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COVID-19 has spread and developed into a pandemic disease, forcing countries to impose challenging protocols and lockdowns. This study assessed shopping, food consumption behavior, and feelings in Jordan and several Arab countries during the COVID-19 pandemic. A cross-sectional web-based survey among the Middle East population was conducted using an online questionnaire between July and September 2022. Participants were requested to answer a standardized and validated structured questionnaire. Demographic information, shopping behavior information, and mental health data were requested. A total of 542 respondents were included in the study. During COVID-19 quarantine, participants (68.6%) reported decreased shopping frequency and buying more food than usual (37.5%). Cereals and legumes were the primary food types stored by participants (76.9%). Multiple logistic regression revealed the age of the participant as a significant factor affecting storing of food (being ≤ 25 years old (OR = 0.456, p value = 0.038)). 75.7% of female participants eat less frequently in restaurants than usual. In contrast, among males, 48.5% reported that they eat at restaurants less frequently than usual. The country of residency and gender were the significant factors affecting negative feelings and emotions. Participants in countries other than Jordan had a higher negative feeling score (Beta = 0.086, p value = 0.042). Furthermore, females had a higher negative feeling score (Beta = -0.128, p value = 0.003) as the negative feelings score for females was 3.58 (SD = 5.443). On the other hand, it was 2.10 (SD = 5.091) for males. The COVID-19 pandemic has altered Jordanians' attitudes, shopping, and food consumption habits. Although positive behaviors have improved, such as shopping less frequently, eating home-cooked meals, and dining with family, frequent snacking and food storage have increased. Finally, public awareness of shopping and food consumption habits should be promoted.

BACKGROUND AND PURPOSE: Spasticity (hypertonicity) is a frequent problem that can develop after stroke and can lead to a number of secondary complications, such as contractures and pain. Consequently, many rehabilitation resources are used in treating the condition and its secondary complications. At present, the clinical assessment of spasticity incorporates descriptive scales of resistance to passive movement, but the use of a neurophysiological measure of muscle activity levels has been advocated. This case report focuses on the diagnosis of spasticity through the use of a neurophysiological measure. CASE DESCRIPTION: . Two individuals who required botulinum toxin treatment for poststroke spasticity were assessed over a course of 20 weeks with both clinical (Modified Ashworth Scale) and neurophysiological (surface electromyography recording of levels of muscle activity) measures of spasticity. Additionally, arm function, arm movement, and pain were measured. The individuals' responses to treatment with botulinum toxin and overall recovery after stroke are described. OUTCOMES: There were discrepancies between the clinical and the neurophysiological measures of spasticity. The clinical measure of spasticity was not effective in consistently identifying the presence of spasticity and, therefore, also was ineffective in documenting the individuals' responses to treatment. The neurophysiological measure was able to identify when muscle activity levels had been reduced, but a reduction in muscle activity levels did not always correspond with a reduction in Modified Ashworth Scale scores. DISCUSSION: The accurate identification of spasticity is important not only for assessment but also for the selection of appropriate treatments after stroke. [ABSTRACT FROM AUTHOR]

This article aims to describe the specialty of 'physical and rehabilitation medicine' (PRM) in its European context and sets out to show the progress made over the last few years in its rapid development in Europe. It is expected to expand within the European Union (EU) following the accession of new member states and this article will discuss, in particular, the structure, role and the major issues facing the specialty in Europe. [ABSTRACT FROM AUTHOR]

PRIMARY OBJECTIVES: To follow-up a population of children admitted to one Hospital Trust with traumatic brain injury (TBI), and compare outcomes following mild TBI with outcomes following moderate or severe TBI. RESEARCH DESIGN: Population-based postal questionnaire survey. METHODS AND PROCEDURES: Questionnaires were mailed to parents of all 974 surviving children on a register of paediatric TBI admissions, 525 completed questionnaires were returned (56.2%). Most children (419) had suffered mild TBI, 57 moderate, and 49 severe. MAIN OUTCOMES AND RESULTS: Thirty per cent of parents received no information on post-injury symptoms, and clinical follow-up was limited. Statistically significant differences were observed between mild and moderate/severe groups for cognitive, social, emotional, and mobility problems. Nevertheless, approximately 20% of the mild group suffered from poor concentration, personality change and educational problems post-injury. Few schools (20%) made special provision for children returning after injury. CONCLUSIONS: Children can have long-lasting and wide-ranging sequelae following TBI. Information should be routinely given to parents and schools after brain injury. [ABSTRACT FROM AUTHOR]

Comments on the scope for rehabilitation in severely disabled stroke patients. Identification of the effectiveness and cost-effectiveness of rehabilitation; Management strategies for severely disabled stroke patients; Considerations on health, financial, moral and ethical issues.

Studies have shown that the expectations of physically disabled school leavers are low when they have nothing to do and they fail to develop even further. It has also been shown that where there is a service for young physically disabled school leavers, there is benefit for the young people. We performed an evaluation of our own service using a questionnaire and additionally looked at areas of unmet need. The study showed that the team's activities were useful, and young people obtained benefit from the service which they would not otherwise have had, for lack of proper assessment. It was realized that a number of services, which were requested, did not take place and these related to communication between our team and the community health service. We have adapted our service to address these problems and now plan to look more formally at ways to promote clients' desired lifestyles. [ABSTRACT FROM AUTHOR]

Abstract Background Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. Methods A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. Results The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. Conclusions Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today’s successful malaria control programmes.

Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)-specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers.

Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage-designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41-named "SOS"-and an isoleucine-to-proline point mutation-named "IP"-at residue 559) to induce precursor CD4 binding site (CD4bs)-targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line-targeting BG505 SOSIP GT1.1 ( n = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants ( n = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage-designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.

Vaccines incorporating slow delivery, multivalent antigen display, or immunomodulation through adjuvants have an important role to play in shaping the humoral immune response. Here we analyzed mechanisms of action of a clinically relevant combination adjuvant strategy, where phosphoserine (pSer)-tagged immunogens bound to aluminum hydroxide (alum) adjuvant (promoting prolonged antigen delivery to draining lymph nodes) are combined with a potent saponin nanoparticle adjuvant termed SMNP (which alters lymph flow and antigen entry into lymph nodes). When employed with a stabilized HIV Env trimer antigen in mice, this combined adjuvant approach promoted substantial enhancements in germinal center (GC) and antibody responses relative to either adjuvant alone. Using scRNA-seq and scBCR-seq, we found that the alum-pSer/SMNP combination both increased the diversity of GC B cell clones and increased GC B cell clonal expansion, coincident with increases in the expression of Myc and the proportion of S-phase GC B cells. To gain insight into the source of these changes in the GC response, we analyzed antigen biodistribution and structural integrity in draining lymph nodes and found that the combination adjuvant approach, but not alum-pSer delivery or SMNP alone, promoted accumulation of highly intact antigen on follicular dendritic cells, reflecting an integration of the slow antigen delivery and altered lymph node uptake effects of these two adjuvants. These results demonstrate how adjuvants with complementary mechanisms of action impacting vaccine biodistribution and kinetics can synergize to enhance humoral immunity.

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells., (© 2024 McIntire et al.)

The HIV-1 envelope glycoprotein (Env) is the sole neutralizing determinant on the surface of the virus. The Env gp120 and gp41 subunits mediate receptor binding and membrane fusion and are generated from the gp160 precursor by cellular furins. This cleavage event is required for viral entry. One approach to generate HIV-1 neutralizing antibodies following immunization is to express membrane-bound Env anchored on the cell-surface by genetic means using the natural HIV gp41 transmembrane (TM) spanning domain. To simplify the process of Env trimer membrane expression we sought to remove the need for Env precursor cleavage while maintaining native-like conformation following genetic expression. To accomplish these objectives, we selected our previously developed 'native flexibly linked' (NFL) stabilized soluble trimers that are both near-native in conformation and cleavage-independent. We genetically fused the NFL construct to the HIV TM domain by using a short linker or by restoring the native membrane external proximal region, absent in soluble trimers, to express the full HIV Env ectodomain on the plasma membrane. Both forms of cell-surface NFL trimers, without and with the MPER, displayed favorable antigenic profiles by flow cytometry when expressed from plasmid DNA or mRNA. These results were consistent with the presence of well-ordered cell surface native-like trimeric Env, a necessary requirement to generate neutralizing antibodies by vaccination. Inoculation of rabbits with mRNA lipid nanoparticles (LNP) expressing membrane-bound stabilized HIV Env NFL trimers generated tier 2 neutralizing antibody serum titers in immunized animals. Multiple inoculations of mRNA LNPs generated similar neutralizing antibody titers compared to immunizations of matched NFL soluble proteins in adjuvant. Given the recent success of mRNA vaccines to prevent severe COVID, these are important developments for genetic expression of native-like HIV Env trimers in animals and potentially in humans., Competing Interests: Authors PL and YT were employed by company Acuitas Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guenaga, Alirezaei, Feng, Alameh, Lee, Baboo, Cluff, Wilson, Bale, Ozorowski, Lin, Tam, Diedrich, Yates, Paulson, Ward, Weissman and Wyatt.)

Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design., (© 2024. The Author(s).)

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses against H1 predominantly targeted the central stem epitope in infected patients and vaccinated donors, whereas head epitopes were more prominently targeted on H3. Responses against H3 were less abundant, but a greater diversity of H3 epitopes were targeted relative to H1. While our analysis is limited by sample size, on average, vaccinated donors responded to a greater diversity of epitopes on both H1 and H3 than infected patients. These data establish a baseline for assessing polyclonal antibody responses in vaccination and infection, providing context for future vaccine trials and emphasizing the importance of carefully designing vaccines to boost protective responses towards conserved epitopes.

Monoclonal neutralizing antibodies (mAbs) are considered an important prophylactic against SARS-CoV-2 infection in at-risk populations and a strategy to counteract future sarbecovirus-induced disease. However, most mAbs isolated so far neutralize only a few sarbecovirus strains. Therefore, there is a growing interest in bispecific antibodies (bsAbs) which can simultaneously target different spike epitopes and thereby increase neutralizing breadth and prevent viral escape. Here, we generate and characterize a panel of 30 novel broadly reactive bsAbs using an efficient controlled Fab-arm exchange protocol. We specifically combine some of the broadest mAbs described so far, which target conserved epitopes on the receptor binding domain (RBD). Several bsAbs show superior cross-binding and neutralization compared to the parental mAbs and cocktails against sarbecoviruses from diverse clades, including recent SARS-CoV-2 variants. BsAbs which include mAb COVA2-02 are among the most potent and broad combinations. As a result, we study the unknown epitope of COVA2-02 and show that this mAb targets a distinct conserved region at the base of the RBD, which could be of interest when designing next-generation bsAb constructs to contribute to a better pandemic preparedness.

The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design., Competing Interests: Declaration of interests D.B.J., B.A.A., M.J.T.S., and W.J.M. were employees and shareholders of 10× Genomics, Inc., at the time this work was performed. D.B.J., B.A.A., M.J.T.S., and W.J.M. are inventors on patents in relation to algorithms, therapeutic candidates, and other components of this work. W.J.M. and D.B.J. are founders, employees, and shareholders of Infinimmune. B.B. is a shareholder of Infinimmune and a member of its scientific advisory board., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically in vivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication in vitro in primary human respiratory epithelial cell cultures and protected against IBV in vivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates., Competing Interests: Declaration of interests L.E.W. serves as a consultant for BigHat Biosciences. The content of this article is solely the responsibility of the authors and does not represent the official views of BigHat Biosciences. C.B.C. serves as a consultant to GlaxoSmithKline, Sanofi, TDCowen Investments, Guidepoint Global, Debiopharm, and CommenseBio and receives royalties from UpToDate. The laboratory of C.B.C. receives funding for unrelated work from Moderna. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, GlaxoSmithKline, and BTG International Inc; is a member of the Scientific Advisory Board of Meissa Vaccines; a former member of the Scientific Advisory Board of Gigagen (Grifols); and is founder of IDBiologics. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda, and IDBiologics during the conduct of the study. The opinions, interpretations, conclusions, and recommendations contained herein are those of the authors and are not necessarily endorsed by the US Department of Defense. E.D., T.E.E., and B.J.D. are employees of Integral Molecular, B.J.D. is a shareholder of Integral Molecular. Vanderbilt University has applied for a patent pertinent to some of the materials in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)