetic diversity of Bombyx mori nucleopolyhedrovirus in mass-reared silkworms in Thailand

Silk is an economically and culturally important product of Thailand that is threatened by the outbreaks of the Bombyx mori nucleopolyhedrovirus (BmNPV) in silkworm rearings. BmNPV infects the larval stages of the silkworm Bombyx mori, causing fatal viral infection and preventing the larvae from reaching the pupal stage. Numerous BmNPV isolates have been described from silk producing countries from all over the world. In this study, the geographic distribution of BmNPV in Thailand was analyzed by collecting 18 samples from different regions. The BmNPV samples were analyzed by PCR and whole genome sequencing was performed for eight specimens. Their genome size ranged from 125,888 bp to 126,783 bp, comprising 138 open reading frames. Although the sequenced BmNPV genomes could be phylogenetically differentiated, a correlation between geographic and genetic distance was not observed indicating a close relationship between the BmNPV from Thailand.

A study on evaluation and correlation of serological methods and platelet count for diagnosis of dengue virus infection.

Dengue is arthropod-borne, acute potentially fatal viral infection, endemic in many tropical and sub-tropical countries having public health threat globally in recent era. Effective and prompt diagnosis is very essential to reduce morbidity and mortality associated with severe form. Diagnosis by dengue-specific markers like Non-Structural protein 1 antigen or IgM/IgG antibody by serological method is the choice of investigation and the most widely used non-specific biomarker is platelet count. To evaluate and correlate results of two serological diagnostic methods (Dengue NS1 Antigen and Dengue IgM antibodies by Enzyme-Linked Immunosorbent Assay) and with platelet count for diagnosis of Dengue infection. Retrospective cross-sectional study for duration of 6 months from April 2022 to September 2022. Total 4063 serum samples of dengue suspected patients were tested according to duration of illness by ELISA for presence of NS1 Ag (≤5 days of illness) or IgM antibody (>5 days of illness). 393/4063 were detected positive by either method (NS1/IgM) and majority of patients were diagnosed between 3-8 days of illness. 248/2250 were tested positive for dengue NS1-Ag only, while 145/1813 were seropositive by dengue IgM only. Thrombocytopenia (platelet counts <100000/mm3) found in 301/393 seropositive cases which was also observed in NS1 (207/248 cases) and IgM (94/145 cases) seropositive patients. Dengue specific parameters (NS1/IgM detection) in combination with platelet count helps in accurate, timely diagnosis and better monitoring in clinical management of patients.

Seroprevalence and risk factors of sheep and goat pox virus in selected districts of Wolaita Zone, Southern Ethiopia.

Sheep and goat pox (SGP) virus infection is a highly fatal viral infection of small ruminants that causes major production losses in sheep and goats in Ethiopia while also limiting international trade. This study aimed to estimate the seroprevalence of SGP infection and assess related risk variables. A cross-sectional study was conducted from February to August 2023 on 384 serum samples taken from sheep and goats. A serum neutralization test was conducted to detect the presence of antibodies against the SGP virus in Wolaita Sodo Regional Laboratory. The overall seroprevalence rate of SGP was 4.95%. Factors such as sheep (8.26%), female sheep and goats (7.45%), older sheep and goats (8.33%), larger flock size of sheep and goats (10.47%), poorly conditioned sheep and goats (31.58%), sheep and goats with a tick on their skin (10.38%), and animals that had not been vaccinated (5.17%) were found to have higher seroprevalence. Furthermore, the seropositivity in sheep was five times greater than in goats (adjusted odds ratio [AOR], 4.73; 95% confidence interval [CI], 1.39-15.99). Additionally, large-sized flocks of sheep and goats were more likely to be seropositive to pox disease than small-sized flocks (AOR, 6.73; 95% CI, 1.58-28.67). Thus, the study revealed the prevalence of SGP in the Wolaita zone. Additional research should be conducted to estimate the extent of the disease at the regional level, and management measures should be implemented to reduce the economic losses associated with this condition.

Reversible Cytotoxic Edema in Patients with COVID-19 Associated Encephalitis Presenting Status Epilepticus

Coronavirus disease 2019 (COVID-19) is a serious infectious disease with multisystem alteration including neurological complications. COVID-19 associated encephalitis is a potentially fatal viral infection of the brain. Diffusion-weighted images (DWI) are a useful evaluation modality of cytotoxic edema in patients with encephalitis. We report on the reversible DWI change in a patient with COVID-19 associated encephalitis, who had diffused cytotoxic edema in the affected temporal lobe and accompanied status epilepticus. Sequential imaging showed that the cytotoxic edema in DWI confirmed recovery to normal after 12 days in the presence of cortical edema in fluid-attenuated inversion recovery image after aggressive neurocritical management. Thus, prompt, proper management is indispensable during the acute period and DWI may be a valuable tool for reflecting the clinical course of COVID-19 associated encephalitis.

How does COVID-19 vaccination affect long-COVID symptoms?

The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition. This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate. In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032). In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.

Radical thermal therapy against infection with decapod iridescent virus 1 (DIV1)

Decapod iridescent virus 1 (DIV1) is a newly found double-stranded DNA virus that can cause huge losses to the aquaculture industry. The potential of thermal therapy to treat and cure the disease, namely infection with DIV1 (iDIV1), in white leg shrimp Penaeus vannamei, was evaluated in this study with the thermal treatment and temperature restoration (TT/TR) protocol. After being challenged with DIV1 strain SHIV20141215 via intramuscular injection, the shrimp in different groups received a 15-day TT from 28 °C to 38 °C, respectively, and then 15-day TR at 28 °C. All shrimp in groups with TT below 32 °C died rapidly within 5 d post-infection (dpi) with confirmatory iDIV1 by TaqMan qPCR, histopathological H&E staining and ISDL, and cytopathological TEM. The development of iDIV1 was suppressed at 34 °C but revived after TT to 28 °C. Elimination of DIV1 at 36 °C was confirmed with the same survival curve of the unchallenged control group, no replication of DIV1 DNA copies, and negative results of clinical signs, histopathology, ISDL, and TEM during the TT/TR process. The reproducibility validation of TT/TR at 36 °C verified the elimination of DIV1 from the challenged shrimp. This is the first report of radical thermal therapy from the emerging disease iDIV1 using TT at 36 °C, which provides an innovative measure to cure the fatal viral infection, especially for the larvae and broodstock of shrimp varieties with special genetic properties.

Linezolid as Potent Inhibitor of SARS-CoV-2 Nsp13 Helicase: Grid Based Docking Approach

Abstract: A diversified originator in humans and wildlife, the corona virus (COVID-19) is an enveloped RNA virus. Six different species have been shown to be the root of human sickness. Human diseases are greatly influenced by viral infections, and one of the most recent global epidemics is the appearance of the new corona. The SARS (Severe Acute Respiratory Syndrome) virus, a potentially fatal viral infection, was caused by the SS-RNA virus from the enveloped corona virus family. In many nations around the world, disease is rapidly expanding. 462,684 confirmed cases and 20,834 fatalities had been reported as of March 26, 2020, internationally. On March 11, 2020, COVID-19 was declared a pandemic by the World Health Organization (WHO). There are numerous medication trials ongoing, and some of the outcomes are encouraging. However, since there is no vaccine, the only approach to fight the virus is through preventative measures. Patients with bacterial nosocomial pneumonia were successfully treated with the antibiotic "Linezolid" by receiving an intravenous dose of 600 mg of linezolid every 12 hours for 7 to 10 days. All of the patients made a full recovery and were allowed to leave the hospital. Additionally, previous studies have shown that linezolid is more clinically and microbiologically effective than other antibiotics (vancomycin). The goal of the current study was to use a molecular docking approach to evaluate linezolid's potential against SAR-CoV-2 infection.

Linezolid as Potent Inhibitor of SARS-CoV-2 Nsp13 Helicase: Grid Based Docking Approach

A diversified originator in humans and wildlife, the corona virus (COVID-19) is an enveloped RNA virus. Six different species have been shown to be the root of human sickness. Human diseases are greatly influenced by viral infections, and one of the most recent global epidemics is the appearance of the new corona. The SARS (Severe Acute Respiratory Syndrome) virus, a potentially fatal viral infection, was caused by the SS-RNA virus from the enveloped corona virus family. In many nations around the world, disease is rapidly expanding. 462,684 confirmed cases and 20,834 fatalities had been reported as of March 26, 2020, internationally. On March 11, 2020, COVID-19 was declared a pandemic by the World Health Organization (WHO). There are numerous medication trials ongoing, and some of the outcomes are encouraging. However, since there is no vaccine, the only approach to fight the virus is through preventative measures. Patients with bacterial nosocomial pneumonia were successfully treated with the antibiotic "Linezolid" by receiving an intravenous dose of 600 mg of linezolid every 12 hours for 7 to 10 days. All of the patients made a full recovery and were allowed to leave the hospital. Additionally, previous studies have shown that linezolid is more clinically and microbiologically effective than other antibiotics (vancomycin). The goal of the current study was to use a molecular docking approach to evaluate linezolid's potential against SAR-CoV-2 infection.

Clinical spectrum and management of dystonia in patients with Japanese encephalitis: A systematic review.

BackgroundJapanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD) including dystonia. Dystonic features in JE are uncommon. Here, we have tried to summarize the clinical features and management of dystonia among JE patients with a comprehensive literature search.MethodsVarious databases, including PubMed, Embase, and Google Scholar, were searched against the predefined criteria using suitable keywords combination and boolean operations. Relevant information from observational and case studies was extracted according to the author, dystonic features, radiological changes in the brain scans, treatment options, and outcome wherever provided.ResultWe identified 19 studies with a total of 1547 JE patients, the diagnosis of which was confirmed by IgM detection in serum and/or cerebrospinal fluid in the majority of the patients (88.62%). 234 (15.13%) of JE patients had dystonia with several types of focal dystonia being present in 131 (55.98%) either alone or in combination. Neuroimaging showed predominant involvement of thalami, basal ganglia, and brainstem. Oral medications including anticholinergics, GABA agonists, and benzodiazepines followed by botulinum toxin were the most common treatment modalities.ConclusionDystonia can be a disabling consequence of JE, and various available medical therapies can significantly improve the quality of life. Owing to insufficient studies on the assessment of dystonia associated with JE, longitudinal studies with a larger number of patients are warranted to further clarify the clinical course, treatment, and outcome of dystonia.

Crimean-Congo haemorrhagic fever-induced liver injury: A systematic review and meta-analysis.

Crimean-Congo haemorrhagic fever (CCHF) is a fatal acute tick-borne viral infection and substantial emerging global public health threat. This illness has a high case fatality rate of up to 40%. The liver is one of the important target organs of the CCHF virus. The aim of this meta-analysis to evaluate the correlation between CCHF and liver injury and draw more generalised inferences about the abnormal serum markers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) in CCHF patients. A literature search was accomplished for published eligible articles with MEDLINE/PubMed and Embase databases. All eligible observational studies and case series were included from around the world. The inclusion criteria were articles describing liver injury biomarkers amongst patients diagnosed with CCHF. Data from 18 studies, consisting of 1238 patients with CCHF were included in this meta-analysis. Overall pooled incidence of at least one raised liver injury biomarker was 77.95% (95% CI, I2 = 88.50%, P<.0001). Similarly, pooled incidence of elevated AST and ALT was 85.92% (95% CI, I2 =85.27%, P<.0001) and 64.30% (95% CI, I2 = 88.32%, P<.0001), respectively. Both Egger and Begg-Mazumdar's tests detected no apparent publication bias in all three meta-analyses (P>.05). Our study shows that CCHF has a very detrimental effect on liver function. Abnormal liver function may lead to poor prognosis and increased morbidity and mortality in CCHF patients. Hence, Physicians must recognise and continuously monitor these biomarkers, since these markers may aid in early stratification of prognosis and the prevention of severe outcomes in infection with such a high case fatality rate.

Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney Disease.

Through the discovery of direct-acting antiviral therapies over the last decade, hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease, is a risk factor for progression of CKD, is associated with higher morbidity and mortality in patients receiving dialysis, and leads to worse allograft and patient outcomes in recipients of kidney transplants. Clinical trial and real-world data of direct-acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease, including patients with CKD, ESKD, and those who have received a kidney transplant.

Serosurveillance of rabies antibodies in dogs in Mumbai region by using indirect ELISA

Rabies is a highly fatal viral infection of the central nervous system affecting all warm-blooded animals including humans. To implement the preventive and control measures, it is important to decide the status of anti-rabies antibodies in dogs. Out of 120 serum samples, 47 (39.2 %) serum samples, showed an antibody titre equal to or above the cut off value of 0.5 IU/ml. The maximum number of dogs showed anti-rabies antibody titres equal to or above the cut-off value of 0.5 IU/ml after <1 month pre-exposure to the rabies vaccine. In 15 serum samples of pet dogs, we observed 13 (86.66 %) dogs with protective anti-rabies antibody titre. Statistical analysis suggests that the age of the animal had no significant effect on anti-rabies antibody titre in vaccinated pet dogs. The overall low seroprevalence of anti-rabies antibody in stray dogs indicates their susceptibility to rabies infection and thus posing a risk of rabies to other animals and humans.

A systematic review on the pathogenesis of death due to COVID-19

Background: A pandemic COVID-19 affected the whole world since December 2019. By this review an attempt is made to find the pathogenesis behind the death of patients from the available literature on post-mortem findings. A trial is made to find out suitable Homoeopathic medicines based on pathological findings.Methods: Eight research articles having the post-mortem findings of deceased due to COVID-19 are selected and a review is done with statistical analysis to find the prevalence of pathogenesis. Results: Ground glass opacity is the common finding in chest imaging, virus like particles is seen in the lung parenchyma and the prevalent pathogenesis is found to be Diffuse Alveolar Damage (81.93%) of the lung tissue. Arsenicum album is found to be the leading remedy. Conclusion: The prevalent pathological finding is found to be Diffuse Alveolar Damage in the lungs which is a feature consistent with fatal viral infection leading to Acute Respiratory Distress Syndrome.

Rabies and the Heart.

As one of the neglected diseases, rabies is as a highly fatal viral infection, most prevalent in low- and middle-income regions, which produces a substantial health and economic burden. It mainly affects the central nervous system causing encephalitis, however extraneuronal involvement has been documented. Cardiac structures may be involved and can play a role in the severity of the disease. Most of the existing literature comes from case reports and case series where cardiac involvement results in myocarditis and cardiac arrhythmias. As part of the “Neglected Tropical Diseases and Other Infectious Diseases Involving the Heart” (NET-HEART Project), the objective of this article is to review all the information available on the cardiac involvement of this disease.

Kırım Kongo Kanamalı Ateşi Tanısıyla İzlenen Hastaların Epidemiyolojik ve Biyokimyasal Olarak Değerlendirilmesi

Aim: Crimean-Congo Hemorrhagic Fever (CCHF) is a viral hemorrhagic fever. To evaluate the clinical, epidemiological and laboratory characteristics of patients with CCHF. &#x0D; Methods: This study was performed with adult patients under monitoring with diagnosis of CCHF at the Atatürk University Faculty of Medicine Infectious Diseases Clinic between April 2012 and August 2013. &#x0D; Results: Diagnosis of CCHF was based on presence of Enzyme-linked immunosorbent assay (ELISA) anti-CCFV IgM and/or virus antigen at Refik Saydam Hygiene Center (RSHM) in patient serum and/or real time Polymerase Chain Reaction (PCR). One hundred twenty-one cases were included. Fifty-eight (48.7%) of patients were male and 62(51.2%) female, with a mean age of 50.04 ± 18.22 (16-86) years. Contact with ticks was determined in 62.8% of patients. Length of incubation was 3.9±2.7 days. Five patients (4.1%) died. &#x0D; Conclusion: CCHF which is carried by ticks is a fatal viral infection. The most important factor in protection is the prevention of tick contact. People living in endemic regions must be educated and instructed how to perform daily tick checks. Patients have got high fever, myalgia, headache and tick bite must be asked in history. We believe that early diagnosis and treatment of CCHF cases may significantly reduce morbidity and mortality.

The Controversy on the Role of ACE2 Receptor in COVID-19 Infection: The Protective Shift toward the ACE2 Axis

Background: Angiotensin-converting enzyme 2 (ACE2) is recognized as the main cellular receptor for the new coronavirus, SARS-CoV-2, that facilitates its entry into the host target cell, leading to the fatal viral infection, coronavirus disease 2019 (COVID-19). Thus, it is considered as a main therapeutic target in the SARS-CoV-2 infection. The dual role of ACE2 as a gate for SARS-CoV-2 virus and as a part of lung and multi-organ protection has built a scientific debate that affects the choice of treatments used against COVID-19 patient. ACE2 inhibitors like anti-ACE2 antibodies were first introduced as therapeutic solutions that, theoretically, would decrease the availability of target molecules for SARS-CoV-2 by downregulating ACE2 expression. However, animal studies showed that ACE2 upregulation acts as a counterbalance to the hypertensive pro-inflammatory angiotensin I-converting enzyme (ACE) in the renin–angiotensin system (RAS) and results in a protective role against acute lung injury – a fatal consequence of the disease. The current study tests the effect of ACE2-activating treatments against the outcome of genetic variations in the population that have ACE2-upregulatory effects.&#x0D; Conclusion Despite its role as a receptor for the SARS-CoV-2 virus, experimental studies and the genetic polymorphisms in populations that have ACE2 upregulation revealed a protective role against COVID-19 infection.&#x0D; &#x0D; Key words: ACE2 ACE COVID-19 treatments genetic variations

Human rabies exposure outbreak investigation in Tembaro district, Ethiopia, 2018

Background: Rabies is a fatal viral infection that can infect all mammals. It poses a significant health problem in most of African countries including Ethiopia, where the majority of the cases result from dog bites. This study was conducted to assess the extent of the outbreak, to identify the exposing animals and risk factors for the transmission and to give technical support in the control and prevention measures. Methods and materials: Cross-sectional descriptive study design was used to conduct the study from April 28 to May 16, 2018. Line list of human exposure to rabies cases were collected from health facility. Case detection was actively done in the community. Structured questionnaire was used to assess awareness of the victims regarding rabies. Results: A total of 125 suspected rabies exposures and 9 suspected human rabies deaths were found. The rabies exposure crude attack rate (AR) was 90 per 100000 populations at risk. Age groups 15 to 45 were the most affected with age specific AR of 124 per 100000 populations. The highest AR occurred in Keleta kebele with AR of 85/10,000 population. Dogs, cats, donkeys, foxes, hyena and bat were found the responsible exposing animals. However; dogs were the most common, being responsible for 62 (50%) of the exposures. Among the dogs, 45/62 (72.5%) of them were stray dogs. Among the owned dogs, 54(88%) were not vaccinated. Brain tissue from two dogs was tested and became positive for rabies by Fluorescent Antibody Test (FAT). Among 95 victims interviewed about rabies, only 33 (37%) of them know the symptoms, transmission, and prevention methods of rabies. Conclusion: There was high number of human rabies exposure due to animal bites in Tembaro district. Wild lives escaped from the forests around the Gibe river basin and high prevalence of free roaming and unvaccinated dogs were the likely risk factors for the increment of the rabies exposure. Inter-sectoral collaboration is needed among the district health office, wild life and environmental protection office and the livestock and fishery resource office. Mass dog vaccination and awareness creation in the community about rabies exposure are recommended.

Human rabies exposure outbreak investigation in Tembaro district, Ethiopia, 2018

Background: Rabies is a fatal viral infection that can infect all mammals. It poses a significant health problem in most of African countries including Ethiopia, where the majority of the cases result from dog bites. This study was conducted to assess the extent of the outbreak, to identify the exposing animals and risk factors for the transmission and to give technical support in the control and prevention measures. Methods and materials: Cross-sectional descriptive study design was used to conduct the study from April 28 to May 16, 2018. Line list of human exposure to rabies cases were collected from health facility. Case detection was actively done in the community. Structured questionnaire was used to assess awareness of the victims regarding rabies. Results: A total of 125 suspected rabies exposures and 9 suspected human rabies deaths were found. The rabies exposure crude attack rate (AR) was 90 per 100,000 populations at risk. Age groups 15–45 were the most affected with age specific AR of 124 per 100,000 populations. The highest AR occurred in Keleta kebele with AR of 85/10,000 population. Dogs, cats, donkeys, foxes, hyena and bat were found the responsible exposing animals. However; dogs were the most common, being responsible for 62 (50%) of the exposures. Among the dogs, 45/62 (72.5%) of them were stray dogs. Among the owned dogs, 54(88%) were not vaccinated. Brain tissue from two dogs was tested and became positive for rabies by Fluorescent Antibody Test (FAT). Among 95 victims interviewed about rabies, only 33 (37%) of them know the symptoms, transmission, and prevention methods of rabies. Conclusion: There was high number of human rabies exposure due to animal bites in Tembaro district. Wild lives escaped from the forests around the Gibe river basin and high prevalence of free roaming and unvaccinated dogs were the likely risk factors for the increment of the rabies exposure. Inter-sectoral collaboration is needed among the district health office, wild life and environmental protection office and the livestock and fishery resource office. Mass dog vaccination and awareness creation in the community about rabies exposure are recommended.

Stay Home: Role of Physical Exercise Training in Elderly Individuals' Ability to Face the COVID-19 Infection.

Recently, the novel coronavirus epidemic occurred in China and spread worldwide to become a global pandemic. COVID-19 is a fatal viral infection causing death, particularly in aged individuals, due to impaired immunity. To date, no intervention is available to prevent COVID-19 and its manifestations. Physical exercise training generally has health benefits, and it assists in the prevention of several chronic diseases. Therefore, this review is aimed at exploring the role of physical exercise training in the face of COVID-19 in older adults and elderly individuals. From this point of view, this review suggests that physical exercise training plays a key role in promoting immune system regulation, delaying immunity dysfunction, reducing circulatory inflammation markers, and preventing sarcopenia and thus could prevent the risk of acquiring COVID-19 infection and reduce the complications of recommended self-isolation in older adults and elderly individuals. Additionally, immunity biomarkers were optimistically demonstrated in older adults following physical exercise training, thereby reducing mortality and morbidity rates. Finally, in accordance with recommendations to stay home and perform self-isolation to prevent the spread of COVID-19, all populations are strongly recommended to practice regular home exercise training at home to promote immune system functioning.

Predictors of Death Rate during the COVID-19 Pandemic.

Coronavirus (COVID-19) is a potentially fatal viral infection. This study investigates geography, demography, socioeconomics, health conditions, hospital characteristics, and politics as potential explanatory variables for death rates at the state and county levels. Data from the Centers for Disease Control and Prevention, the Census Bureau, Centers for Medicare and Medicaid, Definitive Healthcare, and USAfacts.org were used to evaluate regression models. Yearly pneumonia and flu death rates (state level, 2014–2018) were evaluated as a function of the governors’ political party using a repeated measures analysis. At the state and county level, spatial regression models were evaluated. At the county level, we discovered a statistically significant model that included geography, population density, racial and ethnic status, three health status variables along with a political factor. A state level analysis identified health status, minority status, and the interaction between governors’ parties and health status as important variables. The political factor, however, did not appear in a subsequent analysis of 2014–2018 pneumonia and flu death rates. The pathogenesis of COVID-19 has a greater and disproportionate effect within racial and ethnic minority groups, and the political influence on the reporting of COVID-19 mortality was statistically relevant at the county level and as an interaction term only at the state level.