Detection of SARS-CoV-2 Delta Variant (B.1.617.2) in Domestic Dogs and Zoo Tigers in England and Jersey during 2021.

Reverse zoonotic transmission events of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described since the start of the pandemic, and the World Organisation for Animal Health (WOAH) designated the detection of SARS-CoV-2 in animals a reportable disease. Eighteen domestic and zoo animals in Great Britain and Jersey were tested by APHA for SARS-CoV-2 during 2020-2023. One domestic cat (Felis catus), three domestic dogs (Canis lupus familiaris), and three Amur tigers (Panthera tigris altaica) from a zoo were confirmed positive during 2020-2021 and reported to the WOAH. All seven positive animals were linked with known SARS-CoV-2 positive human contacts. Characterisation of the SARS-CoV-2 variants by genome sequencing indicated that the cat was infected with an early SARS-CoV-2 lineage. The three dogs and three tigers were infected with the SARS-CoV-2 Delta variant of concern (B.1.617.2). The role of non-human species in the onward transmission and emergence of new variants of SARS-CoV-2 remain poorly defined. Continued surveillance of SARS-CoV-2 in relevant domestic and captive animal species with high levels of human contact is important to monitor transmission at the human-animal interface and to assess their role as potential animal reservoirs.

Elevated angiotensin-converting enzyme 2 (ACE2) expression in cats with hypertrophic cardiomyopathy.

Angiotensin-converting enzyme 2 (ACE2) is an enzyme within the renin-angiotensin-aldosterone system that plays a role in regulating blood pressure. However, it is also a cellular receptor for infection with SARS coronaviruses. Although most cats develop subclinical or mild disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquired from human patients, a previous study has suggested hypertrophic cardiomyopathy (HCM) is a potential risk factor for the development of severe disease in the cat. Herein we investigate the ACE2 protein expression in the lung, heart, and kidney from a small subset of cats with (n = 10) and without HCM (n = 10) by immunohistochemistry. The abundance and intensity of ACE2 expression is slightly elevated in alveoli (p = 0.09; 0.07, respectively) and bronchioles (p = 0.095; 0.37, respectively). However, statistically elevated abundance and intensity of ACE-2 expression was only evident in the heart of cats with HCM (p = 0.032; p = 0.011, respectively). Further investigation did not demonstrate a statistical correlation between the ACE2 expression in the heart in relation to the heart weight to body weight ratio, and the ventricular wall ratio. Current findings suggest an overexpression of ACE2 in HCM cases but follow up study is warranted to understand the pathophysiological process.

Blood Biomarkers of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), either used in monotherapy or in combination with chemotherapy. While some patients achieve durable responses, some will not get benefit from this treatment. Early identification of non- responder patients could avoid unnecessary treatment, potentially serious immune-related adverse events and reduce treatment costs. PD-L1 expression using immunohistochemistry is the only approved biomarker for the selection of patients that can benefit from immunotherapy. However, application of PD-L1 as a biomarker of treatment efficacy shows many deficiencies probably due to the complexity of the tumor microenvironment and the technical limitations of the samples. Thus, there is an urgent need to find other biomarkers, ideally blood biomarkers to help us to identify different subgroups of patients in a minimal invasive way. In this review, we summarize the emerging blood-based markers that could help to predict the response to ICIs in NSCLC.

Gross pathology of high pathogenicity avian influenza virus H5N1 2021-2022 epizootic in naturally infected birds in the United Kingdom.

High pathogenicity avian influenza virus (HPAIV) clade 2.3.4.4b has re-emerged in the United Kingdom in 2021-2022 winter season, with over 90 cases of HPAIV detected among poultry and captive birds in England, Scotland, Wales, and Northern Ireland. Globally, HPAIV H5N1 has also had a wide geographical dispersion, causing outbreaks in Europe, North America, Asia, and Africa, impacting on socioeconomic and wildlife conservation. It is important to raise awareness of the gross pathological features of HPAIV and subsequently aid disease investigation through definition of pathological indicators following natural infection. In this study, we report on the gross pathology of HPAI H5N1 in poultry species (chicken, turkey, pheasant, guineafowl, duck, goose), and captive or wild birds (mute swan, tufted duck, jackdaw, peahen, white-tailed eagle) that tested positive between October 2021 and February 2022. Pancreatic and splenic necrosis were the common pathological findings in both Galliformes and Anseriformes. In addition to the more severe lesions documented in Galliformes, we also noted increased detection of pathological changes in a broader range of Anseriformes particularly in domestic ducks, in contrast to those reported in previous seasons with other H5Nx HPAIV subtypes. A continual effort to characterise the pathological impact of the disease is necessary to update on the presentation of HPAIV for both domestic/captive and wild birds whilst guiding early presumptive diagnosis.

A Review of Multisensor Data Fusion Solutions in Smart Manufacturing: Systems and Trends.

Manufacturing companies increasingly become "smarter" as a result of the Industry 4.0 revolution. Multiple sensors are used for industrial monitoring of machines and workers in order to detect events and consequently improve the manufacturing processes, lower the respective costs, and increase safety. Multisensor systems produce big amounts of heterogeneous data. Data fusion techniques address the issue of multimodality by combining data from different sources and improving the results of monitoring systems. The current paper presents a detailed review of state-of-the-art data fusion solutions, on data storage and indexing from various types of sensors, feature engineering, and multimodal data integration. The review aims to serve as a guide for the early stages of an analytic pipeline of manufacturing prognosis. The reviewed literature showed that in fusion and in preprocessing, the methods chosen to be applied in this sector are beyond the state-of-the-art. Existing weaknesses and gaps that lead to future research goals were also identified.

Prevalence of vitamin D deficiency and association with parathyroid hormone.

Objectives: We evaluated the prevalence of 25-hydroxyvitamin D (25-(OH)D) deficiency in our setting according to season, sex, and age. We also studied the association with parathyroid hormone (PTH) levels. Methods: The study population comprised all patients with requests for assessment of 25-(OH)D between January 1 and December 31, 2018, as registered in the database of the laboratory information system. Major exclusion criteria were pediatric samples (<18 years) and factors affecting 25-(OH)D and/or PTH levels (i.e., kidney injury, liver disease, PTH disorders). Results: Among 33,601 patients (24,028 women, 9,573 men), the prevalence of 25-(OH)D deficiency was 48%. Prevalence was greater in males than in females (53% vs. 46%). By age group, deficiency was more prevalent in quartile 1 (Q1, 74-87 years) and less prevalent in quartile 2 (Q2, 60-73 years). By season, deficiency was greater in spring (nonsignificant differences with respect to winter) and lower in summer. The association between 25-(OH)D and PTH was assessed in 9,368 persons. Linear regression analysis showed a weak association (coefficient - 0.303). Multiple logistic regression analysis revealed a significant association between 25-(OH)D deficiency and increased PTH (Odds ratio (OR), 1.63). Other risk factors for increased PTH include female sex (OR, 1.27), season (winter, OR 1.63, spring OR 1.16), and age (quartile 1, OR, 3). Conclusions: The prevalence of 25-(OH)D deficiency differed according to sex, age, and season of the year. Furthermore, elevation of PTH is mainly influenced by low 25-(OH)D, female sex, season, and age.

Sickle cell disease associated with thalassemia; description of a rare mutation.

Sickle cell disease (SCD) is a common hemoglobinopathy, secondary to alterations in the ß globin chain, resulting in an abnormal hemoglobin variant named as hemoglobin S. These disorders show a wide phenotypical spectrum, and the prevalence of these disorders has significantly changed over the time because of multiple factors such as migration. We report a case of a 17-year-old black male, born in Gambia, diagnosed with sickle cell disease, who presented an associated mutation only described in a Japanese family (Oshima et al., 1996).

Management and Outcomes of Bleeding Within 30 Days of Colonic Polypectomy in a Large, Real-Life, Multicenter Cohort Study.

BACKGROUND & AIMS: Management of delayed (within 30 days) postpolypectomy bleeding (DPPB) has not been standardized. Patients often undergo colonoscopies that do not provide any benefit. We aimed to identify factors associated with therapeutic intervention and active bleeding after DPPB. METHODS: We performed a retrospective study of 548 patients with bleeding within 30 days after an index polypectomy (DPPB; 71.9% underwent colonoscopy, 2.6% underwent primary angiographic embolization, and 25.5% were managed without intervention) at 6 tertiary centers in Spain, from January 2010 through September 2018. We collected demographic and medical data from patients. The primary outcomes were the need for therapeutic intervention and the presence of active bleeding during colonoscopy. RESULTS: A need for therapeutic intervention was associated independently with the use of antithrombotic agents, hemoglobin decrease greater than 2 g/dL, hemodynamic instability, and comorbidities (P < .05). The bleeding point during colonoscopy was identified in 344 patients; 74 of these patients (21.5%) had active bleeding. Active use of anticoagulants (odds ratio [OR], 2.6; 95% CI, 1.5-4.5), left-sided polyps (OR, 1.95; 95% CI, 1-3.8), prior use of electrocautery (OR, 2.6; 95% CI, 1.1-6.1), and pedunculated polyp morphology (OR, 1.8, 95% CI, 1-3.2) significantly increased the risk of encountering active bleeding. We developed a visual nomogram to estimate the risk of active bleeding. Overall, 43% of the cohort did not require any hemostatic therapy. Rebleeding (<6%) and transfusion requirements were low in those managed without intervention. CONCLUSIONS: In a study of patients with DPPB, we found that almost half do not warrant any therapeutic intervention. Colonoscopy often is overused for patients with DPPB. We identified independent risk factors for active bleeding that might be used to identify patients most likely to benefit from colonoscopy.

Piezo2 Mediates Low-Threshold Mechanically Evoked Pain in the Cornea.

Mammalian Piezo2 channels are essential for transduction of innocuous mechanical forces by proprioceptors and cutaneous touch receptors. In contrast, mechanical responses of somatosensory nociceptor neurons evoking pain, remain intact or are only partially reduced in Piezo2-deficient mice. In the eye cornea, comparatively low mechanical forces are detected by polymodal and pure mechanosensory trigeminal ganglion neurons. Their activation always evokes ocular discomfort or pain and protective reflexes, thus being a unique model to study mechanotransduction mechanisms in this particular class of nociceptive neurons. Cultured male and female mouse mechano- and polymodal nociceptor corneal neurons display rapidly, intermediately and slowly adapting mechanically activated currents. Immunostaining of the somas and peripheral axons of corneal neurons responding only to mechanical force (pure mechano-nociceptor) or also exhibiting TRPV1 (transient receptor potential cation channel subfamily V member 1) immunoreactivity (polymodal nociceptor) revealed that they express Piezo2. In sensory-specific Piezo2-deficient mice, the distribution of corneal neurons displaying the three types of mechanically evoked currents is similar to the wild type; however, the proportions of rapidly adapting neurons, and of intermediately and slowly adapting neurons were significantly reduced. Recordings of mechano- and polymodal-nociceptor nerve terminals in the corneal surface of Piezo2 conditional knock-out mice revealed a reduced number of mechano-sensitive terminals and lower frequency of nerve terminal impulse discharges under mechanical stimulation. Eye blinks evoked by von Frey filaments applied on the cornea were lower in Piezo2-deficient mice compared with wild type. Together, our results provide direct evidence that Piezo2 channels support mechanically activated currents of different kinetics in corneal trigeminal neurons and contributes to transduction of mechanical forces by corneal nociceptors.SIGNIFICANCE STATEMENT The cornea is a richly innervated and highly sensitive tissue. Low-threshold mechanical forces activate corneal receptors evoking discomfort or pain. To examine the contribution of Piezo2, a low-threshold mechanically activated channel, to acute ocular pain, we characterized the mechanosensitivity of corneal sensory neurons. By using Piezo2 conditional knock-out mice, we show that Piezo2 channels, present in the cell body and terminals of corneal neurons, are directly involved in acute corneal mechano-nociception. Inhibition of Piezo2 for systemic pain treatment is hindered because of its essential role for mechano-transduction processes in multiple body organs. Still, topical modulation of Piezo2 in the cornea may be useful to selectively relief unpleasant sensations and pain associated with mechanical irritation accompanying many ocular surface disorders.

Clinical Activity of Afatinib in Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Spanish Retrospective Multicenter Study.

INTRODUCTION: Uncommon epidermal growth factor receptor (EGFR) mutations (u-EGFRm) are a heterogeneous group of molecular alterations and have also been reported as comutations with other EGFR mutations (complex mutations) in non-small-cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, and we examined its efficacy in Spanish clinical practice. PATIENTS AND METHODS: Data of 67 patients with advanced NSCLC with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. u-EGFRm were analyzed as complex mutations (group A), EGFR exon 20 insertions (ins20; group B), or single mutations (group C). Efficacy was evaluated in terms of overall survival (OS) and tumor response. RESULTS: Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q. No differences in clinical characteristics were found between groups A (n = 20), B (n = 23), and C (n = 24). Afatinib was administered as first-line therapy in 80% of patients. Median time of receipt of therapy was 4.2 months (range, 2.0-12.9 months). Median OS for the entire cohort was 19.9 months (95% confidence interval, 9.7, 30.1). Hazard ratios for OS were 0.26 (95% confidence interval, 0.10, 0.71; P = .008) and 0.40 (95% confidence interval, 0.17, 0.95; P = .037) for groups A and C compared to B, respectively. Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P < .001 and .008, respectively). CONCLUSION: In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.

Efficacy of immunotherapy in sarcomatoid lung cancer, a case report and literature review.

Sarcomatoid carcinoma is a subtype of non-small cell lung cancer (NSCLC) characterized by mesenchymal - epithelial transition component and awful prognosis. In this report, based on a case of stage IV lung sarcomatoid carcinoma with an extraordinary evolution and survival over 4 years, we address unresolved questions about the treatment of this cancer. We also make a literature review about the key factors that characterize this histology and that should be considered when treating those patients. Sarcomatoid carcinoma presents with mutations as KRAS, EGFR, ALK or MET in up to 70% of cases, and an important expression of PD-L1 (also called B7-H1), which can influence treatment of those patients with new drugs as immune checkpoint inhibitors. Immunotherapy has changed the horizon of patients with stage IV lung cancers without driver mutations, as their survival has improved extraordinary. Moreover, radical treatments are being considered in long survivors with oligometastatic disease. In this report, we review targeted and radical therapy, treatment duration and the mechanisms responsible of disease evolution of sarcomatoid tumors.

Niñez y adolescencia en el contexto de la migración: principios, avances y desafíos en la protección de sus derechos en América Latina y el Caribe / Childhood and adolescence in the context of migration: principles, advancements, and challenges for protecting their rights in Latin America and the Caribbean

El presente artículo busca dar un panorama sobre la situación de la niñez y la adolescencia en América Latina y el Caribe; específicamente, sobre los avances y desafíos actuales que se presentan a los países de la región en materia de los derechos humanos de los niños, niñas y adolescentes (NNA) en el contexto de la migración. Con tal fin, se hace una descripción general sobre el tema con base en algunos principios generales que se derivan de la Convención sobre los Derechos del Niño, a partir de los cuales pueden construirse ciertos estándares concretos aplicables sobre NNA migrantes e hijos/as de migrantes. Luego, se presentan sucintamente dos casos puntuales que dan cuenta precisamente sobre la variedad de contextos, oportunidades y retos sobre la temática en la región: Argentina y México.(AU)

The present article strives to give a panorama of the situation of youth in Latin America and the Caribbean, especially regarding the current advancements and challenges facing the region's countries on the issue of the human rights of children and adolescents (NNA) in the context of immigration. With such an end, the article forms a general description based upon certain broad principles derived from the Convention of the Rights of the Child, upon which can be constructed some concrete standards applicable to NNA migrants and their children. We present two timely cases which succinctly and precisely cover the variety of contexts, opportunities, and challenges within the region: Argentina and Mexico.(AU)

2009-2010 seasonal and pandemic A (H1N1) influenza vaccination among healthcare workers.

Influenza vaccination recommendations are traditionally met with low compliance by healthcare workers (HCWs). The aim of this study is to analyze influenza vaccination among HCWs following a vaccination strategy characterized by an increased effort to maximize the hospital vaccination rate. For this, 2009-2010 seasonal and pandemic influenza vaccination rates among 2739 HCWs at a tertiary university hospital were evaluated. The seasonal influenza vaccination rate was 26.7% (48.3% increase vs. 2008-2009, p=0.0000), and 14.8% in the case of pandemic influenza. HCWs with direct patient contact showed similar seasonal (25.7%) and pandemic (15.4%) influenza vaccination rates compared to the overall rates. Physician vaccination displayed the highest rate, showing significant differences vs. total rate (38.3%, p=0.0007 for seasonal, and 32.2%, p=0.0000 for pandemic influenza). The areas in which the vaccination strategy was most active reflected a significant increase (32.6%, p=0.0056 for seasonal, and 25.2%, p=0.0000 for pandemic influenza). It therefore appears that more active campaigns might increase influenza vaccination among HCWs.

Cerebrovascular reactivity over time-course - from major depressive episode to remission.

INTRODUCTION: Depression is a prospective risk factor for stroke. Little is known, however, about the pathophysiologic links leading to this association. Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism to provide constant cerebral blood flow. In the absence of major arterial stenosis, an impaired CVR has been associated with a higher risk of stroke. We hypothesized that CVR might be continuously reduced in patients with major depression even after successful remission thus contributing to the association between depression and stroke. MATERIALS AND METHODS: We investigated CVR in a group of patients (N=29) in the acute episode of depressive illness and after 21months under euthymic condition. A healthy control group (N=33) was investigated at comparable time intervals. All patients and controls were otherwise healthy. CVR was investigated by calculating the increase in cerebral blood flow velocity after stimulation with acetazolamide. Blood flow velocities were measured by transcranial doppler ultrasound. RESULTS: A group of acutely depressed patients presented a significantly reduced CVR compared to controls. On follow-up 21months later after treatment and remission, CVR in the patient group had significantly improved, whereas CVR in the control group remained unchanged. Confounding factors had no significant influence. DISCUSSION: CVR is impaired during major depression. Since CVR seems to improve after treatment of depression, the contribution to an increased stroke risk among depressive patients may be true for a subgroup only and needs to be further investigated.

Comparison of midlatency auditory sensory gating at short and long interstimulus intervals.

RATIONALE: Suppression of P50, N100 and P200 auditory evoked responses in a dual-click procedure is considered an index for the multistage sensory gating process. Whereas most studies use a protocol with long interstimulus intervals of 8-12 s between the stimuli pairs, there is also evidence that sensory gating occurs at much lower intervals. The aim of the study was to investigate whether a simple modified dual-click protocol with short interstimulus intervals elicts similar sensory gating ratios compared to the classic protocol. METHODS: P50, N100 and P200 amplitudes and sensory gating ratios were measured in 23 healthy subjects with 2 different dual-click protocols in 1 session: (1) a simple oddball modified with short interstimulus intervals of about 2.8 s (ISI2), and (2), the classic used with long intervals of about 8 s (ISI8). RESULTS: The amplitudes of the P50, N100 and P200 responses were mostly comparable and correlated between both protocols. Mean sensory gating ratios (ISI8/ISI2) were as follows: P50, 35.4/36.4%; N40P50, 36.1/39.9%; N100, 44.4/48.4%; P200, 46.8/43.3%; N100P200, 45.3/41.8%; all differences between protocols, p > 0.1. P50 ratio scores did not show a sufficient correlation between protocols [intraclass correlation coefficient (ICC) P50, 0.13; N40P50, 0.0] compared to N100 (ICC, 0.79), P200 (ICC, 0.6) and N100P200 (ICC, 0.61). CONCLUSION: Our results contradict the assumption that long interstimulus intervals of about 8 s are absolutely necessary to elicit a marked sensory gating phenomenon for P50, N100 and P200 auditory responses (at least when using a protocol with a simple attention task). However, because only healthy subjects were investigated, no prediction can be made for psychiatric patients, in whom neuronal processing may be different.

Child health in rural Colombia: determinants and policy interventions.

We study the determinants of child anthropometrics on a sample of poor Colombian children living in small municipalities. We focus on the influence of household consumption, and public infrastructure, taking into account the endogeneity of household consumption using two different sets of instruments: household assets and municipality average wage. We find that both household consumption and public infrastructure are important determinants of child health. We have also found that the coverage of the piped water network positively influenced child health if the parents have some education.