Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness - United States and Puerto Rico, April 2020-March 2021.

The diagnosis of dengue disease, caused by the dengue virus (DENV) (a flavivirus), often requires serologic testing during acute and early convalescent phases of the disease. Some symptoms of DENV infection, such as nonspecific fever, are similar to those caused by infection with SARS-CoV-2, the virus that causes COVID-19. In studies with few COVID-19 cases, positive DENV immunoglobulin M (IgM) results were reported with various serologic tests, indicating possible cross-reactivity in these tests for DENV and SARS-CoV-2 infections (1,2). DENV antibodies can cross-react with other flaviviruses, including Zika virus. To assess the potential cross-reactivity of SARS-CoV-2, DENV, and Zika virus IgM antibodies, serum specimens from 97 patients from Puerto Rico and 12 U.S.-based patients with confirmed COVID-19 were tested using the DENV Detect IgM Capture enzyme-linked immunosorbent assay (ELISA) (InBios International).* In addition, 122 serum specimens from patients with confirmed dengue and 121 from patients with confirmed Zika virus disease (all from Puerto Rico) were tested using the SARS-CoV-2 pan-Ig Spike Protein ELISA (CDC).† Results obtained for DENV, Zika virus IgM, and SARS-CoV-2 antibodies indicated 98% test specificity and minimal levels of cross-reactivity between the two flaviviruses and SARS-CoV-2. These findings indicate that diagnoses of dengue or Zika virus diseases with the serological assays described in this report are not affected by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.

A new approach to implementing decentralized wastewater treatment concepts.

Planners and decision-makers in the wastewater sector are often confronted with the problem of identifying adequate development strategies and most suitable finance schemes for decentralized wastewater infrastructure. This paper research has focused on providing an approach in support of such decision-making. It is based on basic principles that stand for an integrated perspective towards sustainable wastewater management. We operationalize these principles by means of a geographic information system (GIS)-based approach 'Assessment of Local Lowest-Cost Wastewater Solutions'--ALLOWS. The main product of ALLOWS is the identification of cost-effective local wastewater management solutions for any given demographic and physical context. By using universally available input data the tool allows decision-makers to compare different wastewater solutions for any given wastewater situation. This paper introduces the ALLOWS-GIS tool. Its application and functionality are illustrated by assessing different wastewater solutions for two neighboring communities in rural Jordan.

Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for 7 tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the 5 best performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9-16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the 4 best performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to Zika virus. For the detection of previous DENV infections the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation.

A Deceptively Unremarkable Standstill: A Case Report of a Rare Cardiac Electrophysiologic Event.

Ventricular standstill is a rare cardiac event associated with a high mortality. It is considered a ventricular fibrillation equivalent. The longer the duration, the poorer the prognosis. It is therefore unusual for an individual to have recurrent episodes of standstill and survive, without morbidity and rapid mortality. Here, we report the unique case of a 67-year-old male, previously diagnosed with heart disease, requiring intervention, who lived with recurrent syncopal episodes for a decade. Though such occurrences have previously been documented, we seek to stress the importance of using clinical tools in assessing what could easily have been passed off as orthostatic in origin.

Systemic cytomegalovirus masquerading as a colorectal mass in a patient with undiagnosed HIV/AIDS.

Introduction: Cytomegalovirus (CMV) infection is common among patients with human immunodeficiency virus (HIV) infection. Gastrointestinal (GI) involvement with tumor like lesion is a rare presentation. Our patient presented with rectal pain and findings concerning for malignancy. Subsequently our patient was diagnosed with acquired immunodeficiency syndrome (AIDS), CMV viremia and CMV proctitis. Case: A 37-year-old man who reported having sex with men presented with severe proctalgia and hematochezia. Imaging showed irregular rectal wall thickening concerning for malignancy. Sigmoidoscopy revealed a circumferential necrotic lesion suspicious for malignancy. Surprisingly, biopsy showed a cytopathic effect compatible with CMV infection. In addition to testing positive for CMV, patient was newly diagnosed with HIV/AIDS, hepatitis C, syphilis, and gonorrhea. CMV infection was treated with ganciclovir, which resulted in a significant response. Ganciclovir was later replaced with valganciclovir. Valganciclovir was continued and antiretroviral therapy (ART) was started as an outpatient and with resolution of symptoms. Discussion: CMV infection is one of the most common opportunistic infections among patients with HIV infection. Several cases of CMV colitis were reported among immunocompromised patients. Our patient's presenting symptoms and direct visualization of rectal lesion were not only deceptive but also unique. As what looked like a rectal malignancy was later diagnosed as tissue invasive CMV by biopsy. Invasive CMV infection should be managed with ganciclovir. Conclusion: GI CMV as the initial presentation of HIV is rare. Moreover, CMV proctitis can masquerade as a rectal cancer and clinicians should be aware of this rare presentation of CMV.

Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation.

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including in the CNS and the immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric patients with MS compared with controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid, tauroursodeoxycholic acid (TUDCA), on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and proinflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced the severity of disease through its effects on G protein-coupled bile acid receptor 1 (GPBAR1). We demonstrate that bile acid metabolism was altered in MS and that bile acid supplementation prevented polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorated neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.

Quetiapine has an additive effect to triiodothyronine in inducing differentiation of oligodendrocyte precursor cells through induction of cholesterol biosynthesis.

Multiple sclerosis (MS) is characterized by demyelinated lesions in the central nervous system. Destruction of myelin and secondary damage to axons and neurons leads to significant disability, particularly in people with progressive MS. Accumulating evidence suggests that the potential for myelin repair exists in MS, although for unclear reasons this process fails. The cells responsible for producing myelin, the oligodendrocytes, and their progenitors, oligodendrocyte precursor cells (OPCs), have been identified at the site of lesions, even in adults. Their presence suggests the possibility that endogenous remyelination without transplantation of donor stem cells may be a mechanism for myelin repair in MS. Strategies to develop novel therapies have focused on induction of signaling pathways that stimulate OPCs to mature into myelin-producing oligodendrocytes that could then possibly remyelinate lesions. We have been investigating pharmacological approaches to enhance OPC differentiation, and have identified that the combination of two agents, triiodothyronine (T3) and quetiapine, leads to an additive effect on OPC differentiation and consequent myelin production via both overlapping and distinct signaling pathways. While the ultimate production of myelin requires cholesterol biosynthesis, we identified that quetiapine enhances gene expression in this pathway more potently than T3. Two blockers of cholesterol production, betulin and simvastatin, reduced OPC differentiation into myelin producing oligodendrocytes. Elucidating the nature of agents that lead to complementary and additive effects on oligodendrocyte differentiation and myelin production may pave the way for more efficient induction of remyelination in people with MS.

Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination.

Oligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination.

Survival of Endodontically Treated Roots/Teeth Based on Periapical Health and Retention: A 10-year Retrospective Cohort Study.

INTRODUCTION: The purpose of this retrospective longitudinal cohort study was to evaluate the outcome of nonsurgical root canal treatment (NSRCT), expressed as survival for both periapical health and retention of roots/teeth, as determined by clinical evaluation, periapical film/digital radiography (PFR/DPR), and cone-beam computed tomography (CBCT) over 10 years, to determine the prognostic factors that influenced successful treatment outcomes. METHODS: A total of 132 teeth (208 roots) with vital pulp received NSRCT at a university clinic. Eighteen factors (preoperative, intraoperative, and postoperative) were documented from the dental records and radiographs. Periapical indices with scores ≥2 (PFR/DPR) and ≥1 (CBCT) indicated the presence of a periapical lesion. Data were analyzed using the Kaplan-Meier test and the Cox proportional hazards regression model (P < .05). RESULTS: The estimated 10-year overall survival rates for periapical health of roots/teeth were 89.4%/88.6% with PFR, 89.4%/89.3% with DPR, and 72.6%/69.7% with CBCT; the survival rate for root/tooth retention was 90.4%/91.6%. CONCLUSIONS: The long-term outcome of NSRCT expressed as survival for periapical health was different with each radiographic method. Approximately more than 90% of the roots/teeth were retained for up to 10 years. The prognostic factors for periapical health were the disinfection of gutta-percha, missed canals, age, treatment sessions, and density of root filling (voids); the age and presence of a post were for root/tooth retention.

In situ synchrotron radiation X-ray scattering study on the effect of a stearic sucrose ester on polymorphic behavior of a new sunflower oil variety.

The effect of the stearic sucrose ester (SE) S-170 on crystallization behavior and polymorphism of two stearins obtained from a new variety of high stearic high oleic sunflower oil was studied by pulsed nuclear magnetic resonance (p-NMR), small (SAXS) and wide (WAXS) angle X-ray scattering using synchrotron light and differential scanning calorimetry (DSC). p-NMR studies showed that there is always a crystallization temperature below which SE S-170 accelerated crystallization and above which SE S-170 delayed nucleation and growth. The effect of SE S-170 strongly depended on supercooling. It was efficient as a seed for high supercooling (low crystallization temperatures) but this efficiency diminished at low supercooling (temperatures close to the melting point) when few crystals were formed. SAXS and WAXS results demonstrated that depending on crystallization temperature SE S-170 promoted crystallization of α and ß forms with more polymorphic similarity and inhibited occurrence of ß' forms especially the ß'2 polymorph. However, in some conditions SE S-170 favored crystallization of ß'1 polymorph. DSC experiments showed that SE S-170 significantly diminished total melting enthalpies when the effect was a delay in crystallization. For other conditions no significant differences were found in melting temperatures or total melting enthalpies. When stearins were stored at 25°C, crystallization in the ß2 form was promoted. Depending on crystallization temperature, polymorphic forms ß'1 and ß2 may be obtained as the main polymorphic forms. This is very relevant from the technological point of view. Depending on the application, SE S-170 may help obtain the required polymorphic form: ß'1 form for spreads and ß2 polymorph for chocolate production.

Inmunohistoquímica en patología de mama: diferenciación de lesiones complejas benignas y malignas de mama: un reporte de caso y revisión de la literatura / Immunohistochemistry in breast pathology: differentiating complex benign and malign breast lesions: a case report and literature review

Objetivo: revisar las bases histológicas y los criterios diagnósticos diferenciales de la aplicación de la inmunohistoquímica en la patología mamaria. Caso clínico : se presenta el caso de una paciente con lesión mamaria esclerosante compleja, tipo adenosis microglandular (MGA), que requirió el uso de inmunohistoquímica como técnica auxiliar para diferenciar la lesión de un adenocarcinoma de mama in situ, y definir así el tratamiento. Materiales y métodos: se realizó una búsqueda de la información en las bases de datos Medline vía PubMed, SciELO y en libros de la especialidad. Se reportaron 25 títulos, 12 correspondían con el tema: 4 reportes de caso, 1 con revisión de la literatura, una carta al editor y 7 artículos relacionados de forma más general con el tema. Conclusión: la inmunohistoquímica permite hacer el diagnóstico diferencial de las lesiones mamarias complejas, como la adenosis esclerosante y el cáncer de mama in situ o microinvasor.

Objective: reviewing the histological basis and differential diagnostic criteria for applying immunohistochemistry in breast pathology. Clinical case: the case of a patient suffering from complex sclerosing lesion (CSL) of the breast, microglandular adenosis (MGA) pattern is presented; she required immunohistochemistry as an auxiliary technique for differentiating an adenocarcinoma-related breast lesion in situ and thus defining its treatment. Materials and methods: a search was made of the pertinent information in Medline databases via PubMed, SciELO and in books on the specialty; 25 titles were reported, 12 of them corresponding to the immediate topic: 4 were case reports with a literature review and one was a letter to the editor. 7 articles dealt with the topic in a more general way. Conclusion: immunohistochemistry led to the differential diagnosis of complex breast lesions such as sclerosing adenosis, and in situ or microinvase breast cancer.

Degeneración sarcomatosa rápida de un leiomioma simplástico pleomórfico de útero, reporte de caso y revisión de la literatura / Rapid sarcomatous degeneration of an uterine pleomorphic symplastic leiomyoma

Objetivo: revisar la epidemiología y el cuadro histopatológico de los sarcomas uterinos. Presentación del caso: mujer de 35 años de edad atendida en el Hospital General de Medellín (Hospital de 3er nivel de atención, público, centro de referencia Obstétrica), por sangrado genital. Presentaba anemia y masa pélvica, que en el estudio histopatológico mostró como leiomiosarcoma uterino de alto grado. Discusión: se describe como una lesión tumoral benigna atípica con celularidad variable, degenera en una lesión leiomiosarcoma de comportamiento agresivo, con intervalo de ataques de síntomas en fase temprana.