Adeno-associated virus type 2 in US children with acute severe hepatitis.

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

One-year incidence, predictors, and accuracy of prediction of suicidal thoughts and behaviors from the first to second year of university.

BACKGROUND: Research is scarce on the prospective predictors of first onset suicidal thoughts and behaviors (STB) and the accuracy of these predictors in university students, particularly in low-and-middle income countries. Therefore, we assessed the 1-year incidence of STB among first-year students, a broad range of prospective predictors of STB incidence, and evaluated the prediction accuracy of a baseline multivariate risk prediction model to identify students at highest risk for STB onset over the subsequent 12 months. METHODS: Students (n = 3238) from 13 universities in Mexico completed an online survey developed for the World Mental Health International College Student Surveys in their first year and again 12 months after. We ran generalized linear models and receiver operator curves. RESULTS: The 1-year incidence of suicidal ideation, plan and attempt was 8.53%, 3.75%, and 1.16%, respectively. Predictors in final models were female sex (ideation only), minority sexual orientation (ideation only), depression, eating disorders, ADHD (ideation and plan), ongoing arguments or breakup with a romantic partner (ideation only), emotional abuse (ideation only), parental death (ideation, plan), not Catholic/Christian (ideation, plan), not having someone to rely on, psychotic experiences (plan only), and insufficient sleep (attempt only). Prediction accuracy for ideation, plan and attempt was area under the curve = 0.76, 0.81 and 0.78, respectively. Targeting the top 10% of students at highest risk could reduce STB in the subsequent year up to 36%. CONCLUSIONS: By assessing these risk/protective factors in incoming students we identified students at greatest risk for developing STB to whom suicide prevention strategies could be targeted.

The Stability of an Isolate of the SARS-CoV-2 B.1.1.7 Lineage in Aerosols Is Similar to 3 Earlier Isolates.

BACKGROUND: Our laboratory previously examined the influence of environmental conditions on the stability of an early isolate of SARS-CoV-2 (hCoV-19/USA/WA-1/2020) in aerosols generated from culture medium or simulated saliva. However, genetic differences have emerged among SARS-CoV-2 lineages, and it is possible that these differences may affect environmental stability and the potential for aerosol transmission. METHODS: The influence of temperature, relative humidity, and simulated sunlight on the decay of 4 SARS-CoV-2 isolates in aerosols, including 1 belonging to the recently emerged B.1.1.7 lineage, were compared in a rotating drum chamber. Aerosols were generated from simulated respiratory tract lining fluid to represent aerosols originating from the deep lung. RESULTS: No differences in the stability of the isolates were observed in the absence of simulated sunlight at either 20°C or 40°C. However, a small but statistically significant difference in the stability was observed between some isolates in simulated sunlight at 20°C and 20% relative humidity. CONCLUSIONS: The stability of SARS-CoV-2 in aerosols does not vary greatly among currently circulating lineages, including B.1.1.7, suggesting that the increased transmissibility associated with recent SARS-CoV-2 lineages is not due to enhanced survival in the environment.

Toluene toxicity presenting with hypokalemia, profound weakness and U waves in the electrocardiogram.

We present the case of a 25-year-old man with progressive limb weakness. His electrocardiogram showed prominent U waves which made us consider hypokalemia. The final diagnosis was toluene intoxication with severe hypokalemia and metabolic acidosis. Intravenous potassium administration and hydration effectively corrected the electrolyte and acid-base alterations; weakness resolved and the patient was discharged. The approach to a patient with acute weakness can be challenging. This case reminds us that the electrocardiogram can be a valuable tool in the evaluation and differential diagnosis of patients presenting to the emergency department with these conditions.

Periodicity of the growth-band formation in vertebrae of juvenile scalloped hammerhead shark Sphyrna lewini from the Mexican Pacific Ocean.

The age of 296 juvenile scalloped hammerhead sharks Sphyrna lewini caught by several fisheries in the Mexican Pacific Ocean from March 2007 to September 2017 were estimated from growth band counts in thin-sectioned vertebrae. Marginal-increment analysis (MIA) and centrum-edge analysis (CEA) were used to verify the periodicity of formation of the growth bands, whereas elemental profiles obtained from LA-ICP-MS transect scans in vertebrae of 15 juveniles were used as an alternative approach to verify the age of the species for the first time. Age estimates ranged from 0 to 10+ years (42-158.7 cm total length; LT ). The index of average percentage error (IAPE 3.6%), CV (5.2%), bias plots and Bowker's tests of symmetry showed precise and low-biased age estimation. Both MIA and CEA indicated that in the vertebrae of juveniles of S. lewini a single translucent growth band was formed during winter (November-March) and an opaque band during summer (July-September), a period of faster growth, apparently correlated with a higher sea surface temperature. Peaks in vertebral P and Mn content spatially corresponded with the annual banding pattern in most of the samples, displaying 1.19 and 0.88 peaks per opaque band, respectively, which closely matched the annual deposition rate observed in this study. Although the periodicity of growth band formation needs to be verified for all sizes and ages representing the population of the species in the region, this demonstration of the annual formation of the growth bands in the vertebrae of juveniles should lead to a re-estimation of the growth parameters and productivity of the population to ensure that it is harvested at sustainable levels.

Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

Sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is the sudden unexpected death of a child younger than one year during sleep that cannot be explained after a postmortem evaluation including autopsy, a thorough history, and scene evaluation. The incidence of SIDS has decreased more than 50% in the past 20 years, largely as a result of the Back to Sleep campaign. The most important risk factors relate to the sleep environment. Prone and side sleeping positions are significantly more dangerous than the supine position. Bed sharing with a parent is strongly correlated with an increased risk of SIDS, especially in infants younger than 12 weeks. Apparent life-threatening events are not a risk factor for SIDS. Parents should place infants on their backs to sleep, should not share a bed, and should avoid exposing the infant to tobacco smoke. Other risk-reducing measures include using a firm crib mattress, breastfeeding, keeping vaccinations up to date, avoiding overheating due to overbundling, avoiding soft bedding, and considering the use of a pacifier during sleep once breastfeeding is established. One consequence of the Back to Sleep campaign is a significant increase in the incidence of occipital flattening. Infants who develop a flat spot should be placed with the head facing alternating directions each time he or she is put to bed. Supervised prone positioning while the infant is awake, avoiding excessive use of carriers, and upright positioning while awake are also recommended.

[A case study of anaphylaxis in a pregnant woman]. / Choque anafiláctico en una gestante en el tercer trimestre de embarazo.

We report a case of anaphylaxis in a 35+5 week of pregnancy patient who came to the Emergency Room with shortness of breath, hypotension and loss on fetal wellbeing. Due to her medical history and given the clinical picture at that time, an anaphylactic shock was suggested as the most probable diagnose. The administration of dexchlorpheniramine and methylprednisolone resulted in an immediate and positive reaction. Simultaneously, an improvement in the fetus cardiotocographic record was objectified. The patient was hospitalized for 48 hours, after which she was discharged. In case of suspicion of anaphylaxis in a pregnant woman, four aspects should be handled: the severity of the anaphylaxis chart, individual complications regarding a pregnant woman, unfavorable effects of the regularly used treatment during that specific gestation, and the need of fetal extraction based of gestational age.

Ecotoxicological evaluation of chitosan biopolymer films particles in adult zebrafish (Danio rerio): A comparative study with polystyrene microplastics.

To mitigate the environmental impact of microplastics (MPs), the scientific community has innovated sustainable and biodegradable polymers as viable alternatives to traditional plastics. Chitosan, the deacetylated form of chitin, stands as one of the most thoroughly investigated biopolymers and has garnered significant interest due to its versatile applications in both medical and cosmetic fields. Nevertheless, there is still a knowledge gap regarding the impact that chitosan biopolymer films (CBPF) may generate in aquatic organisms. In light of the foregoing, this study aimed to assess and compare the potential effects of CBPF on the gastrointestinal tract, gills, brain, and liver of Danio rerio against those induced by MPs. The findings revealed that both CBPF and MPs induced changes in the levels of oxidative stress biomarkers across all organs. However, it is essential to note that our star plots illustrate a tendency for CBPF to activate antioxidant enzymes and for MPs to produce oxidative damage. Regarding gene expression, our findings indicate that MPs led to an up-regulation in the expression of genes associated with apoptotic response (p53, casp3, cas9, bax, and bcl2) in all fish organs. Meanwhile, CBPF produced the same effect in genes related to antioxidant response (nrf1 and nrf2). Overall, our histological observations substantiated these effects, revealing the presence of plastic particles and tissue alterations in the gills and gastrointestinal tract of fish subjected to MPs. From these results, it can be concluded that CBPF does not represent a risk to fish after long exposure.

Internet Gaming Disorder and the Incidence of Suicide-Related Ideation and Behaviors in College Students.

OBJECTIVES: The longitudinal associations between DSM-5 Internet Gaming Disorder (IGD) and suicide-related ideation and behaviors have not been explored. In this study, we therefore seek to examine the association between baseline IGD and incident suicide ideation, plans, and attempts. METHODS: This is a prospective cohort study of 2586 Mexican college students followed up from September 2018 to June 2022. We estimated hazards ratios modeling incidence of suicide ideation, plans, and attempts by fitting proportional hazards Cox models with person-time scaled in years. RESULTS: Among 2140 students without suicide ideation at baseline, there were 467 incident cases in 3987.6 person-years; ideation incidence rates were 179 cases per 1000 person-years among students with IGD and 114 cases per 1000 person-years among those without IGD. Incidence rates for suicide plans were 67 and 39 per 1000 among IGD and non-IGD students, and 15 and 10 per 1000, respectively for attempts. After controlling for age, sex, and mood, anxiety, and substance use disorders, IGD was associated with an 83% increased risk of suicide ideation. Although incidence rate estimates for plans and attempts were higher among students with IGD, results were not statistically significant. CONCLUSIONS: This study helps to raise awareness of the increased risk of at least suicidal ideation in people experiencing IGD. Clinicians treating patients with IGD may encounter complaints of suicide ideation over time, and even reports of suicidal behavior that should not be disregarded. Identifying these patients and treating/referring them for underlying suicidality should form part of IGD treatment.

Point of care thoracic ultrasound versus chest computed tomography in the approach of febrile neutropenia patients: A diagnostic accuracy cohort study.

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.

Amniotic fluid pulmonary embolism and COVID-19: Case report.

Amniotic fluid embolism is a rare complication of peripartum. It is caused by the entry of fetal components into the maternal systemic circulation. There are 2 main types: typical; it presents with the triad of hemodynamic collapse, respiratory distress and disseminated intravascular coagulation type coagulopathy, while atypical; disseminated intravascular coagulation does not occur. SARS CoV-2 infection causes coagulopathy due to the alteration of Virchow's triad and coagulation factors. We present the case of a 21-year-old pregnant woman who consulted for premature rupture of membranes, with an indication for cesarean section, and during surgery presented bradycardia, hypotension, and desaturation until cardiorespiratory arrest. An angiotomography showed amniotic fluid embolism associated with pulmonary edema, ruling out differential diagnoses associated with the disease, leaving as the only cause of the infection confirmed by COVID-19, which, it was inferred, was closely related to the immunological disorder suffered by the patient.

Influence of sucralose, acesulfame-k, and their mixture on brain's fish: A study of behavior, oxidative damage, and acetylcholinesterase activity in Daniorerio.

Sucralose (SUC) and acesulfame-k (ACE-K) are widely used artificial sweeteners worldwide; however, they are frequently detected in aquatic environments due to their low metabolism and inadequate removal during wastewater treatment. The harmful effects of these compounds on hydrobionts have yet to be fully understood, as data on their toxicity is limited and inconclusive. This research aimed to determine the impact of SUC (50, 75, 125 µg/L) and ACE-K (50, 75, 125 µg/L), individually and in combination, on fish's swimming behavior, acetylcholinesterase activity, and oxidative stress response after four months of exposure. Following exposure, adult Danio rerio displayed anxiety-like behavior, as evidenced by increased freezing time and decreased swimming activity. Additionally, analysis of fish brain tissue revealed a disruption of REDOX homeostasis, leading to oxidative stress, which may be responsible for the observed inhibition of AChE activity. The results indicated that ACE-K was more toxic than SUC, and the mixture of both compounds produced a more detrimental effect than when each compound was administered alone. These findings highlight the hazardous impacts of SUC and ACE-K on fish in environmentally relevant concentrations, suggesting that these compounds should be added to the priority pollutant list.

Prevalence of African animal trypanosomiasis among livestock and domestic animals in Uganda: a systematic review and meta-regression analysis from 1980 to 2022.

African animal trypanosomiasis (AAT) is one of the major constraints to animal health and production in sub-Saharan Africa. To inform AAT control in Uganda and help advance along the progressive control pathway (PCP), we characterized AAT prevalence among eight host species in Uganda and explored factors that influence the prevalence variation between studies. We retrieved AAT prevalence publications (n = 2232) for Uganda (1980-2022) from five life sciences databases, focusing on studies specifying AAT detection methods, sample size, and the number of trypanosome-positive animals. Following PRISMA guidelines, we included 56 publications, and evaluated publication bias by the Luis Furuya-Kanamori (LFK) index. National AAT prevalence under DNA diagnostic methods for cattle, sheep and goats was 22.15%, 8.51% and 13.88%, respectively. Under DNA diagnostic methods, T. vivax was the most common Trypanosoma sp. in cattle (6.15%, 95% CI: 2.91-10.45) while T. brucei was most common among small ruminants (goats: 8.78%, 95% CI: 1.90-19.88, and sheep: 8.23%, 95% CI: 4.74-12.50, respectively). Northern and Eastern regions accounted for the highest AAT prevalence. Despite the limitations of this study (i.e., quality of reviewed studies, underrepresentation of districts/regions), we provide insights that could be used for better control of AAT in Uganda and identify knowledge gaps that need to be addressed to support the progressive control of AAT at country level and other regional endemic countries with similar AAT eco-epidemiology.

Management of Nail Disease in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Nail psoriasis is common, impairs fine motor finger functioning, affects cosmesis, and is associated with a lower quality of life. This review updates the previous Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for nail psoriasis. METHODS: This systematic literature review of the PubMed, MEDLINE, Embase, and Cochrane databases examined the updated evidence since the last GRAPPA nail psoriasis treatment recommendations published in 2014. Recommendations are based on preformed PICO (Patient/Population - Intervention - Comparison/Comparator - Outcome) questions formulated by an international group of dermatologists, rheumatologists, and patient panel members. Data from this literature review were evaluated in line with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: Overall, there is insufficient evidence to make any recommendation for the use of topical corticosteroids, topical calcipotriol, topical tazarotene, topical cyclosporine, dimethyl fumarates/fumaric acid esters, phototherapy, and alitretinoin. There is a low strength of evidence to support the use of calcipotriol and corticosteroid preparations, topical tacrolimus, oral cyclosporine, oral methotrexate, intralesional corticosteroids, pulsed dye laser, acitretin, Janus kinase inhibitors, and apremilast. CONCLUSION: The highest strength of supporting evidence is for the recommendation of biologic agents including tumor necrosis factor inhibitors, and interleukin 12/23, 17, and 23 inhibitors.

Repetitive peptide boosting progressively enhances functional memory CTLs.

Cytotoxic T lymphocytes (CTLs) play a critical role in controlling intracellular pathogens and cancer cells, and induction of memory CTLs holds promise for developing effective vaccines against critical virus infections. However, generating memory CTLs remains a major challenge for conventional vector-based, prime-boost vaccinations. Thus, it is imperative that we explore nonconventional alternatives, such as boosting without vectors. We show here that repetitive intravenous boosting with peptide and adjuvant generates memory CD8 T cells of sufficient quality and quantity to protect against infection in mice. The resulting memory CTLs possess a unique and long-lasting effector memory phenotype, characterized by decreased interferon-γ but increased granzyme B production. These results are observed in both transgenic and endogenous models. Overall, our findings have important implications for future vaccine development, as they suggest that intravenous peptide boosting with adjuvant following priming can induce long-term functional memory CTLs.

Familial chylomicronemia syndrome: The first case reported in Ecuador. / Síndrome de quilomicronemia familiar: primer caso reportado en Ecuador.

Familial chylomicronemia syndrome (FCS) is a genetic entity with autosomal recessive inheritance. Mutations in genes (such as APOC2, APOAV, LMF-1, GPIHBP-1) that code for proteins that regulate the maturation, transport, or polymerization of lipoprotein lipase-1 are the most common causes, but not the only ones. The objective of this study was to report the first documented case in Ecuador. CLINICAL CASE: A 38-year-old man presented with chronic hepatosplenomegaly, thrombocytopenia, pancreatic atrophy, and severe hypertriglyceridemia refractory to treatment. A molecular analysis was performed by next generation sequencing that determined a deficiency of Lipoprotein Lipase OMIM #238600 in homozygosis. Genetic confirmation is necessary in order to establish the etiology of HTGS for an adequate management of this pathology.

Severe hypertriglyceridemia secondary to splice-site and missense variants in LMF1 in three patients from Ecuador.

Rare pathogenic variants in the LMF1 gene, which encodes lipase maturation factor 1, are a minor cause of familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia. In this report we present three adult patients, all of them born and raised in Quito, Ecuador, with severe hypertriglyceridemia secondary to biallelic LMF1 variants. In two of the three cases (patients 1 and 3), the presentation was acute pancreatitis secondary to plasma triglycerides well above 10 mmol/L. The other case (patient 2) was a sibling of one of the initial patients, who was asymptomatic but markedly hypertriglyceridemic. Next-generation sequencing revealed a homozygous splice-site variant in exon 6 of LMF1 in patients 1 and 2 (c.897G>A, p.Gln299=), and a homozygous missense variant in exon 2 of LMF1 in patient 3 (c.233T>C, p.Leu78Pro). The finding of two disease-causing variants in three patients from the same location raises the question of whether LMF1 may be a more prevalent cause of severe hypertriglyceridemia among Latin-American patients.

Impact of hemagglutination activity and M2e immunity on conferring protection against influenza viruses.

To improve cross-protection of influenza vaccination, we tested conjugation of conserved M2e epitopes to the surface of inactivated influenza virus (iPR8-M2e*). Treatment of virus with chemical cross-linker led to diminished hemagglutination activity and failure to induce hemagglutination inhibiting antibodies. Conjugated iPR8-M2e* vaccine was less protective against homologous and heterosubtypic viruses, despite the induction of virus-specific binding IgG antibodies. In alternative approaches to enhance cross-protection, we developed a genetically linked chimeric protein (M2e-B stalk) vaccine with M2e of influenza A and hemagglutinin (HA) stalk of influenza B virus. Vaccination of mice with inactivated influenza A virus supplemented with M2e-B stalk effectively induced hemagglutination inhibiting antibodies, humoral and cellular M2e immune responses, and enhanced heterosubtypic protection. This study demonstrates the importance of HA functional integrity in influenza vaccine efficacy and that supplementation of influenza vaccines with M2e-B stalk protein could be a feasible strategy of improving cross-protection against influenza viruses.

Acute exposure to environmentally relevant concentrations of sucralose disrupts embryonic development and leads to an oxidative stress response in Danio rerio.

Sucralose (SUC) is the most consumed artificial sweetener worldwide, not metabolized by the human body, and barely eliminated from water in wastewater treatment plants. Although different studies have reported high concentrations of this sweetener in aquatic environments, limited to no information is known about the toxic effects this drug may produce over water organisms. Moreover, most of the current studies have used non-environmentally relevant concentrations of SUC for these effects. Herein, we aimed to evaluate the harmful effects that environmentally relevant concentrations of SUC may induce in the early life stages of Danio rerio. According to our results, SUC altered the embryonic development of D. rerio, producing several malformations that led to their death. The major malformations were scoliosis, pericardial edema, yolk deformation, and tail malformation. However, embryos also got craniofacial malformations, eye absence, fin absence, dwarfism, delay of the hatching process, and hypopigmentation. SUC also generated an oxidative stress response in the embryos characterized by an increase in the levels of lipid peroxidation, hydroperoxides, and carbonyl proteins. To overcome this oxidative stress response, we observed a significant increase in the levels of antioxidant enzymes superoxide dismutase and catalase. Moreover, a significant boost in the expression of antioxidant defense-related genes, Nuclear respiratory factor 1a (Nrf1a) and Nuclear respiratory factor 2a (Nrf2a), was also observed at all concentrations. Concerning apoptosis-related genes, we observed the expression of Caspase 3 (CASP3) and Caspase 9 (CASP9) was increased in a concentration-dependent manner. Overall, we conclude environmentally relevant concentrations of SUC are harmful to the early life stages of fish as they produce malformations, oxidative stress, and increased gene expression of apoptosis-related genes on embryos.