Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2.

BACKGROUND: Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. METHODS: Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo- and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cellular reactivity, we used an IFN-γ Elispot, IFN-γ/IL Flurospot, and intracellular cytokine staining. FINDINGS: Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses. INTERPRETATION: These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens. FUNDING: The study was funded by the German Centre for Infection Research (DZIF), the European Union's "Horizon 2020 Research and Innovation Programme" under grant agreement No. 101037867 (VACCELERATE), the "Bayerisches Staatsministerium für Wissenschaft und Kunst" for the CoVaKo-2021 and the For-COVID projects and the Helmholtz Association via the collaborative research program "CoViPa". Further support was obtained from the Federal Ministry of Education and Science (BMBF) through the "Netzwerk Universitätsmedizin", project "B-Fast" and "Cov-Immune". KS is supported by the German Federal Ministry of Education and Research (BMBF, 01KI2013) and the Else Kröner-Stiftung (2020_EKEA.127).

Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back.

Over the past decades, the relationship between the immune system and metabolism has become a major research focus. In this arena of immunometabolism the capacity of adipose tissue to secrete immunomodulatory molecules, including adipokines, within the underlying low-grade inflammation during obesity brought attention to the impact obesity has on the immune system. Adipokines, such as leptin and adiponectin, influence T cell differentiation into different T helper subsets and their activation during immune responses. Furthermore, within the cellular milieu of adipose tissue nutrient availability regulates differentiation and activation of T cells and changes in cellular metabolic pathways. Upon activation, T cells shift from oxidative phosphorylation to oxidative glycolysis, while the differential signaling of the kinase mammalian target of rapamycin (mTOR) and the nuclear receptor PPARγ, amongst others, drive the subsequent T cell differentiation. While the mechanisms leading to a shift from the typical type 2-dominated milieu in lean people to a Th1-biased pro-inflammatory environment during obesity are the subject of extensive research, insights on its impact on peripheral Th2-dominated immune responses become more evident. In this review, we will summarize recent findings of how Th2 cells are metabolically regulated during obesity and malnutrition, and how these states affect local and systemic Th2-biased immune responses.

Isochronous mass spectrometry in an electrostatic storage ring.

For sensitive studies of molecular ions in electrostatic storage rings, the exact knowledge of the isobaric composition of stored beams from a variety of ion sources is essential. Conventional mass-filtering techniques are often inefficient to resolve the beam components. Here, we report the first isochronous mass spectrometry in an electrostatic storage ring, which offers a high mass resolution of Δm/m < 1 × 10-5 even for heavy molecular species with m > 100 u and uncooled ion beams. Mass contaminations can be resolved and identified at relative fractions down to 0.02%.

Innate PD-L1 limits T cell-mediated adipose tissue inflammation and ameliorates diet-induced obesity.

Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy.

Quantum-state-selective electron recombination studies suggest enhanced abundance of primordial HeH.

The epoch of first star formation in the early Universe was dominated by simple atomic and molecular species consisting mainly of two elements: hydrogen and helium. Gaining insight into this constitutive era requires a thorough understanding of molecular reactivity under primordial conditions. We used a cryogenic ion storage ring combined with a merged electron beam to measure state-specific rate coefficients of dissociative recombination, a process by which electrons destroy molecular ions. We found a pronounced decrease of the electron recombination rates for the lowest rotational states of the helium hydride ion (HeH+), compared with previous measurements at room temperature. The reduced destruction of cold HeH+ translates into an enhanced abundance of this primordial molecule at redshifts of first star and galaxy formation.

Decision making in patients with natural myringostapediopexy: A study of the contralateral ear.

Naturally occurring myringostapediopexy frequently results in minimal hearing loss and is asymptomatic. Management decisions in such ears, however, often hinge on an appraisal of evolution toward cholesteatoma. The study of the contralateral ear has been used by our research team to infer the progression of chronic otitis media. This cross-sectional, comparative study describes the clinical findings of the contralateral ear in a series of patients with myringostapediopexy. This study included a historical and current sample of 46 patients divided into a pediatric (≤18 years) and an adult group. Patient distribution according to sex was similar (52.2% male), and 56.5% were adults. Mean conductive hearing loss ranged from 14.1 to 21.2 dB in ears with myringostapediopexy and from 16.0 to 26.6 dB in the contralateral ears according to the frequency assessed. The contralateral ear was normal in only 19.6% of the cases of myringostapediopexy. Central tympanic membrane perforation was found in 6.5% of the cases; perforation-retraction, in 17.4%; moderate or severe retraction, in 28.3%; and cholesteatoma, in 28.3%. The prevalence of cholesteatoma in the contralateral ear in the pediatric and adult groups was not significantly different (p = 0.5; χ(2) test). The presence of significant abnormalities, particularly cholesteatoma, in the contralateral ears suggests a probable unfavorable progression in cases of myringostapediopexy and may influence management decisions.

Myringostapediopexy: is it a natural type III tympanoplasty?

INTRODUCTION: Natural myringostapediopexy is an infrequent abnormality, and studies about resulting hearing loss are scarce. In several cases, natural myringostapediopexy may function as a Type III tympanoplasty. OBJECTIVE: This study evaluated conductive hearing loss in myringostapediopexy. MATERIALS AND METHODS: This cross-sectional comparative study included a historical and current sample of 46 patients, one with bilateral myringostapediopexy, at a total of 47 ears. All underwent pure tone and speech audiometry and were divided according to age into a pediatric (younger than 18 yr) and an adult group. The Statistical Package for Social Science (SPSS) 10.0 was used for statistical analysis, and the level of significance was set at p lower than 0.05. RESULTS: Patient distribution according to sex was similar (53.2% male), and 57.4% were adults. Mean conductive hearing loss in ears with myringostapediopexy ranged from 14.13 to 21.28 dB according to the frequency assessed. Pure tone average was 18.46 dB. A conductive hearing loss equal to or lower than 25 dB at all frequencies was found in 53% of the patients. The 2,000 and 3,000 Hz frequencies had the greatest prevalence of clinically nonsignificant conductive hearing loss (87% and 91%). Sensorineural hearing loss was found in 14 patients (30%), all adults, and 43% of the cases were mild. The comparison according to age did not reveal any significant differences in conductive hearing loss at any of the frequencies. CONCLUSION: Most patients with natural myringostapediopexy included in the study had clinically irrelevant conductive hearing loss. There were no differences in conduction loss between children and adults. The reconstruction of the ossicular chain and tympanoplasty, for purely functional reasons, are not justified in these cases, particularly not for patients with mixed hearing loss.

Implementação do programa de triagem auditiva neonatal universal em hospital universitário de município da região Sul do Brasil: resultados preliminares / Implementation of a program of universal newborn hearing screening in a university hospital in a city in south Brazil: preliminary results

Introdução: A triagem auditiva neonatal (TAN) possibilita identificar precocemente a deficiência auditiva nos primeiros meses de vida, o que permite diagnóstico e intervenção necessários nessas crianças. O objetivo desse estudo foi traçar o perfil epidemiológico de recém-nascidos submetidos à TAN em um hospital universitário. Métodos: Estudo transversal realizado em no período de Outubro de 2009 a Setembro de 2010. O teste de triagem auditiva neonatal foi efetuado em todos os recém-nascidos na maternidade da instituição. Resultados: O total de pacientes avaliados foi de 2..165 crianças, destas, 17% dos recém-nascidos falharam no primeiro teste de emissões otoacústicas; 4% falharam no reteste e destas 0,2% apresentaram deficiência na audição. Um recém-nascido recebeu prótese. Conclusões: Os dados obtidos nesse estudo estão condizentes com a literatura atual. Firmar programas como a TAN em um serviço universitário torna-se essencial para promover melhora no manejo das crianças afetadas por perda auditiva.

Introduction: The newborn hearing screening (NHS) provides early identification of hearing loss in the first months of life, allowing diagnosis and intervention needed in these children. The aim of this study was to determine the epidemiological profile of infants submitted to NHS in a university hospital. Methods: Cross-sectional study conducted from Oct 2009 to Sept 2010. The newborn hearing screening test was performed on all newborns in the maternity ward of the institution. Results: The total number of patients was 2,165 infants; of these, 17% failed the first test of otoacoustic emissions, 4% failed in the re-test, and of these 0.2% presented hearing impairment. One newborn received a prosthesis. Conclusions: The data obtained in this study are consistent with the current literature. Establishing programs like the NHS at a university service becomes essential to promote improvement in the management of children affected by hearing loss.

Latex biomembrane: a new method to coat the open cavity in tympanomastoidectomies.

UNLABELLED: The new cavity created after an open cavity tympanomastoidectomy (OCTM) is filled with an antibiotic impregnated cotton pack (cotton tape, umbilical tape, gauze). The removal of this pack usually causes some bleeding and discomfort for the patient. We propose the use of a latex biomembrane to cover the cavity, which will act as an interface between the raw bone surface and the packing. STUDY DESIGN: clinical prospective. AIM: To study the performance of the latex biomembrane as an interface between the raw bone surface and the pack, and to analyze its role in cavity epithelization. MATERIAL AND METHODS: 64 ears of patients submitted to OCTM were studied. The biomembrane was used in the packing of 54 ears and in the 10 remaining ears the regular cotton tape packing was used. RESULTS: In the majority of the cases where the biomembrane was used the packing was removed much easier with no bleeding or pain for the patient and also showed an earlier cavity epithelization. CONCLUSION: The use of the latex biomembrane has proven to be an effective method to cover the mastoid cavity facilitating epithelization and removal of mastoid cavity packing.

Biomembrana de látex: novo método para o revestimento da cavidade aberta nas timpanomastoidectomia / Latex biomembrane: a new method to coat the open cavity in tympanomastoidectomies

As neocavidades pós-timpanomastoidectomias de cavidade aberta (TMCA) são normalmente preenchidas por cadarço ou fita cardíaca untados com pomada antibiótica. A remoção deste tampão usualmente causa sangramento e desconforto para o paciente. Propomos para tanto a utilização de uma biomembrana de látex natural para forrar a neocavidade, servindo como uma interface entre o osso cruento e o material de tamponamento. FORMA DE ESTUDO: Clínico prospectivo. OBJETIVOS: Estudar o desempenho da biomembrana como uma interface entre o osso cruento e o material de tamponamento e analisar seu papel na epitelização da neocavidade. MATERIAL E MÉTODO: Foram analisadas 64 orelhas de pacientes submetidos à TMCA e meatoplastia. A biomembrana foi utilizada em 54 das orelhas operadas, sendo que nas outras 10 orelhas o tamponamento da cavidade foi realizado somente com fita cardíaca. RESULTADOS: Na maioria das 54 orelhas onde a biomembrana foi utilizada observou-se maior facilidade na remoção do curativo tampão (sem sangramento ou desconforto para o paciente), menor demanda de tempo para sua retirada, além da epitelização mais precoce da neocavidade. CONCLUSÃO: A utilização da biomembrana de látex revelou-se método eficaz no revestimento da neocavidade, facilitando a remoção do tampão e a epitelização da neocavidade.

The new cavity created after an open cavity tympanomastoidectomy (OCTM) is filled with an antibiotic impregnated cotton pack (cotton tape, umbilical tape, gauze). The removal of this pack usually causes some bleeding and discomfort for the patient. We propose the use of a latex biomembrane to cover the cavity, which will act as an interface between the raw bone surface and the packing. STUDY DESIGN: clinical prospective. AIM: To study the performance of the latex biomembrane as an interface between the raw bone surface and the pack, and to analyze its role in cavity epithelization. MATERIAL AND METHODS: 64 ears of patients submitted to OCTM were studied. The biomembrane was used in the packing of 54 ears and in the 10 remaining ears the regular cotton tape packing was used. RESULTS: In the majority of the cases where the biomembrane was used the packing was removed much easier with no bleeding or pain for the patient and also showed an earlier cavity epithelization. CONCLUSION: The use of the latex biomembrane has proven to be an effective method to cover the mastoid cavity facilitating epithelization and removal of mastoid cavity packing.

O BERA como instrumento de avaliação funcional do tronco cerebral em cirurgias com hipotermia profunda e parada circulatória total / The ABR as a tool in the evaluation of brainstem function in surgeries with deep hypothermia and total cardiac arrest

OBJETIVO: Monitoramento do tronco cerebral através da análise dos traçados do BERA em cirurgia cardíaca com hipotermia profunda e parada circulatória total (PCT), registrando a recuperaçäo funcional (eletrofisiológica) do tronco cerebral. FORMA DE ESTUDO: Coorte Longitudinal. MATERIAL E MÉTODO: Foram estudados o comportamento do traçado do BERA de 8 pacientes submetidos a cirurgia cardíaca com hipotermia profunda e PCT para correçäo de aneurisma de aorta torácica. Etapas: resfriamento corporal até 18ºC C; PCT por até 60 minutos; reaquecimento. Registros do BERA: 35ºC, 32ºC, 26ºC, 18ºC, 27ºC, 35ºC. RESULTADOS: Os traçados iniciais (35ºC) se apresentavam normais. Aos 26ºC há o desaparecimento de todas as ondas. Aos 18ºC o traçado do BERA mostrava um padräo isoelétrico. Aos 27ºC, recuperaçäo das ondas I, III e V. A partir de 35ºC as latências das ondas retornam ao normal. CONCLUSÄO: O BERA constitui-se em competente instrumento de monitoramento da integridade funcional do tronco cerebral em cirurgia cardíaca com hipotermia profunda e PCT. As ondas desaparecem no período de resfriamento corporal, atingem um padräo isoelétrico a 18ºC, e reaparecem durante o reaquecimento. No final do procedimento, os médicos anestesistas näo dispöem de exame clínico fidedigno para acessar a integridade funcional do tronco cerebral, devido ao uso de drogas depressoras do SNC. O reaparecimento das ondas do BERA é o parâmetro proposto para este fim. A manutençäo do padräo isoelétrico após o reaquecimento corporal sugere grave comprometimento funcional do tronco cerebral

Estudo da orelha contralateral na otite média crônica: "Efeito Orloff" / Contralateral ear in chronic otitis media: \"Orloff Effect\"

Introduçäo: A otite média crônica (OMC) representa entidade de alta prevalência e distribuiçäo mundial. Apesar da grande quantidade de estudos publicados a respeito, ainda näo há, na literatura pertinente, consenso sobre a patogênese da OMC. Uma das hipóteses é a do continuum, que apresenta a otite média crônica como uma série de eventos contínuos, onde insultos iniciais desencadeiam uma cascata de alteraçöes. Partindo entäo da idéia de continuum, pesquisamos a orelha contralateral (OCL) de indivíduos com diagnóstico de OMC, descrevendo as alteraçöes encontradas. Forma de estudo: Clínico prospectivo randomizado. Material e Métodos: Foram selecionados 108 pacientes com diagnóstico de OMC näo-colesteatomatosa (OMC NC) ou colesteatomatosa (OMC C) acompanhados no ambulatório do Grupo de Pesquisa em Patologia da Orelha Média do Hospital de Clínicas de Porto Alegre. Nestes, foi realizada otoendoscopia com fibra óptica bilateral. A orelha mais estável foi considerada contralateral (OCL), sendo classificada como normal ou alterada (e as alteraçöes descritas). Resultados: Dentre os pacientes avaliados, 59,2 por cento portavam OMC NC e 40,8 por cento OMC C. 46,3 por cento de todos os pacientes apresentaram alteraçöes significativas na OCL. Dos pacientes com OMC C, 57 por cento apresentavam alteraçäo na OCL, sendo que 39 por cento dos pacientes com OMC NC tinham OCL alterada. A alteraçäo mais freqüentemente encontrada foi retraçäo de MT, em ambos os grupos. Conclusöes: Os dados encontrados sugerem que pacientes que apresentam OMC tem maior probabilidade de apresentarem patologia na OCL, o que corrobora a idéia que a OMC se trata de um evento constitucional e näo isolado da orelha média

Hipogonadismo hipogonadotrófico e anosmia: síndrome de Kallmann / Hypogonadotropic hypogonadism and anosmia: KallmannÆs syndrome

A síndrome de Kallmann caracteriza-se pela associação de hipogonadismo hipogonadotrófico à anosmia ou hiposmia. É causada por um defeito na migração dos neurônios que produzem o GnRH e dos neurônios que formam os nervos olfatórios. A doença afeta somente a secreção de gonadotrofina, sendo que todos os outros hormônios hipofisários são secretados normalmente. Neste trabalho são relatados dois casos de síndrome de Kallmann e apresentada revisão da literatura.

Contracepçäo hormonal contendo apenas progesterona / Hormonal contraception only with progesterone

A contracepçäo pode ser alcançada utilizando-se métodos hormonais ou näo. Os métodos hormonais podem ser combinados (estrógenos + progesterona) ou só conter progesterona. Iremos discutir neste artigo apenas aqueles à base de progesterona, incluindo novas opçöes como a pílula do dia seguinte e os endoceptivos. Os contraceptivos à base de progesterona säo administrados sob diferentes formas: via oral, intradérmica, injetável e intra-uterina. Todos estes métodos tem ótima eficácia, säo bem tolerados e têm menos contra-indicaçöes do que os métodos hormonais combinados. Seu efeito adverso mais freqüente é a irregularidade menstrual

Contracepção hormonal contendo apenas progesterona / Hormonal Contraception contend only progesterone

A contracepção pode ser alcançada utilizando-se métodos hormonais ou não. Os métodos hormonais podem ser combinados (estrógenos + progesterona) ou só conter progesterona. Iremos discutir neste artigo apenas aqueles à base de progesterona, incluindo novas opções como a pílula do dia seguinte e os endoceptivos. Os contraceptivos à base de progesterona são administrados sob diferentes formas: via oral, intradérmica, injetável e intra-uterina. Todos estes métodos tem ótima eficácia, são bem tolerados e têm menos contra-indicações do que os métodos hormonais combinados. Seu efeito adverso mais freqüente é a irregularidade menstrual(AU)

Contracepþõo hormonal contendo apenas progesterona / Hormonal contraception only with progesterone

A contracepþõo pode ser alcanþada utilizando-se métodos hormonais ou nõo. Os métodos hormonais podem ser combinados (estrógenos + progesterona) ou só conter progesterona. Iremos discutir neste artigo apenas aqueles O base de progesterona, incluindo novas opþ÷es como a pílula do dia seguinte e os endoceptivos. Os contraceptivos O base de progesterona sõo administrados sob diferentes formas: via oral, intradérmica, injetável e intra-uterina. Todos estes métodos tem ótima eficácia, sõo bem tolerados e tÛm menos contra-indicaþ÷es do que os métodos hormonais combinados. Seu efeito adverso mais freq³ente é a irregularidade menstrual (AU)