A Computationally Optimized Broadly Reactive Antigen Subtype-Specific Influenza Vaccine Strategy Elicits Unique Potent Broadly Neutralizing Antibodies against Hemagglutinin.

Computationally optimized broadly reactive Ags (COBRA) targeting H1 elicit a broad cross-reactive and cross-neutralizing Ab response against multiple H1N1 viral strains. To assess B cell breadth, Mus musculus (BALB/c) Ab-secreting cells elicited by a candidate COBRA hemagglutinin (HA) (termed P1) were compared with Ab-secreting cells elicited by historical H1N1 vaccine strains. In addition, to evaluate the Ab response elicited by P1 HA at increased resolution, a panel of P1 HA-specific B cell hybridomas was generated following immunization of mice with COBRA P1 and the corresponding purified mAbs were characterized for Ag specificity and neutralization activity. Both head- and stem-directed mAbs were elicited by the P1 HA Ag, with some mAbs endowed with Ab-dependent cell-mediated cytotoxicity activity. P1 HA-elicited mAbs exhibited a wide breadth of HA recognition, ranging from narrowly reactive to broadly reactive mAbs. Interestingly, we identified a P1 HA-elicited mAb (1F8) exhibiting broad hemagglutination inhibition activity against both seasonal and pandemic H1N1 influenza strains. Furthermore, mAb 1F8 recognized an overlapping, but distinct, epitope compared with other narrowly hemagglutination inhibition-positive mAbs elicited by the P1 or wild-type HA Ags. Finally, P1 HA-elicited mAbs were encoded by distinct H chain variable and L chain variable gene segment rearrangements and possessed unique CDR3 sequences. Collectively, the functional characterization of P1 HA-elicited mAbs sheds further insights into the underlying mechanism(s) of expanded Ab breadth elicited by a COBRA HA-based immunogen and advances efforts toward design and implementation of a more broadly protective influenza vaccine.

Gut microbiota of elite female football players is not altered during an official international tournament.

The current study aimed to investigate if the gut microbiota composition of elite female football players changes during an official international tournament. The study was conducted throughout ten consecutive days, encompassing seven training sessions, and three official matches. The matches were separated by 48-72 h. Seventeen elite female football players from the Portuguese women's national football team participated in the study. Fecal samples were collected at two time points: at the beginning and end of the tournament. Fecal microbiota was analyzed by sequencing the 16S rRNA gene. Throughout the study, the duration and rating of perceived exertion (RPE) were recorded after training sessions and matches. The internal load was determined by the session RPE. The gut microbiota of players was predominantly composed of bacteria from the phyla Firmicutes (50% of relative abundance) and Bacteroidetes (20%); the genera Faecalibacterium (29%) and Collinsella (16%); the species Faecalibacterium prausnitzii (30%) and Collinsella aerofaciens (17%). Overall, no significant changes were observed between time points (p ≥ 0.05). Also, no relationship was found between any exercise parameter and the gut microbiota composition (p ≥ 0.05). These findings demonstrate that the physical and physiological demands of training and matches of an official international tournament did not change the gut microbiota composition of elite female football players. Furthermore, it supports that the gut microbiota of athletes appears resilient to the physical and physiological demands of training and match play.

Dietary supplements usage by elite female football players: an exploration of current practices.

The present study aimed to investigate the prevalence of dietary supplements usage (types, reasons for usage, sources of information, purchase venues) among elite female football players, using a self-administered questionnaire. The study participants (n = 103) were recruited through team physicians during an official international tournament. Overall, 82% reported using dietary supplements at least once during the last 12 months. The most common dietary supplements were vitamin D (52%), omega-3 fatty acids (49%), and protein (45%). Primary reasons for dietary supplement use were to stay healthy (66%), to accelerate recovery (58%), and to increase energy/reduce fatigue (54%). Supplement advice came mainly from medical doctors (46%), dietitians/nutritionists (43%), and coaches/fitness coaches (41%). Most dietary supplements were acquired from supplement stores (30%), a sponsor (26%), or drugstores/pharmacies (22%). Elite female football players are frequent dietary supplement users. Further research needs to explore the frequency, dose, and timing of these supplements.

Perspectives and practices of nutritionists on dietary supplements for elite soccer teams: a cross-sectional survey study.

Introduction and objectives: Dietary supplements are part of the nutritional strategies frequently applied in sports performance support. With growing research on this subject and high demand from athletes, nutritionists need to keep up to date with the latest evidence and utility of dietary supplements, particularly in real-world contexts. As information about the use of dietary supplements among elite soccer players is still scarce, this work aimed to know how nutritionists working with elite soccer teams perceive and use these substances in their daily practice. Methods: A questionnaire previously used to describe nutritionists' beliefs and attitudes regarding the use of dietary supplements in a clinical context was adapted for this study. The online questionnaire was addressed to nutritionists working with elite soccer teams from six European Leagues and Brazil, between November 2022 and February 2023. Results: Overall, the participants considered themselves well-trained (76.9%), knowledgeable (95.4%), and interested in dietary supplements (95.4%). The majority (70.8%) of the participants agreed or strongly agreed to recommend dietary supplements to soccer players. Personal usage of dietary supplements was associated with recommending supplements (p < 0.001), but no relationships were found with years of experience and academic level. Discussion: Nutritionists working with elite soccer players consider the use of dietary supplements for performance-enhancement purposes and not only to compensate for nutritional deficits, which might contribute to their higher interest, training and perceived knowledge about this topic. Participants recognize players' interest in dietary supplements, and are mindful of the safety and efficacy of these products. The present study suggests that nutritionists working with elite soccer teams are among the highest prescribers of dietary supplements, although personal usage is lower than that of nutritionists working in a clinical context.

Effects of dietary supplements on athletic performance in elite soccer players: a systematic review.

Dietary supplements are widely used among athletes, and soccer players are no exception. Nevertheless, evidence supporting the use of dietary supplements aiming to enhance performance in soccer is somewhat contradictory, scarce, or even nonexistent. Thus, the present study aimed to systematically review and synthesize the effects of dietary supplements on athletic performance (e.g. distance covered, sprinting, jump performance) in elite soccer players. Studies enrolling highly trained, elite, and world-class soccer players using dietary supplements were searched in MEDLINE/PubMed, Web of Science, Scopus, and EBSCO databases in June 2022. In total, 1043 studies were identified, and 18 met the eligibility criteria. The studies evaluated the impacts on athletic performance of several dietary supplements, including caffeine, creatine, protein, beverages with carbohydrates and electrolytes, tart cherry juice, nitrate-rich beetroot juice, sodium bicarbonate with minerals, yohimbine, and a proprietary nutraceutical blend. Caffeine supplementation in doses between 3 and 6 mg/kg of body mass may improve jump height and sprint ability, particularly in female players, but individual response to caffeine must be considered. Creatine may improve sprint, agility, and in female players, jump performance. Protein supplementation can improve sprint and jump performance between matches, especially if protein ingested from food is not up to recommendations. Beverages containing carbohydrates and electrolytes can be used as part of the strategies to achieve carbohydrate intake during training and match-days but used alone do not benefit athletic performance. Tart cherry juice might be useful for maintaining athletic performance after matches that produce higher force loss and exercise-induced muscle damage, although polyphenols from the diet might attenuate the effects of tart cherry supplementation. Nitrate-rich beetroot concentrate can attenuate performance decrease in the days following matches. Further investigation with sodium bicarbonate alone is necessary, as supplementation protocols with elite players included other substances. Finally, the available data does not support yohimbine supplementation or the use of Resurgex Plus® to improve athletic performance in elite soccer players. Still, more well-designed research with elite soccer players is needed to improve support and advice regarding the use of dietary supplements for athletic performance enhancement.

Incidental Diagnosis of Oligosymptomatic Bilateral Perirenal Erdheim-Chester Disease during Emergency Investigation for COVID-19 Infection.

Erdheim-Chester disease (ECD), a rare form of non-Langerhans histiocytosis, is a multisystem disorder. The case reported here refers to a 49-year-old man presenting at the emergency room with respiratory symptoms. While undergoing diagnostic tests for COVID-19 infection, tomography revealed asymptomatic bilateral perirenal tumors, while renal function remained unaltered. ECD was suggested as an incidental diagnosis and confirmed by core needle biopsy. This report provides a brief description of the clinical, laboratory, and imaging findings in this case of ECD. This diagnosis, albeit rare, should be taken into consideration in the context of incidental findings of abdominal tumors to ensure that treatment, when required, is instituted early.

Pleomorphic hyalinizing angiectatic tumor of the vulva: literature review based on a rare presentation.

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft tissues is a rare, non-metastatic tumor of unknown etiology and uncertain behavior, which may recur locally. There are few reports on this condition, and due to the rarity of the disease, its lineage has not yet been fully elucidated. The present study aims to report the case of an unusual entity observed for the first time in vulval topography. A female patient, 83 years old, presented with a tumor in the vulvar region that had evolved for approximately 4 months. Magnetic resonance imaging showed an expansive perineal formation of 8.5 × 3.5 cm, and a hemivulvectomy with a flap rotation was performed. The review of the slides revealed a mesenchymal lesion without significant atypia, which was richly vascularized. In the areas of interest, the immunohistochemical (IHC) study demonstrated positivity for CD34, estrogen, and progesterone receptors; it was negative for the other tested markers. Morphological findings associated with the IHC staining panel supported the diagnosis of PHAT. The main morphological features of PHAT are clusters of ectatic vessels of different sizes that show deposits of subendothelial and intraluminal fibrin. Fusiform and pleomorphic cells randomly arranged in leaves or long fascicles intermingle these vessels. It is essential to recognize this entity and consider it among the differential diagnoses of a mesenchymal lesion, given the wide variety of entities that comprise this group of lesions.

NUT carcinoma, an under-recognized malignancy: a clinicopathologic and molecular series of 6 cases showing a subset of patients with better prognosis and a rare ZNF532::NUTM1 fusion.

NUT carcinoma (NC) is a rare malignancy with aggressive clinical behavior, defined by rearrangements involving the NUTM1 gene locus. This entity is often under-recognized and its diagnosis may be challenging. In this study, we describe a subset of patients that, despite the molecularly proven diagnosis of NC, show improved outcomes. In addition, we describe one case with the novel ZNF532::NUTM1 fusion. All cases of NC diagnosed from 2013 to 2022 in our department were retrieved. FISH using dual color bring-together probes and next-generation sequencing assay were performed to characterize the fusions involving NUTM1. Among 6 patients identified, 5 were men with a median age of 35.6 years. Four patients had primary tumors in the head and neck region (2 ethmoid sinus, 1 parotid gland, and 1 lacrimal gland); 1 in the mediastinum, and another presented with a femoral bone tumor. In all cases, the initial diagnoses were not NC. The cases showed different morphological patterns, including monomorphic, rhabdoid, and pleomorphic appearances. One case showed a pseudopapillary pattern. By immunohistochemistry, all tumors showed squamous differentiation and ≥50% of neoplastic cells with nuclear positivity for NUT antibody. One case expressed WT1 (C-terminus) and other showed chromogranin positivity. Genetic study revealed a BRD4::NUTM1 fusion in all head and neck cases, BRD3::NUTM1 in mediastinum case, and ZNF532::NUTM1 fusion in the femur bone case. They were treated with surgical resection plus chemotherapy and radiotherapy. The median overall survival was 23.11 months (1.6-83.3 months) and the median disease-free survival was 14.86 months (0-54.4 months). The patients with longer overall survival were one with a lacrimal gland primary (83.3 months) and other with a parotid lesion (31.9 months). Both patients were primarily treated with complete surgical resection. Anatomic location may be directly related to the overall survival in NC cases. Resectability of the lesion is also an important factor related to survival. Pathologists should include NC in the differential diagnosis of any poorly differentiated and undifferentiated monomorphic malignancy, regardless of its anatomic location.

Functional antibody-dependent cell mediated cytotoxicity (ADCC) responses to vaccine and circulating influenza strains following vaccination.

Novel cell-based assays were developed to assess antibody-dependence cellular cytotoxicity (ADCC) antibodies against both vaccine and a representative circulation strain HA and NA proteins for the 2014-15 influenza season. The four assays using target cells stably expressing one of the four proteins worked well. In pre- and post-vaccine sera from 70 participants in a pre-season vaccine trial, we found ADCC antibodies and a rise in ADCC antibody titer against target cells expressing the 4 proteins but a much higher titer for the vaccine than the circulating HA in both pre-and post-vaccine sera. These differences in HA ADCC antibodies were not reflected in differences in HA binding antibodies. Our observations suggested that relatively minor changes on the subtype HA can result in large differences in ADCC activity.

Ocular findings in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome.

OBJECTIVE: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare disorder. This study investigated the types of ocular signs and symptoms in patients with POEMS and any systemic factors that may be associated with development of such ocular findings. DESIGN: Case series from tertiary referral center. PARTICIPANTS: A total of 33 patients with POEMS syndrome underwent at least 1 ophthalmologic examination and were included in the study. METHODS: A 10-year retrospective chart review of patients diagnosed with POEMS syndrome was performed. MAIN OUTCOME MEASURES: Visual symptoms, visual acuity, presence of optic disc edema (ODE), and levels of systemic factors (including plasma vascular endothelial growth factor [VEGF], plasma interlukin-6 [IL-6], and raised intracranial pressure) and their relationship to ODE. RESULTS: Five of the patients (15%) reported diplopia, 15 patients (45%) had blurred vision, and 3 patients (9%) had ocular pain. The most common ocular finding was bilateral ODE in 17 patients (52%). Of the patients with ODE, 5 (29%) were asymptomatic at the first ocular examination. Among patients with ODE, there was a significant difference (P = 0.03) between the mean plasma VEGF level at the time of diagnosis of the ODE compared with when the ODE resolved. There was no difference in plasma IL-6 levels between people with and without ODE. Patients with ODE had a higher mean lumbar puncture opening pressure (276±14 mm H(2)O; normal range, 100-250 mm H(2)0) than patients without ODE, although the difference was not statistically significant (P = 0.08). CONCLUSIONS: Optic disc edema is a common finding in patients with POEMS. Because patients can be asymptomatic, eye examinations should be performed in all patients with POEMS. There may be an association between elevated VEGF and intracranial pressure and ODE; further studies are required.

Impaired memory B-cell recall responses in the elderly following recurrent influenza vaccination.

Influenza is a highly contagious viral respiratory disease that affects million of people worldwide each year. Annual vaccination is recommended by the World Health Organization with the goal of reducing influenza severity and limiting transmission through elicitation of antibodies targeting the hemagglutinin (HA) glycoprotein. The antibody response elicited by current seasonal influenza virus vaccines is predominantly strain-specific, but pre-existing influenza virus immunity can greatly impact the serological antibody response to vaccination. However, it remains unclear how B cell memory is shaped by recurrent annual vaccination over the course of multiple seasons, especially in high-risk elderly populations. Here, we systematically profiled the B cell response in young adult (18-34 year old) and elderly (65+ year old) vaccine recipients that received annual split inactivated influenza virus vaccination for 3 consecutive seasons. Specifically, the antibody serological and memory B-cell compartments were profiled for reactivity against current and historical influenza A virus strains. Moreover, multiparametric analysis and antibody landscape profiling revealed a transient increase in strain-specific antibodies in the elderly, but with an impaired recall response of pre-existing memory B-cells, plasmablast (PB) differentiation and long-lasting serological changes. This study thoroughly profiles and compares the immune response to recurrent influenza virus vaccination in young and elderly participants unveiling the pitfalls of current influenza virus vaccines in high-risk populations.

Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario.

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.

Seasonal influenza vaccination does not effectively expand H2 cross-reactive antibodies in humans.

Influenza viruses cause millions of infections and hundreds of thousands of deaths every year. Influenza virus vaccinations are produced every year and contain H1N1 and H3N2 influenza A viruses and either one or two influenza B viruses. In this study, we examined the effects of seasonal influenza vaccinations in people on both circulating serum antibody titers and memory B-cell activation to H2Nx influenza viruses. In addition to evaluating the human cohort as a whole, participants were also divided into three separate groups based upon their likelihood of being either exposed to or imprinted with H2N2 influenza viruses in the 1950s and 1960s. While participants born after H2N2 influenza viruses left the human population had lower HAI, ELISA and neutralizing antibody titers to these viruses, a select number of cross-reactive antibodies to some of the H2 HA proteins were boosted after seasonal influenza vaccination. However, these results varied and were not consistent by age group or specific H2 HA protein. Overall, seasonal influenza vaccination did not significantly expand cross-reactive antibodies to H2 HA antigens.

Functional characterization of SARS-CoV-2 vaccine elicited antibodies in immunologically naïve and pre-immune humans.

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.

SARS-CoV-2 mRNA Vaccines Elicit Different Responses in Immunologically Naïve and Pre-Immune Humans.

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.

Convergent antibody evolution and clonotype expansion following influenza virus vaccination.

Recent advances in high-throughput single cell sequencing have opened up new avenues into the investigation of B cell receptor (BCR) repertoires. In this study, PBMCs were collected from 17 human participants vaccinated with the split-inactivated influenza virus vaccine during the 2016-2017 influenza season. A combination of Immune Repertoire Capture (IRCTM) technology and IgG sequencing was performed on ~7,800 plasmablast (PB) cells and preferential IgG heavy-light chain pairings were investigated. In some participants, a single expanded clonotype accounted for ~22% of their PB BCR repertoire. Approximately 60% (10/17) of participants experienced convergent evolution, possessing public PBs that were elicited independently in multiple participants. Binding profiles of one private and three public PBs confirmed they were all subtype-specific, cross-reactive hemagglutinin (HA) head-directed antibodies. Collectively, this high-resolution antibody repertoire analysis demonstrated the impact evolution can have on BCRs in response to influenza virus vaccination, which can guide future universal influenza prophylactic approaches.

Portuguese Football Federation consensus statement 2020: nutrition and performance in football.

Nutrition is an undeniable part of promoting health and performance among football (soccer) players. Nevertheless, nutritional strategies adopted in elite football can vary significantly depending on culture, habit and practical constraints and might not always be supported by scientific evidence. Therefore, a group of 28 Portuguese experts on sports nutrition, sports science and sports medicine sought to discuss current practices in the elite football landscape and review the existing evidence on nutritional strategies to be applied when supporting football players. Starting from understanding football's physical and physiological demands, five different moments were identified: preparing to play, match-day, recovery after matches, between matches and during injury or rehabilitation periods. When applicable, specificities of nutritional support to young athletes and female players were also addressed. The result is a set of practical recommendations that gathered consensus among involved experts, highlighting carbohydrates periodisation, hydration and conscious use of dietary supplements.